블랙시드 오일 (TQ)

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles.

1. Exp Biol Med (Maywood). 2015 Dec;240(12):1698-707. doi: 10.1177/1535370215579013. Epub 2015 Apr 28. The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles. Ali BH(1), Al Za'abi M(2), Shalaby A(3), Manoj P(1), Waly MI(4), Yas

Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model.

2. Oncotarget. 2014 Feb 15;5(3):634-48. doi: 10.18632/oncotarget.1596. Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model. Siveen KS(1), Mustafa N, Li F, Kannaiyan

Plants and Surgery: The Protective Effects of Thymoquinone on Hepatic Injury-A Systematic Review of In Vivo Studies.

3. Int J Mol Sci. 2018 Apr 5;19(4):1085. doi: 10.3390/ijms19041085. Plants and Surgery: The Protective Effects of Thymoquinone on Hepatic Injury-A Systematic Review of In Vivo Studies. Tekbas A(1), Huebner J(2), Settmacher U(3), Dahmen U(4). Author information: (1)Department of General, Visceral

A randomized, double-blind, placebo-controlled study to evaluate the benefits of a standardized Nigella sativa oil containing 5% thymoquinone in reducing the symptoms of seasonal allergy.

1. Medicine (Baltimore). 2024 Aug 9;103(32):e39243. doi: 10.1097/MD.0000000000039243. A randomized, double-blind, placebo-controlled study to evaluate the benefits of a standardized Nigella sativa oil containing 5% thymoquinone in reducing the symptoms of seasonal allergy. Majeed A(1), Majeed S(2), Parameswarappa AK(1), Murali A(1), Gudimallam S(1), Siddegowda C(3), Chandrashekar H(4), Mundkur L(1). Author information: (1)Sami-Sabinsa Group Limited, Bangalore, Karnataka, India. (2)Sabinsa Corporation, East Windsor, NJ. (3)Medstar Speciality Hospital, Bangalore, Karnataka, India. (4)BGS Global Institute of Medical Science Sunkalpalya, Bengaluru, Karnataka, India. BACKGROUND: Allergic rhinitis (AR) or seasonal allergy characterized by sneezing, nasal congestion, nasal itching, and nasal discharge, triggered by immune reactions to environmental allergens. Present day customers also monitor the personal improvements in the area of Evidence-Based natural medicines/supplements. METHODS: A randomized, double-blind, placebo-controlled study was conducted on 65 participants aged 18 to 60 years having 2 or more allergic symptoms like sneezing, rhinorrhoea, nasal obstruction, and nasal itching for a cumulative period greater than 1 hour per day. The study participants received a capsule of NSO (250 mg) with 2.5 mg piperine (BioPerine) as a bioavailability enhancer or a placebo, twice a day, after food for 15 days. The primary objectives were evaluated by mean change in Total Nasal Symptom Score and the duration of AR symptoms per day from baseline to Day 15. Secondary endpoints were changes in Total Ocular Symptoms Score, AR symptom frequency and severity, serum Immunoglobulin E levels, and Patient Global Impression of Change scale. Adverse events were monitored throughout the study. RESULTS: Sixty-five patients were enrolled and all of them completed the study, N = 33 in NSO and N = 32 in placebo. A significant reduction in Total Nasal Symptom Score and Total Ocular Symptoms Score was observed in the NSO group compared to the placebo, highlighting the potential of NSO in alleviating AR symptoms. The episodes of AR symptoms per day and the frequency of symptoms in 24 hours reduced significantly in 15 days in both groups, but the extent of improvement was significantly higher in NSO compared to placebo. Improvement in Patient Global Impression of Change was also significantly better in NSO compared to the placebo. Serum Immunoglobulin E levels decreased in NSO but were not significantly different from placebo. No clinically significant changes were observed in vital signs, liver and renal function, lipid profile, hematology, fasting blood sugar, or urine analysis at the end of the study. CONCLUSION: The result of the study demonstrates that NSO 250 mg with 2.5 mg piperine is an effective and well-tolerated supplement for the management of AR symptoms. Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc. DOI: 10.1097/MD.0000000000039243 PMCID: PMC11315530 PMID: 39121267 [Indexed for MEDLINE] Conflict of interest statement: AM, SM, AKP, AM, SG and LM employees of Sami-Sabinsa Group Limited or Sabinsa Corporation. CS and HCS do not have any conflict of interest to declare. Nigellin® Amber is marketed by Sami-Sabinsa Group Limited and Sabinsa Corporation.

A crossover randomized controlled trial examining the effects of black seed (Nigella sativa) supplementation on IL-1β, IL-6 and leptin, and insulin parameters in overweight and obese women.

2. BMC Complement Med Ther. 2024 Jan 5;24(1):22. doi: 10.1186/s12906-023-04226-y. A crossover randomized controlled trial examining the effects of black seed (Nigella sativa) supplementation on IL-1β, IL-6 and leptin, and insulin parameters in overweight and obese women. Razmpoosh E(1)(2), Safi S(2)(3), Mazaheri M(4)(5), Khalesi S(6), Nazari M(7), Mirmiran P(8)(9), Nadjarzadeh A(10)(11). Author information: (1)Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (2)Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, 8915173160, Iran. (3)Faculty School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (4)Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (5)Mother and Newborn, Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (6)Appleton Institute & School of Health, Medical and Applied Sciences, Central Queensland University, Brisbane, Australia. (7)Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (8)Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. parvin.mirmiran@gmail.com. (9)Department of Nutrition and Clinical Dietetics, Faculty of Nutrition Sciences and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. parvin.mirmiran@gmail.com. (10)Research Center for Food Hygiene and Safety, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, 8915173160, Iran. azadehnajarzadeh@gmail.com. (11)Faculty School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. azadehnajarzadeh@gmail.com. BACKGROUND: Nigella sativa (NS) oil has been found to have advantageous benefits in the management of inflammation and obesity. This study investigated the effect of NS supplementation on blood mRNA expressions and serum levels of IL-1β, IL-6, leptin, and insulin concentrations in overweight/obese women. METHODS: In a crossover design, participants were randomized to receive either NS supplements(2000 mg/day) or placebo for 2 durations(8 weeks). With between-subject and within-subject components and interactions, a repeated-measure ANOVA model was used considering the treatment, time, and the carryover effects. Cohen's d(d) was used to measure the magnitude of the effects. RESULTS: Forty-six eligible participants were included. NS supplementation significantly reduced the mRNA expressions(d=-0.68, P = 0.03) and serum levels of IL-1β with medium-high effect sizes(d=-1.6, P < 0.001). Significant reductions with large effect sizes were observed in the gene expression and serum levels of IL-6(d=-1.8, d=-0.78, respectively; P < 0.01) and Leptin(d=-1.9, d=-0.89, respectively; P < 0.01, serum leptin P carryover < 0.001). Despite the meaningful carryover effect for serum leptin, results remained significant following the first intervention period analysis(P < 0.001). A significant but low effect size decrease in serum insulin was observed(d=-0.3, P = 0.02). CONCLUSIONS: The clinical significance of present findings regarding improvements in obesity-related pro-inflammatory markers must be interpreted with caution due to some observed medium-low effect sizes. TRIAL REGISTRATION: IRCT20180430039475N1 (Date:25/6/2018). © 2023. The Author(s). DOI: 10.1186/s12906-023-04226-y PMCID: PMC10768077 PMID: 38178093 [Indexed for MEDLINE] Conflict of interest statement: The authors declare no competing interests.

A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease.

3. J Transl Med. 2022 Aug 19;20(1):377. doi: 10.1186/s12967-022-03579-1. A new nutraceutical (Livogen Plus®) improves liver steatosis in adults with non-alcoholic fatty liver disease. Ferro Y(#)(1), Pujia R(#)(1), Mazza E(1), Lascala L(2), Lodari O(2), Maurotti S(2), Pujia A(1)(3), Montalcini T(4)(5). Author information: (1)Department of Medical and Surgical Science, University Magna Græcia, 88100, Catanzaro, Italy. (2)Department of Clinical and Experimental Medicine, University Magna Greæcia, Catanzaro, Italy. (3)Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Græcia, 88100, Catanzaro, Italy. (4)Department of Clinical and Experimental Medicine, University Magna Greæcia, Catanzaro, Italy. tmontalcini@unicz.it. (5)Research Center for the Prevention and Treatment of Metabolic Diseases (CR METDIS), University Magna Græcia, 88100, Catanzaro, Italy. tmontalcini@unicz.it. (#)Contributed equally BACKGROUND: Currently, there is no approved medication for non-alcoholic fatty liver disease management. Pre-clinical and clinical studies showed that several bioactive molecules in plants or foods (i.e., curcumin complex, bergamot polyphenol fraction, artichoke leaf extract, black seed oil, concentrate fish oil, picroliv root, glutathione, S-adenosyl-L-methionine and other natural ingredients) have been associated with improved fatty liver disease. Starting from these evidences, our purpose was to evaluate the effects of a novel combination of abovementioned nutraceuticals as a treatment for adults with fatty liver disease. METHODS: A total of 140 participants with liver steatosis were enrolled in a randomized, double-blind, placebo controlled clinical trial. The intervention group received six softgel capsules daily of a nutraceutical (namely Livogen Plus®) containing a combination of natural bioactive components for 12 weeks. The control group received six softgel capsules daily of a placebo containing maltodextrin for 12 weeks. The primary outcome measure was the change in liver fat content (CAP score). CAP score, by transient elastography, serum glucose, lipids, transaminases, and cytokines were measured at baseline and after intervention. RESULTS: After adjustment for confounding variables (i.e., CAP score and triglyceride at baseline, and changes of serum γGT, and vegetable and animal proteins, cholesterol intake at the follow-up), we found a greater CAP score reduction in the nutraceutical group rather than placebo (- 34 ± 5 dB/m vs. - 20 ± 5 dB/m, respectively; p = 0.045). The CAP score reduction (%) was even greater in those with aged 60 or less, low baseline HDL-C, AST reduction as well as in men. CONCLUSION: Our results showed that a new combination of bioactive molecules as nutraceutical was safe and effective in reducing liver fat content over 12 weeks in individuals with hepatic steatosis. Trial registration ISRCTN, ISRCTN70887063. Registered 03 August 2021-retrospectively registered, https://doi.org/10.1186/ISRCTN70887063. © 2022. The Author(s). DOI: 10.1186/s12967-022-03579-1 PMCID: PMC9392294 PMID: 35986358 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no competing interests.

The effect of Nigella sativa on TAC and MDA in obese and overweight women: secondary analysis of a crossover, double blind, randomized clinical trial.

4. J Diabetes Metab Disord. 2022 Feb 7;21(1):171-179. doi: 10.1007/s40200-021-00954-5. eCollection 2022 Jun. The effect of Nigella sativa on TAC and MDA in obese and overweight women: secondary analysis of a crossover, double blind, randomized clinical trial. Abdollahi N(1)(2), Nadjarzadeh A(1)(2), Salehi-Abargouei A(1)(2), Fallahzadeh H(3), Razmpoosh E(4), Lorzaedeh E(5), Safi S(1)(2). Author information: (1)Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (2)Department of Nutrition, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (3)Research Center of Prevention and Epidemiology of Non Communicable Disease, Department of Biostatistics and Epidemiology, Faculty of Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (4)Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (5)School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, Australia. PURPOSE: Since obesity is a risk factor for various diseases and is associated with increased oxidative stress conditions, some herbs are considered to be effective in reducing obesity and its complications. METHODS: This secondary analysis investigates the effect of Nigella sativa (N.S) oil supplement on total antioxidant capacity (TAC) and malondialdehyde (MDA) levels in obese/overweight women. Obese and overweight healthy women were randomized to receive 2,000 mg/d of N.S supplement and placebo. The intervention periods lasted 8 weeks and were separated by a 4-week washout period. Also, each participant was given an iso-calorie diet. Baseline characteristics and TAC and MDA levels were measured. Pkcross analysis was performed for statistical analysis using Stata software. Also, Cohen's d was estimated as effect size for all results to assess the magnitude of the effects. RESULTS: 39 women completed the study. N.S oil supplementation at a dose of 2000 mg/d significantly increased serum TAC (P effect = 0.017, Cohen's d = 1.81) and reduced serum MDA (P effect < 0/001, Cohen's d =  - 0.32). CONCLUSION: Based on our findings taking N.S supplementation for 8 weeks can improve antioxidant conditions in obese and overweight adults. However, more studies with a larger population and the presence of both genders need to be done to confirm the results.Registration number: IRCT20180430039475N1. © Springer Nature Switzerland AG 2022. DOI: 10.1007/s40200-021-00954-5 PMCID: PMC9167332 PMID: 35673509 Conflict of interest statement: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest.

The effect of nigella sativa supplementation on cardiometabolic outcomes in patients with non-alcoholic fatty liver: A randomized double-blind, placebo-controlled trial.

5. Complement Ther Clin Pract. 2022 Aug;48:101598. doi: 10.1016/j.ctcp.2022.101598. Epub 2022 May 8. The effect of nigella sativa supplementation on cardiometabolic outcomes in patients with non-alcoholic fatty liver: A randomized double-blind, placebo-controlled trial. Rashidmayvan M(1), Vandyousefi S(2), Barati M(3), Salamat S(4), Ghodrat S(5), Khorasanchi M(6), Jahan-Mihan A(7), Nattagh-Eshtivani E(8), Mohammadshahi M(9). Author information: (1)Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. (2)Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA. (3)Department of Cellular and Molecular Nutrition, National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (4)Nutrition and Metabolic Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. (5)Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. (6)Student Research Committee, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran. (7)Department of Nutrition and Dietetics, University of North Florida, Jacksonville, FL, USA. (8)Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: nattagh.elyas@gmail.com. (9)Nutrition and Metabolic Disease Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: shahi334@gmail.com. BACKGROUND AND PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is one of the metabolic disturbances associated with liver cell inflammation. Nigella sativa (N.sativa) is a widely used medicinal plant known for its anti-inflammatory, antimicrobial, antioxidant, and hepato-protective properties. This study aimed to assess the effect of supplementation of N. sativa oil on plasma levels of adiponectin, leptin, and blood pressure (BP) in patients diagnosed with NAFLD. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled clinical trial was conducted on 44 NAFLD patients. Participants were randomly assigned to two groups (n = 22/group); the experimental group received 1000 mg of N. sativa oil per day, while the control group received a placebo for eight weeks. The primary outcome measures were serum levels of adiponectin, leptin, and systolic and diastolic blood pressure measured at the baseline and the end of the intervention. RESULTS: After eight weeks of supplementation with N. sativa oil, no statistically significant differences were found in serum levels of adiponectin (p = 0.40), leptin (p = 0.89), systolic BP (p = 0.13), and diastolic BP (p = 0.09) between the two groups. Furthermore, after supplementation with N. sativa, no significant changes were observed in leptin (p = 0.07), adiponectin (p = 0.13), systolic BP (p = 0.82), and diastolic BP (p = 0.38) within the two groups. CONCLUSION: These results indicate that administration of N. sativa oil 1000 mg/day for 8 weeks has no favorable effect on cardiometabolic measures in NAFLD patients. Further studies with higher dosage over a longer period are needed to investigate whether this effect is dose- and time-dependent. Copyright © 2022 Elsevier Ltd. All rights reserved. DOI: 10.1016/j.ctcp.2022.101598 PMID: 35567872 [Indexed for MEDLINE]

Effects of Nigella sativa supplementation on blood concentration and mRNA expression of TNF-α, PPAR-γ and adiponectin, as major adipogenesis-related markers, in obese and overweight women: a crossover, randomised-controlled trial.

6. Br J Nutr. 2022 May 11:1-10. doi: 10.1017/S0007114522001428. Online ahead of print. Effects of Nigella sativa supplementation on blood concentration and mRNA expression of TNF-α, PPAR-γ and adiponectin, as major adipogenesis-related markers, in obese and overweight women: a crossover, randomised-controlled trial. Razmpoosh E(1)(2), Safi S(2), Nadjarzadeh A(2), Salehi-Abargouei A(2), Mazaheri M(3)(4), Mirmiran P(5), Meyre D(6). Author information: (1)Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (2)Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (3)Department of Medical Genetics, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (4)Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (5)Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (6)Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada. Adipocyte expansion through adipogenesis can offset the adverse metabolic effects of obesity. Nigella sativa (NS) (black seed) oil is shown to have therapeutic features in the management of obesity. NS oil might have beneficial changes in obese populations through mediating serum levels of adipogenesis-related parameters and relative transcriptional gene-diet interactions (nutrigenomics), though no previous studies assessed this mechanism in overweight/obese participants. This study assessed the effects of NS oil supplements on blood concentration and mRNA expression levels of TNF-α, PPAR-γ and serum adiponectin and expression of AdipoR1, as major adipogenesis and obesity-related parameters, in overweight/obese women using a cross-over design. Eligible women were randomised to receive either NS oil supplements (2000 mg/d) or placebo. Two periods of interventions (8 weeks in each) were cross-changed by a 4-week washout period. An individualised diet plan without calorie deficits was given to participants to match their energy/macronutrient intakes. The Pkcross procedure and intention-to-treat analysis were performed using Stata. Cohen's d(d) was estimated to measure the magnitude of the effects. Forty-six participants were included. NS oil capsules reduced transcription levels ((d = -2·31), P < 0·001) and blood concentrations of TNF-α ((d = -0·29), P < 0·001). AdipoR1 expression (d = 2·24, P < 0·001) and serum adiponectin (d = 0·88, P < 0·001) showed a significant augmentation with a medium-high effect size, as did gene expression (d = 0·69, P < 0·001) and serum levels of PPAR-γ (d = 0·97, P < 0·001). There was a moderate but significant decrease in body weight (d = 0·6, P < 0·001). The present beneficial findings would provide strong information for future nutrigenomics/clinical trial studies assessing the role of NS in the management of obesity and other comorbidities. DOI: 10.1017/S0007114522001428 PMID: 35538630

Effects of repeated use of a commercial topical lotion on subcutaneous fat thickness in resistance-trained male athletes.

7. J Cosmet Dermatol. 2023 Jan;22(1):255-261. doi: 10.1111/jocd.14853. Epub 2022 Feb 28. Effects of repeated use of a commercial topical lotion on subcutaneous fat thickness in resistance-trained male athletes. Peos JJ(1), Ong J(1). Author information: (1)School of Human Sciences (Exercise and Sports Science), Faculty of Science, The University of Western Australia, Crawley, Western Australia, Australia. This study tested whether subcutaneous fat loss is enhanced via application of a popular topical fat loss lotion. Twenty resistance-trained men (mean ± SD age of 26.3 ± 6.3 years and weight of 86.8 ± 11.1 kg) had a topical fat-loss lotion containing Coleus forskholii, Silybin, Eucommia ulmoides leaf, Paullinia cupana seed, caffeine, and black pepper essential oil applied twice daily for 8 weeks to the front and lateral thigh of one of the participant's leg, and a placebo control lotion was applied to the same sites on the other leg. After 8 weeks, there were no significant differences between the placebo and treatment legs for the change in subcutaneous fat thickness of the front thigh (p = 0.73) or for leg fat percentage (p = 0.52). However, there was a slight, yet significant difference in the change in subcutaneous fat thickness of the lateral thigh favoring the treatment leg (-0.42 vs +0.75 mm, p = 0.029), but with this difference disappearing depending on the statistical tests being used. Only 2/19 participants perceived a difference in fat loss in response to each condition. Although the topical lotion tested here resulted in statistically significantly greater subcutaneous fat loss at the lateral but not front thigh, this effect was very small, contingent upon the statistical test being used, and unperceivable by the participants themselves. © 2022 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC. DOI: 10.1111/jocd.14853 PMCID: PMC10078737 PMID: 35174607 [Indexed for MEDLINE] Conflict of interest statement: We declare that no financial interest or benefit has arisen from the direct application of this research.

Effect of Nigella sativa supplementation on kidney function, glycemic control, oxidative stress, inflammation, quality of life, and depression in diabetic hemodialysis patients: study protocol for a double-blind, randomized controlled trial.

8. Trials. 2022 Feb 4;23(1):111. doi: 10.1186/s13063-021-05917-y. Effect of Nigella sativa supplementation on kidney function, glycemic control, oxidative stress, inflammation, quality of life, and depression in diabetic hemodialysis patients: study protocol for a double-blind, randomized controlled trial. Rahmani A(1), Maleki V(2), Niknafs B(3), Tavakoli-Rouzbehani OM(2), Tarighat-Esfanjani A(4)(5). Author information: (1)Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. (2)Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran. (3)Department of Internal Medicine, School of Medicine Imam Reza Medical Research and Training Hospital, Tabriz University of Medical Sciences, Tabriz, Iran. (4)Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran. tarighata@tbzmed.ac.ir. (5)Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. tarighata@tbzmed.ac.ir. BACKGROUND AND OBJECTIVES: The kidney is probably the most crucial target of microvascular damage in diabetes, which can ultimately eventuate end-stage renal disease (ESRD). Hemodialysis is the most usual way of renal replacement therapy in ESRD. Patients receiving hemodialysis are susceptible to many complications like hyperglycemia, inflammation, depression, anxiety, and poor quality of life. So, they are constrained to consume many drugs. Medicinal herbs are used in different cultures as a reliable source of natural remedies. This study aims to determine the efficacy of Nigella sativa (NS) oil supplementation on blood glucose, kidney function tests, inflammation, oxidative stress, quality of life, and depression in hemodialysis patients. METHODS AND ANALYSIS: This double-blind, randomized controlled trial will enroll 46 patients with diabetes mellitus who give hemodialysis thrice a week. Patients who have an inflammatory or infectious disease and who are receiving nonsteroidal anti-inflammatory drugs will be excluded. Patients will be randomized to the treatment and control group, which will be recommended using two soft gels of NS and paraffin oil, respectively. Laboratory tests will be assessed at baseline and end of the study, including fasting blood sugar, glycated albumin, insulin, creatinine, blood urea nitrogen, urea, uric acid, superoxide dismutase, malondialdehyde, total antioxidant capacity, high sensitive C reactive protein, and 24-h urine volume. Also, the kidney disease and quality of life and hospital anxiety and depression scale questionnaires will be evaluated. DISCUSSION: Previous studies have reported a positive effect of Nigella sativa supplementation in chronic kidney disease, but there is no evidence that this plant is safe in hemodialysis patients. The results of this study can be helpful in better control of blood sugar and kidney function and reduce complications in diabetic hemodialysis patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trials . Registered on 31 May 2020. © 2021. The Author(s). DOI: 10.1186/s13063-021-05917-y PMCID: PMC8815251 PMID: 35120579 [Indexed for MEDLINE] Conflict of interest statement: The Tabriz University of Medical Sciences funds this project. The funding body did not have any role in the design, collection, and analysis, writing of the manuscript, or submission of the manuscript for publication. The authors declare that they have no competing interests.

The effect of nanomicelle curcumin supplementation and Nigella sativa oil on the expression level of miRNA-21, miRNA-422a, and miRNA-503 gene in postmenopausal women with low bone mass density: A randomized, triple-blind, placebo-controlled clinical trial with factorial design.

9. Phytother Res. 2021 Nov;35(11):6216-6227. doi: 10.1002/ptr.7259. Epub 2021 Sep 8. The effect of nanomicelle curcumin supplementation and Nigella sativa oil on the expression level of miRNA-21, miRNA-422a, and miRNA-503 gene in postmenopausal women with low bone mass density: A randomized, triple-blind, placebo-controlled clinical trial with factorial design. Farshbaf-Khalili A(1), Farajnia S(2), Pourzeinali S(3), Shakouri SK(1), Salehi-Pourmehr H(4). Author information: (1)Physical Medicine and Rehabilitation Research Centre, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran. (2)Drug Applied Research Center, Tabriz University of Medical Science, Tabriz, Iran. (3)Health Center, Vice Chancellor for Health, Tabriz University of Medical Sciences, Tabriz, Iran. (4)Research Center for Evidence-based medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical, Tabriz, Iran. This study aimed to investigate the effect of nanomicelle curcumin (CUR), Nigella sativa oil (NS), and CUR and NS on the plasma levels of miR-21, miR-422a, and miR-503 expression in postmenopausal women with low bone mass density (BMD). This randomized, triple-blind, placebo-controlled clinical trial with a factorial design was conducted on 120 postmenopausal women from the integrated healthcare system, Tabriz-Iran. The BMD was determined using dual-energy X-ray absorptiometry (DEXA). Women were randomly divided into four groups of 30 participants: (a) CUR (80 mg) and placebo of NS, (b) NS (1,000 mg) and placebo of CUR, (c) CUR (80 mg) and NS (1,000 mg), and (d) both placebos (containing microcrystalline cellulose). The plasma level of miRNA-21, miRNA-422a, and miRNA-503 was determined by qRT-PCR. The expression level of miRNAs at the baseline was similar. At the end of the intervention, only the expression level of miRNA-21 changed statistically significantly between the four groups (p = .037) and between the NS and placebo groups (p = .005). Also, its expression in the two groups receiving NS (p = .037) and NS-CUR (p = .043) was significantly increased. NS and NS-CUR supplementation can increase the expression level of miRNA-21 in postmenopausal women with low bone density, and bring perspective to further studies of the target. © 2021 John Wiley & Sons Ltd. DOI: 10.1002/ptr.7259 PMID: 34496087 [Indexed for MEDLINE]

Effects of Nigella sativa oil supplementation on selected metabolic parameters and anthropometric indices in patients with coronary artery disease: A randomized, double-blind, placebo-controlled clinical trial.

10. Phytother Res. 2021 Jul;35(7):3988-3999. doi: 10.1002/ptr.7115. Epub 2021 Apr 13. Effects of Nigella sativa oil supplementation on selected metabolic parameters and anthropometric indices in patients with coronary artery disease: A randomized, double-blind, placebo-controlled clinical trial. Tavakoli-Rouzbehani OM(1)(2), Abbasnezhad M(3), Kheirouri S(4), Alizadeh M(2). Author information: (1)Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. (2)Nutrition Research Center, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. (3)Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. (4)Department of Clinical Nutrition, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran. Various metabolic parameters are risk factors related to the amplified risk of atherosclerotic cardiovascular disease. A wide variety of data exist on Nigella sativa (NS) and metabolic parameters. The current study is designed to examine NS supplementation on lipid profile, blood pressure, glycemic control, anthropometric indices, and insulin resistance in individuals with coronary artery disease (CAD). In a randomized, double-blind, placebo-controlled clinical trial, 60 patients with CAD received either 2 g of NS oil or sunflower oil as a placebo for 8 weeks. Biochemical and anthropometric measurements were assessed. NS significantly reduced weight (-1.82 Kg; 95% C, [2.72, 4.13]), body mass index (-0.67 kg/m2 ; 95% C, [0.33, 1.01]), waist circumference (-2.15 cm; 95% C, [1.06, 3.23]), hip circumference (-1.26 cm; 95% C, [0.61, 1.910]), waist-to-hip ratio (0.008; 95%C, [0.001, 0.01]), systolic (-9.52 mmHg; 95% C, [7.14, 11.9]), diastolic blood pressure (-8.26 mmHg; 95% C, [4.89, 11.62]), and fasting blood glucose (FBS) (-4.32 mg/dl; 95% C, [-0.51, 9.15]) as compared with the placebo group. The results indicate a potential beneficiary effect of NS on the metabolic parameters in CAD patients including improvements in anthropometric indices, blood pressure, and FBS. © 2021 John Wiley & Sons Ltd. DOI: 10.1002/ptr.7115 PMID: 33851461 [Indexed for MEDLINE]

The effect of nigella sativa on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials.

11. J Food Biochem. 2021 Apr;45(4):e13625. doi: 10.1111/jfbc.13625. Epub 2021 Feb 9. The effect of nigella sativa on biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials. Montazeri RS(1)(2), Fatahi S(1)(3), Sohouli MH(1)(2), Abu-Zaid A(4), Santos HO(5), Găman MA(6), Shidfar F(2). Author information: (1)Student Research Committee, Faculty of Public Health Branch, Iran University of Medical Sciences, Tehran, Iran. (2)Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran. (3)Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children's Health, Shahid Beheshti University of Medical sciences, Tehran, Iran. (4)Department of Pharmacology, College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN, USA. (5)School of Medicine, Federal University of Uberlandia (UFU), Uberlandia, Brazil. (6)"Carol Davila"University of Medicine and Pharmacy, Bucharest, Romania & Center of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest, Romania. Inflammation and oxidative stress are involved in the pathogenesis of a myriad of chronic disorders. This systematic review and meta-analysis was designed to determine the effects of Nigella Sativa (NS) seed and seed oil consumption on several biomarkers of inflammation and oxidative stress. The Scopus, Web of Science, and PubMed-MEDLINE databases were systematically searched until August 2019. The quality assessment and heterogeneity of the selected randomized clinical trials (RCTs) were measured using the Jadad checklist, and Q and I2 tests, respectively. Finally, a total of 10 clinical RCTs were found to be eligible for this meta-analysis. The pooled findings showed that NS consumption significantly reduced serum high-sensitivity C-reactive protein (hs-CRP; WMD: -0.67, 95% CI: -1.29, -0.05, I2  = 95.7%), tumor necrosis factor-alpha (TNF-α; WMD: -2.29, 95% CI: -4.48, -0.11, I2  = 93%), and malondialdehyde (MDA; WMD: -1.18, 95% CI: -2.24, -0.12, I2  = 85.4%), and significantly increased total antioxidant capacity (TAC; WMD: 0.35, 95% CI: 0.10, 0.59, I2  = 77.1%), and superoxide dismutase (SOD; WMD: 66.30, 95% CI: 1.03, 131.57, I2  = 99.4%) levels. Overall, the results of this systematic review and meta-analysis imply that NS consumption may decrease inflammatory response and oxidative stress markers. PRACTICAL APPLICATIONS: Overall, the evidence supports the consumption of NS to reduce hs-CRP, TNF-α, and MDA, and to increase SOD and TAC levels. In addition, the subgroup analyses findings concluded that lower dosages of NS, longer durations of the intervention, and the use of NS seed oil may result in more effective action on inflammatory markers, but because of the limited number of trials, the results must be analyzed with caution, especially for the subgroup analysis. However, further prospective studies regarding the effect of NS consumption on biomarkers of inflammation and oxidative stress, with larger sample sizes, from various countries and longer follow-up periods, are required to confirm whether NS possesses veritable anti-inflammatory and antioxidant effects. © 2021 Wiley Periodicals LLC. DOI: 10.1111/jfbc.13625 PMID: 33559935 [Indexed for MEDLINE]

The effect of Nigella sativa on appetite, anthropometric and body composition indices among overweight and obese women: A crossover, double-blind, placebo-controlled, randomized clinical trial.

12. Complement Ther Med. 2021 Mar;57:102653. doi: 10.1016/j.ctim.2020.102653. Epub 2020 Dec 25. The effect of Nigella sativa on appetite, anthropometric and body composition indices among overweight and obese women: A crossover, double-blind, placebo-controlled, randomized clinical trial. Safi S(1), Razmpoosh E(2), Fallahzadeh H(3), Mazaheri M(4), Abdollahi N(1), Nazari M(5), Nadjarzadeh A(6), Salehi-Abargouei A(1). Author information: (1)Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (2)Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (3)Research Center of Prevention and Epidemiology of Non Communicable Disease, Department of Biostatistics and Epidemiology, Health Faculty, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (4)Department of Medical Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Mother and Newborn, Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (5)Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (6)Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran; Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Electronic address: azadehnajarzadeh@gmail.com. OBJECTIVES: Obesity is a global concern which is associated with several complications and disease. DESIGN: Present study is the first crossover, double-blind, placebo-controlled, randomized clinical trial aimed to evaluate the effect of Nigella Sativa (N. sativa) intervention on anthropometric and body composition parameters as well as dietary intake and appetite in a crossover design. METHOD: Forty-five healthy women with obesity or overweight were randomized into two groups of intervention and placebo, and the study conducted in two 8-week periods of intervention separated by a 4-week washout period. Anthropometric and body composition indices and dietary intake were measured. Also, appetite sensation was evaluated via a standard visual analog scale (VAS) questionnaire. Pkcross procedure was performed for statistical analysis using STATA. Cohen's d effect size was estimated for all outcomes to determine the magnitude of the effects. RESULTS: Supplementation with 2000 mg of N. sativa oil found to have a considerable increment in the measures of body mass index (P < 0.001, Cohen's d = 0.5), body weight (P < 0.001, Cohen's d = 0.6) and waist circumference (P = 0.020, Cohen's d = 0.4) with a medium effect size measure, and a significant decrease in body fat mass (P = 0.019, Cohen's d = 0.2), body fat percent (P < 0.001, Cohen's d = 0.2) and visceral fat area (P = 0.011, Cohen's d = 0.2) with a small effect size measure. CONCLUSION: The overall improvements in anthropometric and body composition parameters and a significant decrease in appetite represents the beneficial effects of N. sativa supplements in the treatment of obesity. More studies with different dosages, a larger number of participants, and longer intervention duration are recommended to illustrate the exact effects of N. sativa as a complementary therapy for obesity. Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved. DOI: 10.1016/j.ctim.2020.102653 PMID: 33370571 [Indexed for MEDLINE]

Local Usage of Nigella sativa Oil as an Innovative Method to Attenuate Primary Dysmenorrhea: A Randomized Double-blind Clinical Trial.

13. Oman Med J. 2020 Sep 9;35(5):e167. doi: 10.5001/omj.2020.109. eCollection 2020 Sep. Local Usage of Nigella sativa Oil as an Innovative Method to Attenuate Primary Dysmenorrhea: A Randomized Double-blind Clinical Trial. Samadipour E(1), Rakhshani MH(2), Kooshki A(3), Amin B(4). Author information: (1)Department of Nursing, Sabzevar University of Medical Sciences, Sabzevar, Iran. (2)Department of Statistic, Sabzevar University of Medical Sciences, Sabzevar, Iran. (3)Non-Communicable Diseases Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran. (4)Cellular and Molecular Research Center, Department of Physiology and Pharmacology, Faculty of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran. OBJECTIVES: We sought to determine the effect of topical application of Nigella sativa (black seed) oil, on the primary dysmenorrhea intensity. METHODS: We conducted a randomized, double-blind clinical trial on 124 female students, 18-22 years old, living in the dormitories of Sabzevar Universities. After a primary assessment, participants were randomly divided into two groups. The first group rubbed two drops of N. sativa oil, and the second group rubbed liquid olive oil, as the placebo. Massage was performed on the fontanel lobe 3, at night, three days before menstruation, for eight consecutive days (about five days after menses). This procedure was repeated for three menstrual cycles. After three cycles, pain severity was measured by the visual analog scale. Data analysis was carried out using the Mann-Whitney U test and analysis of covariance (ANCOVA). RESULTS: This study was conducted on 124 female students. The mean age of students, mean age of first menarche, body mass index, and pain severity were not significantly different in the two groups (p > 0.050). No adverse effects were observed during the study. The results of ANCOVA showed that pain intensity in N. sativa oil group was significantly decreased compared to that of the placebo group (0.6 score; p < 0.050). CONCLUSIONS: N. sativa could be a promising, safe, and easily available analgesic supplement in women suffering from primary dysmenorrhea. The OMJ is Published Bimonthly and Copyrighted 2020 by the OMSB. DOI: 10.5001/omj.2020.109 PMCID: PMC7480012 PMID: 32953142

The effect of Nigella sativa supplementation on cardiovascular risk factors in obese and overweight women: a crossover, double-blind, placebo-controlled randomized clinical trial.

14. Eur J Nutr. 2021 Jun;60(4):1863-1874. doi: 10.1007/s00394-020-02374-2. Epub 2020 Sep 2. The effect of Nigella sativa supplementation on cardiovascular risk factors in obese and overweight women: a crossover, double-blind, placebo-controlled randomized clinical trial. Razmpoosh E(1)(2)(3), Safi S(1)(2), Nadjarzadeh A(1)(2), Fallahzadeh H(4), Abdollahi N(1)(2), Mazaheri M(5)(6), Nazari M(7), Salehi-Abargouei A(8)(9). Author information: (1)Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (2)Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (3)Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (4)Research Center of Prevention and Epidemiology of Non Communicable Disease, Department of Biostatistics and Epidemiology, Health Faculty, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (5)Department of Medical Genetics, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (6)Mother and Newborn, Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (7)Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. (8)Department of Nutrition, School of Public Health, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. abargouei@ssu.ac.ir. (9)Nutrition and Food Security Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. abargouei@ssu.ac.ir. PURPOSE: To assess the effect of Nigella sativa (N.S) oil supplements on CVD risk factors in a crossover design for the first time. METHODS: Obese and overweight healthy women were randomized to receive N.S oil (2000 mg/day) and placebo. This intervention period lasted for 8 weeks and separated by a 4-week washout period. An iso-caloric diet was given to every individual throughout the study. Blood pressure, lipid profile, atherogenic indices and liver enzymes were measured. Pkcross procedure was performed for statistical analyses using Stata software. Cohen's d was estimated as effect size for all outcomes to measure the magnitude of the effects. RESULTS: Thirty-nine participants completed the study. Capsules of N.S increased serum high-density lipoprotein cholesterol (Cohen's d = 0.47, P = 0.009), reduced low-density lipoprotein cholesterol (Cohen's d = - 0.33, P = 0.031), reduced TC/HDL-C ratio (as an atherogenic index, Cohen's d = - 0.9, P < 0.001), reduced serum glutamic-oxaloacetic transaminase (Cohen's d = 0- 0.5, P = 0.038) and reduced systolic blood pressure (Cohen's d = - 0.4, P < 0.001). There was no effect on diastolic blood pressure measures (P = 0.96). CONCLUSION: The overall improvements in cardiovascular disease (CVD) risk factors showed beneficial effects of N.S supplements among adults with obesity to prevent possible cardiovascular diseases. More studies with different designs and in other populations are suggested to clarify the exact effects of N.S as a complementary therapy for modulating CVD risk factors in individuals with overweight and obesity. TRIAL REGISTRATION: Iranian Registry of Clinical Trials, IRCT20180528039884N1, Registered on February 15th, 2019. DOI: 10.1007/s00394-020-02374-2 PMID: 32876804 [Indexed for MEDLINE]

Nigella sativa supplementation to treat symptomatic mild COVID-19: A structured summary of a protocol for a randomised, controlled, clinical trial.

15. Trials. 2020 Aug 8;21(1):703. doi: 10.1186/s13063-020-04647-x. Nigella sativa supplementation to treat symptomatic mild COVID-19: A structured summary of a protocol for a randomised, controlled, clinical trial. Koshak AE(1), Koshak EA(2), Mobeireek AF(3), Badawi MA(2), Wali SO(2), Malibary HM(2), Atwah AF(4), Alhamdan MM(5), Almalki RA(2), Madani TA(2). Author information: (1)Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia. aekoshak@kau.edu.sa. (2)Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. (3)Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. (4)Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia. (5)University Medical Services Centre, King Abdulaziz University, Jeddah, Saudi Arabia. OBJECTIVES: To investigate the potential efficacy of Nigella sativa (NS) oil supplementation on the outcomes of patients with mild Coronavirus Disease 2019 (COVID-19). TRIAL DESIGN: Prospective, two-arm, parallel-group, randomised (1:1 allocation ratio), open-label, controlled, exploratory phase II clinical trial of oral NS oil in patients with mild COVID-19. PARTICIPANTS: Inclusion Criteria: - Patients with mild COVID19 (defined as upper respiratory tract infection symptoms in the absence of clinical or radiological signs of pneumonia). - Adult (18 - 65 years old). - Written informed consent by the patient (or legally authorized representative) prior to initiation of any study procedures. - All patients should understand and agree to comply with planned study procedures. - Polymerase chain reaction (PCR)-confirmed infection with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) from throat swab. EXCLUSION CRITERIA: - Patients with pneumonia or severe illness requiring admission to intensive care unit. - Severe chronic kidney disease (i.e. estimated glomerular filtration rate [eGFR] < 30 mL / min ) or end stage renal disease requiring dialysis - Severe chronic liver disease (Alanine transaminase [AlT] or Aspartate transaminase [AST] > 5 times the upper limit of normal). - Pregnancy or breast feeding. - Anticipated transfer within 72 hours to another hospital that is not a study site. - Allergy to the study medication The trial is currently conducted on patients recruited from King Abdulaziz University Hospital, Jeddah, Saudi Arabia. INTERVENTION AND COMPARATOR: Intervention group: Nigella sativa oil (MARNYS® Cuminmar) 500 mg softgel capsules, one capsule orally twice daily for 10 days plus standard of care treatment (antipyretic, antitussive). Comparator group: standard of care treatment. MAIN OUTCOMES: Proportion of patients who clinically recovered (defined as 3 days of no symptoms) within 14 days after randomisation. RANDOMISATION: Patients will be randomly assigned to treatment or control groups in a 1:1 ratio using a computer-generated randomization scheme (Random permuted blocks of 10) developed using the web-based program: http://www.randomization.com . BLINDING (MASKING): No blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Up to 200 eligible patients will be randomly assigned to either treatment or control groups. TRIAL STATUS: Protocol version 1, as of July 14, 2020. Recruitment was started on May 21, 2020. The intended completion date is December 31, 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04401202 . Date of trial registration: May 26, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. DOI: 10.1186/s13063-020-04647-x PMCID: PMC7414256 PMID: 32771034 [Indexed for MEDLINE] Conflict of interest statement: The authors declare that they have no competing interests.