Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: study protocol for a randomised, double-blind, placebo controlled clinical trial

Mark Legacy, Dugald Seely, Ellen Conte, Athanasios Psihogios, Tim Ramsay, Dean A Fergusson, Salmaan Kanji, John-Graydon Simmons, Kumanan Wilson, Mark Legacy, Dugald Seely, Ellen Conte, Athanasios Psihogios, Tim Ramsay, Dean A Fergusson, Salmaan Kanji, John-Graydon Simmons, Kumanan Wilson

Abstract

Introduction: COVID-19 has caused morbidity, hospitalisations and deaths worldwide. Despite four approved vaccines for COVID-19 in Canada, there is still a need for effective treatments, especially for people in the community. Vaccine efficacy is not 100% and long-term efficacy is still unknown. Furthermore, there are challenges to herd immunity including vaccine hesitancy and underlying conditions preventing vaccination. We aim to explore if the nutrients vitamin C, vitamin D, vitamin K2 and zinc are an effective treatment option for outpatients diagnosed with COVID-19. The primary outcome is the difference in participant-reported overall health; secondary outcomes include the effect on health status, symptom severity and duration, frequency and length of hospitalisations and mortality.

Methods and analysis: This study is a two-arm, parallel-group, double-blind, placebo-controlled, phase III randomised controlled trial. 200 patients will be recruited remotely from COVID-19 test centres in Ottawa, Canada associated with The Ottawa Hospital. Overall health will be measured using the EuroQol Visual Assessment Scale; health status will be measured using the EuroQol 5-dimension 5-level questionnaire; symptom severity and duration will be measured using an independently developed questionnaire; analyses will use an area under the curve approach and compare mean scores using unadjusted t tests. Study data will be recorded on electronic case report forms using the Research Electronic Data Capture platform. An independent data safety and monitoring board will perform ongoing review of the study for feasibility and safety.

Ethics and dissemination: This study has received ethical approval from the research ethics boards of the Canadian College of Naturopathic Medicine and the Ottawa Health Sciences Network, as well as regulatory approval from the Therapeutic Products Directorate and Natural and Non-Prescription Health Products Directorate of Health Canada. Results will be published in a peer-reviewed scientific journal with open access.

Trial registration number: NCT04780061.

Keywords: COVID-19; clinical trials; complementary medicine.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

References

    1. Pascarella G, Strumia A, Piliego C, et al. . COVID-19 diagnosis and management: a comprehensive review. J Intern Med 2020;288:192–206. 10.1111/joim.13091
    1. World Health Organization . Weekly Epidemiological Update on COVID-19 - Edition 45 2021.
    1. Health Canada . Approved COVID-19 vaccines, 2021. Available: [Accessed 24 Jun 2021].
    1. Polack FP, Thomas SJ, Kitchin N. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;384:1576–7.
    1. Frederiksen LSF, Zhang Y, Foged C. The long road toward COVID-19 herd immunity: vaccine platform technologies and mass immunization strategies. Front Immunol 2020;1817:11.
    1. Health Canada . COVID-19 treatments 2021.
    1. Wang Y, Zhang D, Du G, et al. . Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569–78. 10.1016/S0140-6736(20)31022-9
    1. Beigel JH, Tomashek KM, Dodd LE. Remdesivir for the Treatment of Covid-19 - Preliminary Report. N Engl J Med 2020.
    1. Health Canada . Bamlanivimab for injection 2021.
    1. Health Canada . Product Monograph - Casirivimab and Imdevimab for Injection 2021.
    1. Michienzi SM, Badowski ME. Can vitamins and/or supplements provide hope against coronavirus? Drugs Context 2020;9. 10.7573/dic.2020-5-7. [Epub ahead of print: 22 06 2020].
    1. Beigmohammadi MT, Bitarafan S, Hoseindokht A, et al. . Impact of vitamins A, B, C, D, and E supplementation on improvement and mortality rate in ICU patients with coronavirus-19: a structured summary of a study protocol for a randomized controlled trial. Trials 2020;21:614. 10.1186/s13063-020-04547-0
    1. Hu X-Y, Wu R-H, Logue M, et al. . Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: a systematic review and meta-analysis. PLoS One 2017;12:e0181780. 10.1371/journal.pone.0181780
    1. Ding Y, Chen L, Wu W, et al. . Andrographolide inhibits influenza A virus-induced inflammation in a murine model through NF-κB and JAK-STAT signaling pathway. Microbes Infect 2017;19:605–15. 10.1016/j.micinf.2017.08.009
    1. Heinz SA, Henson DA, Austin MD, et al. . Quercetin supplementation and upper respiratory tract infection: a randomized community clinical trial. Pharmacol Res 2010;62:237–42. 10.1016/j.phrs.2010.05.001
    1. Pitt HA, Costrini AM. Vitamin C prophylaxis in marine recruits. JAMA 1979;241:908–11. 10.1001/jama.1979.03290350028016
    1. Hemilä H. Vitamin C and infections. Nutrients 2017;9. 10.3390/nu9040339. [Epub ahead of print: 29 Mar 2017].
    1. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013;1:Cd000980. 10.1002/14651858.CD000980.pub4
    1. Martineau AR, Jolliffe DA, Hooper RL, et al. . Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017;356:i6583. 10.1136/bmj.i6583
    1. Shimizu Y, Ito Y, Yui K, et al. . Intake of 25-hydroxyvitamin D3 reduces duration and severity of upper respiratory tract infection: a randomized, double-blind, placebo-controlled, parallel group comparison study. J Nutr Health Aging 2018;22:491–500. 10.1007/s12603-017-0952-x
    1. Jung H, Seo M-W, Lee S, et al. . Vitamin D3 supplementation reduces the symptoms of upper respiratory tract infection during winter training in vitamin D-Insufficient Taekwondo athletes: a randomized controlled trial. Int J Environ Res Public Health 2018;15:2003. 10.3390/ijerph15092003
    1. Science M, Johnstone J, Roth DE, et al. . Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 2012;184:E551–61. 10.1503/cmaj.111990
    1. Lau FH, Majumder R, Torabi R. Vitamin D insufficiency is prevalent in severe COVID-19. medRxiv 2020.
    1. Ohaegbulam KC, Swalih M, Patel P, et al. . Vitamin D supplementation in COVID-19 patients: a clinical case series. Am J Ther 2020;27:e485–90. 10.1097/MJT.0000000000001222
    1. Dofferhoff ASM, Piscaer I, Schurgers LJ. Reduced vitamin K status as a potentially modifiable prognostic risk factor for COVID-19. Clin Infect Dis 2021;73:e4039–404.
    1. Pal R, Banerjee M, Bhadada SK, et al. . Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis. J Endocrinol Invest 2022;45:53–68. 10.1007/s40618-021-01614-4
    1. Thomas S, Patel D, Bittel B, et al. . Effect of high-dose zinc and ascorbic acid supplementation vs usual care on symptom length and reduction among ambulatory patients with SARS-CoV-2 infection: the COVID A to Z randomized clinical trial. JAMA Netw Open 2021;4:e210369. 10.1001/jamanetworkopen.2021.0369
    1. Wiersinga WJ, Rhodes A, Cheng AC, et al. . Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19). JAMA 2020;324:782. 10.1001/jama.2020.12839
    1. EuroQol Group . EuroQol--a new facility for the measurement of health-related quality of life. Health Policy 1990;16:199–208. 10.1016/0168-8510(90)90421-9
    1. Tenforde MW, Kim SS, Lindsell CJ, et al. . Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020. MMWR Morb Mortal Wkly Rep 2020;69:993–8. 10.15585/mmwr.mm6930e1
    1. National Institute for Health and Care Excellence . COVID-19 rapid guideline: managing the long-term effects of COVID-19, 2020. Available: [Accessed 3 Jan 2021].
    1. US Food and Drug Admiinistration . Assessing COVID-19-RelatedSymptoms in outpatient adult and adolescent subjects in clinical trials of drugs and biological products for COVID-19 prevention or treatment: guidance for industry, 2020. Available:
    1. Palacios R, Patiño EG, de Oliveira Piorelli R, et al. . Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of treating Healthcare Professionals with the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac - PROFISCOV: A structured summary of a study protocol for a randomised controlled trial. Trials 2020;21:853. 10.1186/s13063-020-04775-4
    1. World Health Organization . Interim recommendations for use of the inactivated COVID-19 vaccine, CoronaVac, developed by Sinovac, 2020.

Source: PubMed

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