Dietary Supplements for COVID-19

Dietary Supplements to Reduce Symptom Severity and Duration in People With SARS-CoV-2: A Randomized, Double Blind, Placebo Controlled Clinical Trial

This is a double blind, placebo controlled, phase III randomized controlled trial evaluating the effects of the dietary supplements vitamin C, vitamin D, vitamin K, and zinc versus placebo on the overall health, symptom severity, and symptom duration of outpatients diagnosed with SARS-CoV-2.

Study Overview

• Status: Terminated
• Conditions: Covid19
• Intervention / Treatment: Drug: Vitamin D3 50,000 IU; Dietary supplement: Vitamin C/Zinc; Dietary supplement: Vitamin K2/D; Other: Microcrystalline Cellulose Capsule; Other: Medium Chain Triglyceride Oil

Detailed Description

This study proposed is a double-blind, placebo-controlled, phase III randomized controlled trial powered to detect meaningful differences in the overall health and symptom severity of people with COVID-19 between the treatment and control arms. Eligible participants will be randomly assigned, using a web randomization system, in a ratio of 1:1 to one of the following groups: (1) nutrient therapy with vitamin D, vitamin C, vitamin K2, and zinc or (2) placebo. Total trial duration will be 12 weeks. Nutrients or placebo will be given for a period of 21 days following enrolment and randomization. Total trial duration will be 12 weeks. Adverse events will be collected during the treatment phase plus one additional week (maximum 4 weeks).

With respect to the primary outcome of participant-reported overall health, power calculations were conducted based on between-group differences at a single time point (21 days) and Cohen's guideline for a small effect size of 0.3. A sample size of 176 (88 per arm) provides 80% power to detect a difference at an α of 0.05. To account for an approximate 10-15% lost to follow-up we will enrol 200 participants (100 per arm).

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K2P0M7
      • The Centre for Health Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adults (≥18) who test positive for SARS-CoV-2 in an outpatient setting
2. Access to internet

Exclusion Criteria:

1. Symptom onset greater than 4 days prior to enrolment
2. Supplementing regularly with >500 mg vitamin C, >1000 units vitamin D, >120 mcg vitamin K (any form), or >15 mg zinc taken daily within the past month
3. Currently taking warfarin or an equivalent vitamin K antagonist anticoagulant
4. End stage chronic kidney disease
5. History of calcium oxalate kidney stones
6. Active granulomatosis (sarcoidosis, tuberculosis, lymphoma)
7. Known hypercalcemia or hypervitaminosis D
8. Currently taking either of the following antibiotics: cephalexin, tetracyclines
9. Participating in an investigational study or participation in an investigational study within the past 30 days
10. Any reason which, under the discretion of the qualified investigator or delegate, would preclude the patient from participating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; Specific Product: Vitamin D3 50,000 IU Formulation: Capsule. Each capsule will contain 500 mg (50,000 units) cholecalciferol (vitamin D3) Dose: One capsule on day 1 of the intervention period Specific Product: Vitamin K2/D Formulation: Liquid. Each 0.0285 mL drop contains 30 mcg menaquinone-7 (MK-7, vitamin K2) and 3.125 mcg (125 units) cholecalciferol (vitamin D3). Dose: 0.114 mL (four drops) twice daily for 21 days totalling 240mcg MK-7 and 1,000 units cholecalciferol per day. Specific Product: Vitamin C/Zinc Formulation: Capsule. Each capsule will contain 666 mg ascorbic acid (vitamin C) and 8.3 mg of zinc acetate Dose: Three capsules three times daily for 21 days totalling 6 g ascorbic acid and 75 mg zinc acetate per day.	Drug: Vitamin D3 50,000 IU; This is a loading dose of Vitamin D. Vitamin D (cholecalciferol [vitamin D3]) is a fat-soluble vitamin that is synthesized following ultraviolet radiation to the skin, naturally occurs in a few dietary sources and is available as a dietary supplement.; Other Names: Cholecalciferol; Dietary supplement: Vitamin C/Zinc; This is a combination of Vitamin C and Zinc. Vitamin C (ascorbic acid, ascorbate) is a water-soluble vitamin that naturally occurs in many foods and is sold as a dietary supplement. It is required for the functioning of several enzymes and is important for the immune system. Zinc is one of the most abundant essential trace elements in the human body and is required for the function of several hundred enzymes and transcription factors.; Dietary supplement: Vitamin K2/D; This is a combination of Vitamin K2 (menaquinone-7) and vitamin D. Vitamin K (menaquinone-7 [vitamin K2]) is a fat-soluble vitamin found in foods and sold as a dietary supplement. Vitamin K plays a large role in synthesizing coagulation factors in the blood, and vitamin K deficiency has been associated with uncontrolled bleeding. Vitamin K1 (phylloquinone) is an alternate form of vitamin K found in foods and supplements; however, vitamin K2 has a better absorption profile50 and additionally plays a role in bone metabolism controlling the binding of calcium, especially in older adults, where it attenuates the rate of bone loss
Placebo Comparator: Control; Specific Product: Vitamin D3 50,000 IU Placebo Equivalent: microcrystalline cellulose capsule, 350 mg Specific Product: Vitamin K2/D Placebo Equivalent: Medium chain triglyceride oil Specific Product: Vitamin C/Zinc Placebo Equivalent: microcrystalline cellulose capsule, 350 mg	Other: Microcrystalline Cellulose Capsule; Placebo equivalent of Vitamin C/Zinc and Vitamin D3.; Other: Medium Chain Triglyceride Oil; Placebo equivalent of Vitamin K2/D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant-reported overall health	Measured using the EuroQol Visual Assessment Scale (EQ-VAS). Scores each day range from 0 (worst health imaginable) and 100 (best health imaginable).	During the intervention period (Daily for 21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of COVID-19 on the health status of participants	Measured using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire. Scores are converted into a unique health state. Health states are converted to an index value between 0 and 1, where 1 is considered the best possible health.	Baseline plus weeks 1, 2, 3, 4, 8, and 12
Symptom Severity of common COVID-19 symptoms	Measured using an internally-developed questionnaire. Includes fever, cough, shortness of breath, fatigue, headache, myalgia/arthralgia, nausea, vomiting, diarrhea, congestion, loss of taste, and loss of smell. Scores range from 0-3 for each symptom, totaling 0-42 for each day. 0 = no symptom, 1 = mild symptom, 2 = moderate symptom, 3 = severe symptom.	During the intervention period (Daily for 21 days)
Total symptom duration	Measured as the time to a complete reduction of symptoms with no relapses (i.e., a 0 in all categories on the symptom questionnaire).	During the intervention period (21 days)
Incidence of delayed return to usual health	Measured by the number of people experiencing "ongoing symptomatic COVID-19" (symptoms persisting between 4 and 12 weeks) and the number of people experiencing "post-COVID-19 syndrome" (symptoms persisting longer than 12 weeks)	12 weeks
Frequency of Hospitalizations	Includes ER visits, acute care admissions, and ICU admissions	12 weeks
Hospital Length of Stay	Number of days in acute care or ICU	12 weeks
All-cause mortality		12 weeks

Collaborators and Investigators

• Sponsor: The Canadian College of Naturopathic Medicine
• Collaborators: Ottawa Hospital Research Institute; Vitazan Professional; New Roots Herbal
• Investigators: Principal Investigator: Kumanan Wilson, MD, MSc, The Ottawa Hospital Research Institute

Publications and helpful links

General Publications

• Legacy M, Seely D, Conte E, Psihogios A, Ramsay T, Fergusson DA, Kanji S, Simmons JG, Wilson K. 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. BMJ Open. 2022 Mar 3;12(3):e057024. doi: 10.1136/bmjopen-2021-057024.

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Actual): May 3, 2022
• Study Completion (Actual): July 7, 2022

Study Registration Dates

• First Submitted: March 1, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 3, 2021

Study Record Updates

• Last Update Posted (Actual): October 25, 2022
• Last Update Submitted That Met QC Criteria: October 21, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; Vitamin D; COVID-19; Vitamin C; Zinc; Dietary Supplements; Natural Health Products; Vitamin K; NHP
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin D; Cholecalciferol; Vitamin K; Vitamins; Vitamin K 2
• Other Study ID Numbers: 20210072-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No