Dietary Supplements for COVID-19

Phase 3

Terminated

• Conditions: Covid19
• Interventions: Drug: Vitamin D3 50,000 IU; Other: Microcrystalline Cellulose Capsule; Dietary Supplement: Vitamin C/Zinc; Other: Medium Chain Triglyceride Oil; Dietary Supplement: Vitamin K2/D

• Registration Number: NCT04780061
• Lead Sponsor: The Canadian College of Naturopathic Medicine

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-03-01
• Study First Submitted QC: 2021-03-01
• Study First Posted: 2021-03-03
• Study Start: 2021-07-12
• Primary Completion: 2022-05-03
• Study Completion: 2022-07-07
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-21
• Last Update Posted: 2022-10-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 90

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment	Vitamin D3 50,000 IU	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.
Control	Microcrystalline Cellulose Capsule	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
Treatment	Vitamin K2/D	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.
Treatment	Vitamin C/Zinc	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.
Control	Medium Chain Triglyceride Oil	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

Primary Outcome Measures

Name	Time	Method
Participant-reported Overall Health	During the intervention period (Daily for 21 days)	Measured using the EuroQol Visual Assessment Scale (EQ-VAS). Scores each day range from 0 (worst health imaginable) and 100 (best health imaginable). Scores summed over a 21-day period for a total range of 0-2100.

Secondary Outcome Measures

Name	Time	Method
Effect of COVID-19 on the Health Status of Participants	Baseline plus weeks 1, 2, 3, 4, 8, and 12	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 and 0 is the worst possible health.
Symptom Severity of Common COVID-19 Symptoms	During the intervention period (Daily for 21 days)	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. Scores converted into a number out of 100 and summed over 21 days for a range of 0-2100 where a higher score indicates a higher symptom severity (i.e., a worse outcome).
Total Symptom Duration	During the intervention period (21 days)	Measured as the time to a complete reduction of symptoms with no relapses (i.e., a 0 in all categories on the symptom questionnaire).
Incidence of Delayed Return to Usual Health	12 weeks	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 at least 12 weeks)
Number of Participants With a Hospital Visit or Admission	12 weeks	Includes ER visits, acute care admissions, and ICU admissions

Trial Locations

Locations (1)

The Centre for Health Innovation; 🇨🇦 Ottawa, Ontario, Canada