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.
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
90
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.
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.
The Centre for Health Innovation
Ottawa, Ontario, Canada
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). Scores summed over a 21-day period for a total range of 0-2100.
Time frame: During the intervention period (Daily for 21 days)
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 and 0 is the worst possible health.
Time frame: 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. 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).
Time frame: 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).
Time frame: 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 at least 12 weeks)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
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 equivalent of Vitamin C/Zinc and Vitamin D3.
Placebo equivalent of Vitamin K2/D
Time frame: 12 weeks
Number of Participants With a Hospital Visit or Admission
Includes ER visits, acute care admissions, and ICU admissions
Time frame: 12 weeks