Covid19Phase 3NCT04780061
Dietary Supplements for COVID-19
A Phase 3 study testing Vitamin D3 50,000 IU, Vitamin C/Zinc and Vitamin K2/D in people with Covid19, run by The Canadian College of Naturopathic Medicine at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- Vitamin D3 50,000 IU, Vitamin C/Zinc and Vitamin K2/D
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteCanada
- Study dates
- 12 Jul 2021to 7 Jul 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (≥18) who test positive for SARS-CoV-2 in an outpatient setting
- Access to internet
Who cannot join
- Symptom onset greater than 4 days prior to enrolment
- 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
- Currently taking warfarin or an equivalent vitamin K antagonist anticoagulant
- End stage chronic kidney disease
- History of calcium oxalate kidney stones
- Active granulomatosis (sarcoidosis, tuberculosis, lymphoma)
Show all 10Show fewer
- Known hypercalcemia or hypervitaminosis D
- Currently taking either of the following antibiotics: cephalexin, tetracyclines
- Participating in an investigational study or participation in an investigational study within the past 30 days
- Any reason which, under the discretion of the qualified investigator or delegate, would preclude the patient from participating.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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).
- Conditions
- Covid19
- Being tested
- Vitamin D3 50,000 IU, Vitamin C/Zinc, Vitamin K2/D, Microcrystalline Cellulose Capsule, Medium Chain Triglyceride Oil
- Keywords
- Natural Health Products, NHP, Dietary Supplements, Vitamin C, Vitamin D, Vitamin K, Zinc, COVID-19, SARS-CoV-2
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin D3 50,000 IUDrug
Also called Cholecalciferol
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.
Vitamin C/ZincDietary 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.
Vitamin K2/DDietary supplement
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
Microcrystalline Cellulose CapsuleOther
Placebo equivalent of Vitamin C/Zinc and Vitamin D3.
Medium Chain Triglyceride OilOther
Placebo equivalent of Vitamin K2/D
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | 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. Receives: Drug: Vitamin D3 50,000 IU; Dietary Supplement: Vitamin C/Zinc; Dietary Supplement: Vitamin K2/D |
| Control | Placebo comparator | 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 Receives: Other: Microcrystalline Cellulose Capsule; Other: Medium Chain Triglyceride Oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During the intervention period (Daily for 21 days)
Secondary outcomes (5)
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.
Measured: 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).
Measured: 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).
Measured: 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)
Measured: 12 weeks
Number of Participants With a Hospital Visit or Admission
Includes ER visits, acute care admissions, and ICU admissions
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2021
- Study start12 Jul 2021
- Primary completion3 May 2022
- Study completion7 Jul 2022
Why it stopped: Public PCR testing stopped in Ontario
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Canadian College of Naturopathic Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Ottawa Hospital Research Institute, Vitazan Professional, New Roots Herbal
- Responsible party
- Sponsor
- Investigators
- Dugald Seely, ND, MSc, Principal investigator, Canadian College of Naturopathic MedicineKumanan Wilson, MD, MSc, Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04780061
- Sponsor's protocol ID
- 20210072-01H
- Status last verified
- Sep 2024
- First submitted
- 1 Mar 2021
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Seely D, Legacy M, Conte E, Keates C, 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: a double-blind randomised controlled trial. BMJ Open. 2023 Sep 22;13(9):e073761. doi: 10.1136/bmjopen-2023-073761.
PubMed 37739466Legacy 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.
PubMed 35241474
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Supplements to Reduce Symptom Severity and Duration in People With SARS-CoV-2: A Randomized, Double Blind, Placebo Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT04780061
- Acronym / sponsor ID
- 20210072-01H
- Conditions
- Covid19
- Keywords
- Natural Health Products, NHP, Dietary Supplements, Vitamin C, Vitamin D, Vitamin K, Zinc, COVID-19
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Public PCR testing stopped in Ontario
- Enrolment
- 90 participants (actual)
- Lead sponsor
- The Canadian College of Naturopathic MedicineUniversity, hospital or other
- Collaborators
- Ottawa Hospital Research Institute, Vitazan Professional, New Roots Herbal
- Study start
- 12 Jul 2021 (actual)
- Primary completion
- 3 May 2022 (actual)
- Study completion
- 7 Jul 2022 (actual)
- First posted
- 3 Mar 2021 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Vitamin D3 50,000 IU, Dietary Supplement: Vitamin C/Zinc, Dietary Supplement: Vitamin K2/DSpecific 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 | Placebo comparator | Other: Microcrystalline Cellulose Capsule, Other: Medium Chain Triglyceride OilSpecific 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adults (≥18) who test positive for SARS-CoV-2 in an outpatient setting
- Access to internet
Key exclusion criteria (10 listed)
- Symptom onset greater than 4 days prior to enrolment
- 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
- Currently taking warfarin or an equivalent vitamin K antagonist anticoagulant
- End stage chronic kidney disease
- History of calcium oxalate kidney stones
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D3 50,000 IUAlso: CholecalciferolThis 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. | Drug | Treatment |
| Vitamin C/ZincThis 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 | Treatment |
| Vitamin K2/DThis 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 | Dietary supplement | Treatment |
| Microcrystalline Cellulose CapsulePlacebo equivalent of Vitamin C/Zinc and Vitamin D3. | Other | Control |
| Medium Chain Triglyceride OilPlacebo equivalent of Vitamin K2/D | Other | Control |
Primary outcome
Participant-reported Overall Health
Time frame: 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.
5 secondary outcomes
Effect of COVID-19 on the Health Status of Participants
Time frame: Baseline plus weeks 1, 2, 3, 4, 8, and 12
Symptom Severity of Common COVID-19 Symptoms
Time frame: During the intervention period (Daily for 21 days)
Total Symptom Duration
Time frame: During the intervention period (21 days)
Incidence of Delayed Return to Usual Health
Time frame: 12 weeks
Number of Participants With a Hospital Visit or Admission
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37739466Seely D, Legacy M, Conte E, Keates C, 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: a double-blind randomised controlled trial. BMJ Open. 2023 Sep 22;13(9):e073761. doi: 10.1136/bmjopen-2023-073761.
- Derived from this study: PubMed 35241474Legacy 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dugald Seely, ND, MSc principal investigator
Canadian College of Naturopathic Medicine
Kumanan Wilson, MD, MSc principal investigator
Ottawa Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Vitamin D3 50,000 IU, Vitamin C/Zinc and Vitamin K2/D in people with Covid19, run by The Canadian College of Naturopathic Medicine at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participant-reported Overall Health (time frame: During the intervention period (Daily for 21 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04780061, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.