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Public PCR testing stopped in Ontario
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| Name | Class |
|---|---|
| Ottawa Hospital Research Institute | OTHER |
| Vitazan Professional | OTHER |
| New Roots Herbal | INDUSTRY |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vitamin D3 50,000 IU | Drug | 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. |
| 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). Scores summed over a 21-day period for a total range of 0-2100. | During the intervention period (Daily for 21 days) |
| 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 and 0 is the worst possible health. | Baseline plus weeks 1, 2, 3, 4, 8, and 12 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dugald Seely, ND, MSc | Canadian College of Naturopathic Medicine | Principal Investigator |
| Kumanan Wilson, MD, MSc | Ottawa Hospital Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Centre for Health Innovation | Ottawa | Ontario | K2P0M7 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37739466 | Derived | 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. | |
| 35241474 | Derived |
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Participants were enrolled from outpatient COVID-19 test centres associated with The Ottawa Hospital. The primary site for enrolment and coordination of the study was The Centre for Health Innovation, Ottawa, Canada with support from the Ottawa Hospital Research Institute.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment | Vitamin C 6g Oral Daily x 21 Days; Vitamin D3 50,000 IU Oral x1; Vitamin D3 1,000 IU Oral Daily x 21 Days; Vitamin K2 240 mcg Oral Daily x 21 Days; Zinc Acetate 75mg Oral Daily x 21 Days; |
| FG001 | Control | Placebo (Microcrystalline cellulose + medium chain triglyceride oil). Number of pills, frequency, and duration identical to treatment arm. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Participants only included if they began study treatments.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment | Vitamin C, Vitamin D3, Vitamin K2, Zinc |
| BG001 | Control | Placebo (Microcrystalline cellulose + medium chain triglyceride oil) |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Participants were included in the analysis of overall health, symptom severity, and symptom duration if they completed the 21-day intervention period, completed at least 11 (52%) daily assessments, and did not miss more than 3 assessments sequentially | Posted | Mean | Standard Deviation | score on a scale | During the intervention period (Daily for 21 days) |
|
During the intervention period (21 days) plus 1 additional week (4 weeks total)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Treatment | Vitamin C, Vitamin D3, Vitamin K2, Zinc | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ectopic Pregnancy | Pregnancy, puerperium and perinatal conditions | CTCAE (5.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | CTCAE (5.0) | Systematic Assessment |
Early termination leading to small number of subjects analyzed; Symptom severity and duration questionnaire not validated
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Coordinator | Patterson Institute for Integrative Oncology Research | 6137921222 | 1 | mlegacy@thechi.ca |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 3, 2021 | Feb 6, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 17, 2022 | Feb 6, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| C109691 | microcrystalline cellulose |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
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| Vitamin C/Zinc | 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. |
|
| Vitamin K2/D | Dietary 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 Capsule | Other | Placebo equivalent of Vitamin C/Zinc and Vitamin D3. |
|
| Medium Chain Triglyceride Oil | Other | Placebo equivalent of Vitamin K2/D |
|
| 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). | 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 at least 12 weeks) | 12 weeks |
| Number of Participants With a Hospital Visit or Admission | Includes ER visits, acute care admissions, and ICU admissions | 12 weeks |
| 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. |
| Lost to Follow-up |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Race data missing for 4 participants in the control arm | Count of Participants | Participants |
|
| Vaccination Status | Count of Participants | Participants |
|
| Comorbidities | Count of Participants | Participants |
|
| Other Variables | Count of Participants | Participants |
|
Placebo (Microcrystalline cellulose + medium chain triglyceride oil) |
|
|
|
| Secondary | 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. | Participants were included in this analysis if they completed a baseline questionnaire. | Posted | Mean | Standard Deviation | score on a scale | Baseline plus weeks 1, 2, 3, 4, 8, and 12 |
|
|
|
| Secondary | 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). | Participants were included in this analysis if they completed the 21-day intervention period, completed at least 11 (52%) daily assessments, and did not miss more than 3 assessments sequentially. | Posted | Mean | Standard Deviation | score on a scale | During the intervention period (Daily for 21 days) |
|
|
|
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| Secondary | 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). | Participants were included in this analysis if they completed the 21-day intervention period, completed at least 11 (52%) daily assessments, and did not miss more than 3 assessments sequentially. | Posted | Median | Full Range | Days | During the intervention period (21 days) |
|
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| Secondary | 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) | Participants were included in this analysis if they completed 12 weeks of follow-up. | Posted | Count of Participants | Participants | 12 weeks |
|
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| Secondary | Number of Participants With a Hospital Visit or Admission | Includes ER visits, acute care admissions, and ICU admissions | All participants who started the study drug were included in this analysis | Posted | Count of Participants | Participants | 12 weeks |
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| 44 |
| 0 |
| 44 |
| 16 |
| 44 |
| EG001 | Control | Placebo (Microcrystalline cellulose + medium chain triglyceride oil) | 0 | 46 | 1 | 46 | 6 | 46 |
| Abdominal Pain | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Heartburn | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Bloating | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Jaw Pain | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (5.0) | Systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
| Week 2 |
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| Week 8 |
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| Week 12 |
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| Intensive Care Unit Admissions |
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