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Vitamin D and COVID-19 Trial (VIVID)

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ClinicalTrials.gov Identifier: NCT04536298
Recruitment Status : Recruiting
First Posted : September 2, 2020
Last Update Posted : June 14, 2021
Sponsor:
Collaborators:
Harvard Medical School (HMS and HSDM)
Harvard School of Public Health (HSPH)
Fenway Health and Beth Israel Deaconess Medical Center
Tishcon Corporation
Takeda
Quest Diagnostics-Nichols Insitute
Karolinska Institutet
Philanthropic donations
Information provided by (Responsible Party):
JoAnn E. Manson, MD, Brigham and Women's Hospital

Tracking Information
First Submitted Date  ICMJE August 27, 2020
First Posted Date  ICMJE September 2, 2020
Last Update Posted Date June 14, 2021
Actual Study Start Date  ICMJE December 28, 2020
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 2, 2021)
Rate of seeking healthcare visits (including hospitalizations, emergency room visits, or ambulatory or virtual clinician visits) for symptoms or concerns related to COVID-19 or deaths in participants newly diagnosed with COVID-19 (index cases) [ Time Frame: 4 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
Hospitalization or death in index cases [ Time Frame: 4 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 2, 2021)
  • Rate of hospitalization/death or emergency room visits related to COVID-19 infection among index cases [ Time Frame: 4 weeks ]
  • Rate of hospitalization/death or emergency room visits related to COVID-19 in index cases with high risk for disease progression (defined as age 50 or older, or age 18-49 with at least one co-morbidity or risk factor) [ Time Frame: 4 weeks ]
  • Self-reported disease severity in index cases [ Time Frame: 4 weeks ]
    Severity: 1=no COVID-19 illness; 2=COVID-19 illness with no hospitalization; 3=COVID-19 illness with hospitalization; or 4=death
  • Time to seeking healthcare (including hospitalizations, emergency room visits, or ambulatory or other clinician visits) or death in index cases [ Time Frame: 4 weeks ]
  • ICU admission/ventilation support in index cases [ Time Frame: 4 weeks ]
  • SARS-CoV-2 infection in close household contacts [ Time Frame: 4 weeks ]
    Seroconversion or other positive test
  • Time to symptom onset and self-reported disease severity in household contacts [ Time Frame: 4 weeks ]
    Severity: 1=no COVID-19 illness; 2=COVID-19 illness with no hospitalization; 3=COVID-19 illness with hospitalization; or 4=death
  • Rate of healthcare visits (including hospitalizations, emergency room visits, or ambulatory or other clinician visits) for symptoms or concerns related to COVID-19 infection or deaths among household contacts who contract COVID-19 [ Time Frame: 4 weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2020)
  • Self-reported disease severity in index cases [ Time Frame: 4 weeks ]
    Severity: 1=no COVID-19 illness; 2=COVID-19 illness with no hospitalization; 3=COVID-19 illness with hospitalization or death
  • Time to hospitalization or death in index cases [ Time Frame: 4 weeks ]
  • ICU admission/ventilation support in index cases [ Time Frame: 4 weeks ]
  • SARS-CoV-2 infection in close household contacts [ Time Frame: 4 weeks ]
  • Self-reported disease severity in close household contacts [ Time Frame: 4 weeks ]
    Severity: 1=no COVID-19 illness; 2=COVID-19 illness with no hospitalization; 3=COVID-19 illness with hospitalization or death
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vitamin D and COVID-19 Trial
Official Title  ICMJE A Cluster-Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Vitamin D3 Supplementation to Reduce Disease Severity in Persons With Newly Diagnosed COVID-19 Infection and to Prevent Infection in Household Members
Brief Summary The Vitamin D and COVID-19 Trial (VIVID) is a nationwide randomized clinical trial in 2700 U.S. men and women to investigate whether taking a daily dietary supplement of vitamin D for 4 weeks reduces disease severity in participants newly diagnosed with COVID-19, and reduces the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in household contacts of someone newly diagnosed with COVID-19 (as documented by seroconversion).
Detailed Description

Data from laboratory studies, epidemiologic research, and randomized clinical trials conducted in the pre-COVID era strongly suggest that vitamin D is active in pathways relevant to immune function and may reduce the risk of acute respiratory infections. More recently, some observational studies have shown a significant association between low vitamin D status and worse clinical outcomes among COVID-19 patients. Whether vitamin D supplementation can reduce the risk of adverse clinical outcomes in recently diagnosed COVID-19 patients and/or reduce risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) in those likely to have been exposed to the virus (post-exposure prophylaxis) is unknown.

The Vitamin D and COVID-19 Trial (VIVID) is a nationwide, pragmatic, cluster-randomized clinical trial in 2700 U.S. men and women investigating whether taking a daily dietary supplement of vitamin D3 for 4 weeks reduces the rate of seeking healthcare visits (including hospitalizations, emergency room visits, or ambulatory or virtual clinician visits) for symptoms or concerns related to COVID-19 or deaths in people newly diagnosed with COVID-19, and reduces the risk of SARS-CoV-2 infection and/or disease severity in household contacts of individuals newly diagnosed with COVID-19.

The trial will enroll 1500 individuals aged 18 or older who are newly diagnosed with COVID-19 ("index cases") and 1200 household contacts aged 18 or older.

Following receipt of informed consent, participants will be randomized -- i.e., assigned by chance (like a coin toss) -- to one of two groups: (1) daily vitamin D3 (9600 IU/day on days 1-2; 3200 IU/day on days 3-28) or (2) daily vitamin D placebo. Index cases and household contacts of an index case (limited to at most one contact per household), if any, will be assigned to the same group (cluster randomization). Participants will take three oral softgel capsules on day 1, three capsules on day 2, and one capsule each day on days 3 through 28. Participants will receive a 4-week supply of study capsules via overnight courier service.

Participants will fill out a short (15-20 minute) questionnaire each week during the 4-week pill-taking period, as well as a follow-up questionnaire at 8 weeks after randomization. These questionnaires ask about symptoms, general health, and use of medications and dietary supplements. Questionnaires will be completed online using a secure Internet-based system known as the Research Electronic Data Capture (REDCap) system. Participants must have an e-mail address to enroll in the study. Occasionally, participants (or their delegates) may receive a telephone call from study staff to collect information or to clarify answers on the questionnaire. Participants will be able to contact investigators or staff using a toll-free number, if they have any questions or need assistance.

Participants (or their delegates) who indicate on a study questionnaire that they have been hospitalized will be sent a medical release form to be signed and returned. The release form will be used to get medical records from the participant's physician or hospital to confirm the specific reason for the hospitalization. In the event of a participant's death, the participant's delegate will be sent a medical release form to be signed and returned. The release form will be used to get medical records from the participant's physician or hospital to confirm the specific cause of death.

Participants will provide dried blood spot samples at baseline and week 4. Participants will provide these samples using a sample collection kit mailed to their homes. Blood samples will be collected through a finger prick onto a filter paper. Blood samples will be stored and used to measure vitamin D (25(OH)D) levels. In participants who are not diagnosed with COVID-19 during the study, blood samples will be also be tested for COVID-19 antibodies.

Support for VIVID is provided by Harvard University and private philanthropy. Tishcon Corporation (Salisbury, Maryland, USA) is donating the study capsules. The Karolinska Institute (Stockholm, Sweden) is donating the serology assessment, and Quest Diagnostics (San Juan Capistrano, California, USA) is donating biomarker measurements.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE COVID-19
Intervention  ICMJE
  • Dietary Supplement: vitamin D
    Vitamin D softgel capsules; each capsule contains 3200 IU of vitamin D3. Three capsules per day (9600 IU/day) will be taken on days 1 and 2, and one capsule per day (3200 IU/day) will be taken on days 3 through 28
    Other Names:
    • vitamin D3
    • cholecalciferol
  • Dietary Supplement: Placebo
    Placebo softgel capsules. Three capsules per day will be taken on days 1 and 2, and one capsule per day will be taken on days 3 through 28
Study Arms  ICMJE
  • Active Comparator: Vitamin D
    Daily vitamin D3 (9600 IU/day on days 1 and 2; 3200 IU/day on days 3 through 28)
    Intervention: Dietary Supplement: vitamin D
  • Placebo Comparator: Placebo
    Placebo
    Intervention: Dietary Supplement: Placebo
Publications * Manson JE, Bassuk SS. Commentary. Eliminating vitamin D deficiency during the COVID-19 pandemic: A call to action. Metabolism. 2020 Nov;112:154322. doi: 10.1016/j.metabol.2020.154322. Epub 2020 Jul 23.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 1, 2020)
2700
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion/exclusion criteria for INDEX CASES:

Inclusion criteria

  1. Adults aged 18 years or older who are newly diagnosed with COVID-19 infection within 7 days of testing.
  2. Ability and willingness to understand and provide informed consent.

Exclusion criteria

  1. Known current pregnancy.
  2. Current hospitalization.
  3. Unable to complete online questionnaires or adhere to study requirements.
  4. Consume more than 1000 IU per day of vitamin D from all supplemental sources combined (individual vitamin D supplements, calcium plus vitamin D supplements, medications with vitamin D [e.g., Fosamax Plus D], and multivitamins) in the past 4 weeks.
  5. Use of prescription vitamin D treatments (Calcitriol [Rocaltrol, Calcitrol, Vectical, Calcijex] or Paricalcitol [Zemplar]).
  6. Consume supplements with more than 1200 mg calcium per day.
  7. Known diagnosis of hypercalcemia or a condition associated with vitamin D hypersensitivity.
  8. Prior diagnosis of cancer *AND* currently undergoing radiation, chemotherapy, or immunotherapy.
  9. Kidney failure or dialysis; severe liver disease or cirrhosis.
  10. Any parathyroid conditions.
  11. Use of medications for seizures or epilepsy. Examples: Carbamazepine (Carbatrol, Tegretol), Phenytoin (Dilantin, Phenytek), Valproic acid (Depakene), Oxcarbazepine (Oxtellar, Trileptal), Phenobarbital, Topiramate (Topamax).
  12. Use of digoxin.
  13. Inability to receive an overnight express mail shipment of study pills at a home address.
  14. Participation in other COVID-19 trials.

Inclusion/exclusion criteria for HOUSEHOLD CONTACTS:

Inclusion criteria:

  1. Persons aged 18 years or older who live in the same household with an index individual and have been identified as the closest household contact within the same household (limited to 1 per household).
  2. Persons aged 18 years or older who live in household with someone who tested positive for COVID-19 within past 7 days but not participating in VIVID.
  3. Ability and willingness to understand and provide informed consent.

Exclusion criteria:

  1. Known current pregnancy.
  2. History of SARS-CoV-2 infection.
  3. Receipt of a SARS-CoV-2 vaccination or monoclonal antibody.
  4. Unable to complete online questionnaires or adhere to study requirements.
  5. Consume more than 1000 IU per day of vitamin D from all supplemental sources combined (individual vitamin D supplements, calcium plus vitamin D supplements, medications with vitamin D [e.g., Fosamax Plus D], and multivitamins) in the past 4 weeks.
  6. Use of prescription vitamin D treatments (Calcitriol [Rocaltrol, Calcitrol, Vectical, Calcijex] or Paricalcitol [Zemplar]).
  7. Consume supplements with more than 1200 mg calcium per day.
  8. Known diagnosis of hypercalcemia or a condition associated with vitamin D hypersensitivity.
  9. Prior diagnosis of cancer *AND* currently undergoing radiation, chemotherapy, or immunotherapy.
  10. Kidney failure or dialysis; severe liver disease or cirrhosis.
  11. Any parathyroid condition.
  12. Use of medications for seizures or epilepsy. Examples: Carbamazepine (Carbatrol, Tegretol), Phenytoin (Dilantin, Phenytek), Valproic acid (Depakene), Oxcarbazepine (Oxtellar, Trileptal), Phenobarbital, Topiramate (Topamax).
  13. Use of digoxin.
  14. Inability to receive an overnight express mail shipment of study pills at a home address.
  15. Participation in other COVID-19 trials.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Trisha Copeland, MS, RD 1-877-517-2555 pcopeland2@bwh.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04536298
Other Study ID Numbers  ICMJE 2020P002815
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Details will be provided at a later date.
Responsible Party JoAnn E. Manson, MD, Brigham and Women's Hospital
Study Sponsor  ICMJE Brigham and Women's Hospital
Collaborators  ICMJE
  • Harvard Medical School (HMS and HSDM)
  • Harvard School of Public Health (HSPH)
  • Fenway Health and Beth Israel Deaconess Medical Center
  • Tishcon Corporation
  • Takeda
  • Quest Diagnostics-Nichols Insitute
  • Karolinska Institutet
  • Philanthropic donations
Investigators  ICMJE
Principal Investigator: JoAnn E Manson, MD, DrPH Brigham and Women's Hospital
Principal Investigator: Rui Wang, PhD Harvard Medical School (HMS and HSDM)
Principal Investigator: Davaasambuu Ganmaa, PhD Harvard School of Public Health (HSPH)
PRS Account Brigham and Women's Hospital
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP