Vitamin D and COVID-19 Trial (VIVID)

• ClinicalTrials.gov Identifier: NCT04536298
• Recruitment Status: Not yet recruiting
• First Posted: September 2, 2020
• Last Update Posted: November 20, 2020
• Sponsor: Brigham and Women's Hospital
• Collaborators: Harvard Medical School; Harvard School of Public Health; Harvard Pilgrim Healthcare Institute; Fenway Health and Beth Israel Deaconess Medical Center; Tishcon Corporation; Takeda; Quest Diagnostics; Karolinska Institutet; Philanthropic donations
• Information provided by (Responsible Party): JoAnn E. Manson, MD, Brigham and Women's Hospital

Study Description

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 the risk of hospitalization and/or death in participants newly diagnosed with COVID-19, and reduces the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their closest household contacts (as documented by seroconversion).

Condition or disease	Intervention/treatment	Phase
COVID-19	Dietary Supplement: vitamin D; Dietary Supplement: Placebo	Phase 3

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 risk of hospitalization and/or death in people newly diagnosed with COVID-19, and reduces the risk of SARS-CoV-2 infection in their closest household contacts.

The trial will enroll 1500 individuals aged 30 or older who are newly diagnosed with COVID-19 ("index cases"), together with 1200 of their closest household contacts aged 18 or older (limited to at most one contact per household).

Following receipt of informed consent, all 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 their household contacts, 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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 2700 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Estimated Study Start Date: December 1, 2020
• Estimated Primary Completion Date: March 1, 2021
• Estimated Study Completion Date: March 1, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Vitamin D; Daily vitamin D3 (9600 IU/day on days 1 and 2; 3200 IU/day on days 3 through 28)	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
Placebo Comparator: Placebo; Placebo	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

Outcome Measures

Primary Outcome Measures :

1. Hospitalization or death in index cases [ Time Frame: 4 weeks ]

Secondary Outcome Measures :

1. 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
2. Time to hospitalization or death in index cases [ Time Frame: 4 weeks ]
3. ICU admission/ventilation support in index cases [ Time Frame: 4 weeks ]
4. SARS-CoV-2 infection in close household contacts [ Time Frame: 4 weeks ]
5. 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

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion/exclusion criteria for INDEX CASES:

Inclusion criteria

1. Adults aged 30 years or older who are newly diagnosed with COVID-19 infection within 72 hours of testing *AND* no more than 5 days from the onset of COVID-19-related symptoms.
2. Age-specific criteria: Age 30 to 49 years with 2 or more comorbidities (diabetes; hypertension; body mass index of 30 or greater; chronic obstructive pulmonary disease or emphysema: history of heart attack, stroke, coronary bypass surgery, coronary angioplasty or stent, hospitalization for heart failure; diagnosed sleep apnea) and/or risk factors (smoking; African American, Hispanic, Native American) *OR* Age 50 to 59 years with 1 or more comorbidities or risk factors *OR* Age 60 or older regardless of comorbidity or risk factor status.
3. 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 400 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. Known diagnosis of hypercalcemia or a condition associated with vitamin D hypersensitivity.
6. Prior diagnosis of cancer *AND* currently undergoing radiation, chemotherapy, or immunotherapy.
7. Kidney failure or dialysis; severe liver disease or cirrhosis.
8. Unstable, transient, or group (6 or more adults) living arrangement.
9. 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 as the index case and have been identified as the closest contact within that household.
2. Ability and willingness to understand and provide informed consent.

Exclusion criteria:

1. Known current pregnancy.
2. History of SARS-CoV-2 infection with onset of symptoms more than 6 days before study entry.
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 400 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. Known diagnosis of hypercalcemia or a condition associated with vitamin D hypersensitivity.
7. Prior diagnosis of cancer *AND* currently undergoing radiation, chemotherapy or immunotherapy.
8. Kidney failure or dialysis; severe liver disease or cirrhosis.
9. Unstable, transient, or group (6 or more adults) living arrangement.
10. Participation in other COVID-19 trials.

Contacts and Locations

Contacts

Contact: Trisha Copeland, MS, RD; 1-877-517-2555; pcopeland2@bwh.harvard.edu

Locations

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02215

Contact: Trisha Copeland, MS, RD 877-517-2555 pcopeland2@bwh.harvard.edu

Sponsors and Collaborators

Brigham and Women's Hospital

Harvard Medical School

Harvard School of Public Health

Harvard Pilgrim Healthcare Institute

Fenway Health and Beth Israel Deaconess Medical Center

Tishcon Corporation

Takeda

Quest Diagnostics

Karolinska Institutet

Philanthropic donations

Investigators

• Principal Investigator: JoAnn E Manson, MD, DrPH; Brigham and Women's Hospital
• Principal Investigator: Rui Wang, PhD; Harvard Medical School
• Principal Investigator: Davaasambuu Ganmaa, PhD; Harvard School of Public Health

More Information

Publications:

Manson JE, Bassuk SS. Commentary. Eliminating vitamin D deficiency during the COVID-19 pandemic: A call to action. Metabolism. 2020 Jul 23;112:154322. doi: 10.1016/j.metabol.2020.154322. [Epub ahead of print]

• Responsible Party: JoAnn E. Manson, MD, Professor of Medicine, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT04536298
• Other Study ID Numbers: 2020J-009152
• First Posted: September 2, 2020
• Last Update Posted: November 20, 2020
• Last Verified: November 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Details will be provided at a later date.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by JoAnn E. Manson, MD, Brigham and Women's Hospital:

COVID-19; SARS-CoV-2 infection; coronavirus; vitamin D; hospitalization; death; disease severity; treatment; prevention

Additional relevant MeSH terms:

Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents