Vitamin D and COVID-19 Trial
Vitamin D and COVID-19 Trial
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).
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.
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.