Oral 25-hydroxyvitamin D3 and COVID-19
Preventive and Therapeutic Effects of Oral 25-hydroxyvitamin D3 on Coronavirus (COVID-19) in Adults
2 other identifiers
interventional
1,500
1 country
1
Brief Summary
The goal of this clinical trial is to investigate the therapeutic efficacy of rapidly correcting vitamin D deficiency in adults with the use of 25-hydroxyvitamin D3 \[25(OH)D3\] for reducing the risk of acquiring the SARS-CoV-2 (COVID-19) viral infection and mitigating morbidity and mortality associated with this infection. This evidence-based hypothesis is related to several observations. Macrophages, activated T and B lymphocytes have a vitamin D receptor and 1,25-dihydroxyvitamin D3 induces defensin protein synthesis, influences immunoglobulin production and modulates T-cell cytokine production and functions. 1,25-dihydroxyvitamin D3 also reduces the angiotensin-converting enzyme 2 (ACE2) that is believed to serve as the binding site and gateway for COVID-19 to become infectious. This is a multicenter randomized3 doubleblinded placebo-controlled study aimed at determining the benefits of 25(OH)D3 treatment for the prevention of COVID-19 infection and improving clinical outcomes in infected patients. The investigators plan to recruit 1500 subjects in 3 study groups that include hospital health providers, patients with a positive test for COVID-19 and their relatives with a negative test. Eligible subjects in each study group with a documented serum level of 25(OH)D \< 20 ng/mL will be randomized. Recruited subjects will be given 25 mcg of 25(OH)D3 daily or an identically appearing placebo at the time of randomization for two months. Three hospitals will participate and the sample size is foreseen to be equally distributed between the three. Since the clinical trial is designed as minimal risk a formal committee for data monitoring is not foreseen. However, potential toxicity will be monitored every 4 weeks with a serum calcium, albumin and creatinine by the PI and the study coordinators. If the corrected serum calcium increases above 10.6 mg/dl and a repeat confirms that the calcium is above 10.6 mg/dL the subject will be dropped from the study and referred to his or her PCP. Early signs and symptoms of vitamin D toxicity associated with hypercalcemia are increased thirst, increase in frequency of urination, especially at night. The subjects will be followed up weekly by phone to ask about their sign and symptoms.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2020
Shorter than P25 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 14, 2020
CompletedFirst Submitted
Initial submission to the registry
May 11, 2020
CompletedFirst Posted
Study publicly available on registry
May 13, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 15, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
March 15, 2021
CompletedJune 12, 2020
May 1, 2020
7 months
May 11, 2020
June 10, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
COVID-19 (SARA-Cov-2) infection
Percentage of patients with acute respiratory tract infection symptoms (e.g. fever, cough, dyspnea) with no other etiology that fully explains the clinical presentation accompanied by chest computed tomography (CT) scan findings compatible with Covid-19 or patients with a COVID-19 positive test by the polymerase chain reaction (PCR)
60 days
Severity of COVID-19 (SARA-Cov-2) infection
Percentage of mild, moderate and sever forms of COVID-19 based on WHO criteria
60 days
Hospitalization
Percentage of patients who need to be hospitalized
60 days
Disease duration
Days from the first symptom/positive test to discharge from hospital/negative test
60 days
Death
Rate of death due to COVID-19 during the study
60 days
Oxygen support
Percentage of COVID patients who need oxygen support
60 days
Secondary Outcomes (9)
Type of oxygen support
60 days
Symptoms of COVID-19
60 days
Serum Levels of 25-hydroxyvitamin D3
60 days
Serum levels of calcium
60 days
Serum levels of phosphorus
60 days
- +4 more secondary outcomes
Study Arms (2)
Treatment
EXPERIMENTALInfected patients with acute respiratory tract infection symptoms (e.g. fever, cough, dyspnea) with no other etiology that fully explains the clinical presentation accompanied by chest computed tomography (CT) scan findings compatible with Covid-19 or with a COVID-19 positive test by the polymerase chain reaction (PCR)
Prevention
EXPERIMENTALThis arm of study includes the health care providers and hospital workers with a negative test for COVID-19 and a close patient relative with a negative test for COVID-19 who lives with the infected patients.
Interventions
Subjects in the case group will receive 25 mcg of 25(OH)D3 once daily at bedtime for 2 months and the control group will receive placebo daily for 2 months.
Eligibility Criteria
You may qualify if:
- Older than 18 years old and younger than 75 years old for all study groups.
- Meet the diagnostic criteria of COVID-19 for different types (including ordinary type, heavy type and critical type) in infected patients.
- No medications or disorders that would affect vitamin D metabolism
- Women must be on birth control and not pregnant
- Ability and willingness to give informed consent and comply with protocol requirements
You may not qualify if:
- Ongoing treatment with pharmacologic doses of vitamin D, vitamin D metabolites or analogues
- Pregnant or lactating women;
- Severe underlying diseases, such as advanced malignant tumors, endstage lung disease, etc.
- History of elevated serum calcium \>10.6 mg/dl; that is corrected for albumin concentration or subjects with a history of hypercalciuria and kidney stones.
- Chronic hepatic dysfunction, chronic kidney disease or intestinal malabsorption syndromes including inflammatory bowel disease.
- Supplementation with over the counter formulations of vitamin D2 or vitamin D3
- Use of tanning bed or artificial UV exposure within the last two weeks.
- Consuming medication affecting vitamin D metabolism or absorption (anticonvulsants, anti-tuberculosis medication glucocorticoids, HIV medications and cholestyramine).
- Subjects with a history of an adverse reaction to orally administered vitamin D, vitamin D metabolites or analogues.
- Subjects with a history of conditions that can lead to high serum calcium levels such as sarcoidosis, tuberculosis and some lymphomas associated with activated macrophages which increase the production of 1,25(OH)2D.
- Inability to give informed consent
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Tehran University of Medical Scienceslead
- Boston Universitycollaborator
Study Sites (1)
Tehran University of Medical Sciences
Tehran, Iran
Related Publications (1)
Shakoor H, Feehan J, Al Dhaheri AS, Cheikh Ismail L, Ali HI, Alhebshi SH, Apostolopoulos V, Stojanovska L. Role of vitamin D supplementation in aging patients with COVID-19. Maturitas. 2021 Oct;152:63-65. doi: 10.1016/j.maturitas.2021.03.006. Epub 2021 Mar 16. No abstract available.
PMID: 33757717DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Mohamadali Sahraian, MD
Tehran University of Medical Sciences
- PRINCIPAL INVESTIGATOR
zhila Maghbooli, PhD
Tehran University of Medical Sciences
- PRINCIPAL INVESTIGATOR
Michael F Holick, PhD,MD
Boston University
- PRINCIPAL INVESTIGATOR
Arash Shirvani, MD, PhD
Boston University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- All subjects in a stratified random sampling method based on age, sex, BMI and serum level of 25(OH)D (\<10 ng/dL vs 10 to \<20 ng/dL) with serum calcium \<=10.6 mg/dL will be recruited in the 25(OH)D3 or placebo group. The clinical coordinator will determine this with a computer-generated randomization program. Subjects in the case group will receive 25 mcg of 25(OH)D3 once daily at bedtime for 2 months and the control group will receive placebo daily for 2 months.
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 11, 2020
First Posted
May 13, 2020
Study Start
April 14, 2020
Primary Completion
November 15, 2020
Study Completion
March 15, 2021
Last Updated
June 12, 2020
Record last verified: 2020-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- Beginning 9 month and ending 36 months following article publication.
- Access Criteria
- Investigators whose proposed use of the data has been approved by the current study principal investigators.
The datasets used and analyzed during the current study will be available from the Study Principal Investigators (zhilayas@gmeil.com) on reasonable request .