Oral 25-hydroxyvitamin D3 and COVID-19

• Status: Recruiting
• Trial end date: 2021-03-15
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Tehran University of Medical Sciences
• Collaborator: Boston University
• Treatments: Calcifediol; Hydroxycholecalciferols

Criteria

Inclusion Criteria:

1. Older than 18 years old and younger than 75 years old for all study groups.

2. Meet the diagnostic criteria of COVID-19 for different types (including ordinary type, heavy type and critical type) in infected patients.

3. No medications or disorders that would affect vitamin D metabolism

4. Women must be on birth control and not pregnant

5. Ability and willingness to give informed consent and comply with protocol requirements

Exclusion Criteria:

1. Ongoing treatment with pharmacologic doses of vitamin D, vitamin D metabolites or analogues

2. Pregnant or lactating women;

3. Severe underlying diseases, such as advanced malignant tumors, endstage lung disease, etc.

4. 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.

5. Chronic hepatic dysfunction, chronic kidney disease or intestinal malabsorption syndromes including inflammatory bowel disease.

6. Supplementation with over the counter formulations of vitamin D2 or vitamin D3

7. Use of tanning bed or artificial UV exposure within the last two weeks.

8. Consuming medication affecting vitamin D metabolism or absorption (anticonvulsants, anti-tuberculosis medication glucocorticoids, HIV medications and cholestyramine).

9. Subjects with a history of an adverse reaction to orally administered vitamin D, vitamin D metabolites or analogues.

10. 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.

11. Inability to give informed consent