NCT04386850

Oral 25-hydroxyvitamin D3 and COVID-19

Status unknown Phase 2, PHASE3 Last updated 12 June 2020

What this trial tests

Phase 2, PHASE3 trial testing Oral 25-Hydroxyvitamin D3 in COVID 19 in 1,500 participants. Status unknown.

Timeline

14 April 2020

Primary endpoint
15 November 2020

15 March 2021

Quick facts

Lead sponsor	Tehran University of Medical Sciences
Phase	Phase 2, PHASE3
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	prevention
Enrollment	1,500
Start date	14 April 2020
Primary completion	15 November 2020
Estimated completion	15 March 2021
Sites	1 location across Iran

Drugs / interventions tested

• Oral 25-Hydroxyvitamin D3 — full drug profile →

Conditions studied

• COVID 19 — all drugs for COVID 19 →

Sponsor

Tehran University of Medical Sciences

Who can join

Adults 18 to 75, any sex, with COVID 19. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Immune-boosting role of vitamins D, C, E, zinc, selenium and omega-3 fatty acids: Could they help against COVID-19?
   Shakoor H, Feehan J, Al Dhaheri AS, Ali HI, et al · · 2021 · cited 206× · PMID 33308613 · DOI 10.1016/j.maturitas.2020.08.003
2. An update on drugs with therapeutic potential for SARS-CoV-2 (COVID-19) treatment.
   Drożdżal S, Rosik J, Lechowicz K, Machaj F, et al · · 2021 · cited 186× · PMID 34991982 · DOI 10.1016/j.drup.2021.100794
3. Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis.
   Rhodes JM, Subramanian S, Laird E, Griffin G, et al · · 2021 · cited 152× · PMID 32613681 · DOI 10.1111/joim.13149
4. Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166.
   Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R. · · 2020 · cited 113× · PMID 32535032 · DOI 10.1016/j.jsbmb.2020.105719
5. Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression.
   Beltrán-García J, Osca-Verdegal R, Pallardó FV, Ferreres J, et al · · 2020 · cited 103× · PMID 33003552 · DOI 10.3390/antiox9100936
6. Vitamin D supplementation for the treatment of COVID-19: a living systematic review.
   Stroehlein JK, Wallqvist J, Iannizzi C, Mikolajewska A, et al · · 2021 · cited 85× · PMID 34029377 · DOI 10.1002/14651858.cd015043
7. Treatment With 25-Hydroxyvitamin D₃ (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical
   Maghbooli Z, Sahraian MA, Jamalimoghadamsiahkali S, Asadi A, et al · · 2021 · cited 80× · PMID 34653608 · DOI 10.1016/j.eprac.2021.09.016
8. Races of small molecule clinical trials for the treatment of COVID-19: An up-to-date comprehensive review.
   Hu S, Jiang S, Qi X, Bai R, et al · · 2022 · cited 68× · PMID 34762760 · DOI 10.1002/ddr.21895