Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Oral 25-hydroxyvitamin D3 and COVID-19

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04386850
Recruitment Status : Recruiting
First Posted : May 13, 2020
Last Update Posted : May 13, 2020
Sponsor:
Collaborator:
Boston University
Information provided by (Responsible Party):
Tehran University of Medical Sciences

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. We 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.

Condition or disease Intervention/treatment Phase
COVID 19 Drug: Oral 25-Hydroxyvitamin D3 Phase 2 Phase 3

Detailed Description:
Improvement in the vitamin D status i.e. total serum 25-hydroxyvitamin D in children and adults has been associated with reduced risk of upper respiratory tract infections including influenza A infection. The rationale for giving 25(OH)D3 rather than vitamin D3 is to rapidly improve the vitamin D status of the subjects who are at high risk of acquiring COVID 19 or who are infected by this very aggressive viral infection. It takes approximately 6-8 weeks to achieve a steady state blood level of 25(OH)D when ingesting a daily dose of vitamin D3 whereas ingesting 25(OH)D3 results in a rapid rise in its blood level reaching steady state within 48 hours. Based on the available literature it is reasonable to consider the possibility that vitamin D deficiency could increase risk of acquiring COVID 19 infection and exacerbating its infectivity and the body's cytokine response to it. It therefore seems plausible that the rapid improvement in vitamin D status by providing 25(OH)D3 may contribute to reducing the severity of illness caused by COVID-19, particularly in settings where hypovitaminosis D is frequent especially in people of color. Arguably, there is little evidence to date that improving the vitamin D status will reduce the infectivity risk or mitigate the devastating health consequences of COVID-19 infection. The proposed study to rapidly improve vitamin D status in adults who are at high risk of acquiring COVID- 19 or who are at risk for its morbidity and mortality will test the veracity of this evidence based hypothesis. Results from this study, especially if positive, would have far reaching global health consequences. Vitamin D3, vitamin D2 and 25-hydroxyvitamin D3 are readily available worldwide and could be quickly instituted as a rapid cost-effective method to help combat this pandemic.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a multicenter randomized double-blinded placebo-controlled clinical trial with parallel groups and allocation 1:1.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Prevention
Official Title: Preventive and Therapeutic Effects of Oral 25-hydroxyvitamin D3 on Coronavirus (COVID-19) in Adults
Actual Study Start Date : April 14, 2020
Estimated Primary Completion Date : November 15, 2020
Estimated Study Completion Date : March 15, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Calcifediol

Arm Intervention/treatment
Experimental: Treatment
Infected patients with a positive test for COVID-19
Drug: Oral 25-Hydroxyvitamin D3
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.

Experimental: Prevention
This 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.
Drug: Oral 25-Hydroxyvitamin D3
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.




Primary Outcome Measures :
  1. COVID-19 (SARA-Cov-2) infection [ Time Frame: 60 days ]
    patients over 18 years of age 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 definite diagnosis of Covid-19 with real-time polymerase chain reaction (PCR)

  2. Severity of COVID-19 (SARA-Cov-2) infection [ Time Frame: 60 days ]
    Mild, moderate and sever based on WHO criteria

  3. Hospitalization [ Time Frame: 60 days ]
    Need to admission in Hospital

  4. Disease duration [ Time Frame: 60 days ]
    from first symptom/positive test to discharge from hospital/negative test

  5. Death [ Time Frame: 60 days ]
    The mortality of COVID-19 during the study

  6. Oxygen support [ Time Frame: 60 days ]
    Need to oxygen support


Secondary Outcome Measures :
  1. Type of oxygen support [ Time Frame: 60 days ]
    Nasal cannula, Non-invasive ventilation or high-flow nasal cannula, Invasive mechanical ventilation, Invasive mechanical ventilation and ECMO

  2. Symptoms of COVID-19 [ Time Frame: 60 days ]
    fever, dry cough, coughing sputum or blood, sore throat, headache, diarrhea and shortness of breath

  3. Serum Levels of 25-hydroxyvitamin D3 [ Time Frame: 60 days ]
    Serum Levels of 25-hydroxyvitamin D3 by HPLC

  4. Biochemical measurements [ Time Frame: 60 days ]
    serum levels of calcium, phosphorus, creatinine, albumin, BUN, LFTs, and PTH



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04386850


Contacts
Layout table for location contacts
Contact: zhila maghbooli, PhD +98 21 6670 6142 zhilayas@gmail.com
Contact: Arash shirvani hn@bu.edu

Locations
Layout table for location information
Iran, Islamic Republic of
Tehran University of Medical Sciences Recruiting
Tehran, Iran, Islamic Republic of
Contact: Zhila Maghbooli, PhD    +98 21 6670 6142    zhilayas@gmail.com   
Sponsors and Collaborators
Tehran University of Medical Sciences
Boston University
Investigators
Layout table for investigator information
Principal Investigator: Mohamadali Sahraian, MD Tehran University of Medical Sciences
Principal Investigator: zhila Maghbooli, PhD Tehran University of Medical Sciences
Layout table for additonal information
Responsible Party: Tehran University of Medical Sciences
ClinicalTrials.gov Identifier: NCT04386850    
Other Study ID Numbers: IRCT2020-0401046909N2
IRCT20200401046909N1 ( Registry Identifier: IRCT )
IRCT2020-0401046909N2 ( Registry Identifier: IRCT )
First Posted: May 13, 2020    Key Record Dates
Last Update Posted: May 13, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: The datasets used and analyzed during the current study will be available from the corresponding author on reasonable request.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tehran University of Medical Sciences:
COVID 19
Vitamin D
25-hydroxyvitamin D3
1,25-dihydroxyvitamin D3
Viral infection
Cytokine storm
supplementation
Clinical Trial
Health Care provider
Prevention
Treatment
Additional relevant MeSH terms:
Layout table for MeSH terms
Hydroxycholecalciferols
Calcifediol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents