Daily Vitamin D for Sickle-cell Respiratory Complications
Overview
- Phase
- Phase 2
- Intervention
- Daily oral vitamin D3, 3,333 IU
- Conditions
- Sickle Cell Disease
- Sponsor
- Columbia University
- Enrollment
- 58
- Locations
- 1
- Primary Endpoint
- Annual Rate of Respiratory Events
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
This study aims to answer the question whether daily oral vitamin D supplementation can reduce the risk of respiratory or lung complications in children and adolescents with sickle cell disease. Respiratory problems are the leading causes of sickness and of death in sickle cell disease. The investigators hypothesize that daily oral vitamin D3, compared to monthly oral vitamin D, will rapidly increase circulating vitamin D3, and reduce the rate of respiratory complications by 50% or more within the first year of supplementation in children and adolescents with sickle cell disease.
This study is funded by the FDA Office of Orphan Products Development (OOPD).
Detailed Description
This is a 2-year controlled, double-blind, randomized Phase 2 clinical trial comparing the efficacy in reducing the rate of respiratory events in sickle-cell disease of daily oral vitamin D3 (3,333 IU/d) with monthly bolus oral vitamin D3, (100,000 IU/mo) as a control. The scientific premise of the clinical trial is that circulating concentrations of vitamin D3, the parent compound, are the principal determinant of the anti-infective and immunomodulatory effects of supplementation. Eligible participants will be initially screened to determine their blood vitamin D levels. Those with 25-hydroxyvitamin D levels between 5 and 60 ng/mL will be assigned by chance to one of the two arms for 24 months. Participants will be checked every month and will have periodic blood and urine tests to monitor for any side effects of the study treatments. Children above 5 y/o who can cooperate and understand the procedure will have lung function test at baseline and at 24 months. Showing that a monthly dose of vitamin D reduces lung infections, asthma and the acute chest syndrome could help establish this simple, low-cost treatment as a way to decrease sickness and deaths in children and adolescents with sickle-cell disease.
Investigators
Margaret T. Lee
Professor of Pediatrics
Columbia University
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of sickle cell disease (Hb SS, Hb SC, Hb S-Beta-thalassemia)
- •Age 3-20 years old
Exclusion Criteria
- •Patient unwilling or unable to provide written informed consent (and assent, if applicable)
- •Patient unable or unwilling to comply with requirements of the clinical trial
- •Participation in another clinical trial
- •Current diagnosis of rickets
- •History of hypercalcemia or diagnosis of any medical condition associated with hypercalcemia, including primary hyperparathyroidism, malignancy, sarcoidosis, tuberculosis, granulomatous disease, familial hypocalciuric hypercalcemia
- •Current use of corticosteroids, excluding inhaled steroids
- •Current use of anticonvulsants (phenytoin, phenobarbital, carbamazepine)
- •Therapy with thiazide diuretics or lithium carbonate
- •Known liver or renal disease
- •Patients taking medications for pulmonary complications of sickle cell disease not on a stable dose of medications, as defined by a change in medications or doses within the three months prior to study entry
Arms & Interventions
Daily oral vitamin D3
Oral vitamin D3, 3,333 IU
Intervention: Daily oral vitamin D3, 3,333 IU
Monthly bolus oral vitamin D3
Bolus oral vitamin D3, 100,000 IU
Intervention: Monthly oral vitamin D3, 100,000 IU
Monthly bolus oral vitamin D3
Bolus oral vitamin D3, 100,000 IU
Intervention: Placebo oral tablet
Outcomes
Primary Outcomes
Annual Rate of Respiratory Events
Time Frame: Month 12, Month 24
Respiratory events will be calculated as the sum of respiratory infection, asthma exacerbation, and acute chest syndrome, as ascertained by use of a validated questionnaire.
Secondary Outcomes
- Mean Forced Vital Capacity (FVC % Predicted)(Baseline, Month 24)
- Forced Expiratory Volume in 1 Second (FEV1)(Baseline, Month 24)
- Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity Ratio(Baseline, Month 24)
- Forced Expiratory Flow at 25%-75% Vital Capacity (FEF25-75, % Predicted)(Baseline, Month 24)
- Ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)(Baseline, Month 24)
- Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)(Baseline, Month 24)
- Neutrophil Count(Baseline, Month 12, Month 24)
- Platelet Count(Baseline, Month 12, Month 24)
- Serum C-reactive Protein (CRP)(Baseline, Month 12, Month 24)