Vitamin D for Sickle-cell Respiratory Complications

Study Overview
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Brief Summary
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This study aims to answer the question whether oral vitamin D supplementation can decrease lung complications in children and adolescents with sickle cell disease. Lung complications are the leading causes of morbidity and of death in sickle cell disease. Infections and increased inflammation play important roles in the development of the lung problems in sickle cell disease. Emerging evidence shows that vitamin D helps the immune system to fight infection and to control inflammation and could potentially help prevent respiratory complications in patients with sickle cell disease. The investigators hypothesize that oral vitamin D3, 100,000 IU (2.5 mg), given once a month to a group of children and adolescents with sickle cell disease, will reduce the rate of respiratory events (infection, asthma exacerbation and acute chest syndrome) compared to the rate in a group given standard dose oral vitamin D3, 12,000 IU (0.3 mg) given once a month. Funding Source - U.S. Food & Drug Administration, Office of Orphan Products Development

Detailed Description
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This study will be a Phase 2 double-blind randomized clinical trial in 80 patients with sickle cell disease, ages 3 to 20 years-old, comparing a 2-year monthly oral dose of vitamin D3, 100,000 IU (equivalent to 3,300 IU/day) to a standard monthly dose, 12,000 IU (400 IU/day) in reducing the rate of respiratory events (defined as respiratory infections, acute asthma exacerbation, and the acute chest syndrome) in children and adolescents with sickle cell disease in comparison with the rates of respiratory events over a baseline period of one year. Eligible participants (130 patients) will initially be screened to determine their blood vitamin D levels (serum 25-hydroxyvitamin D). Those with 25-hydroxyvitamin D levels between 5 and 60 ng/mL will be eligible for randomization. At study entry, blood and urine samples will be collected for routine and special blood tests including tests on immune function, inflammation, and bone function. Children above 5 years old will also have lung function and muscle strength tests. Participants will be followed once a month to administer the study medication (oral vitamin D3) and to monitor any side effects from the study medication by history, examination and blood and urine tests. After 12 and 24 months of therapy, the same study procedures at study entry will be repeated. This study could help establish oral vitamin D3 as a simple, low cost treatment to reduce respiratory complications in children and adolescents with sickle cell disease.

Official Title
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Vitamin D for Sickle-cell Respiratory Complications

Conditions
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Sickle Cell Disease, Vitamin D Deficiency, Acute Chest Syndrome, Asthma, Respiratory Infections

Intervention / Treatment
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* Drug: Experimental: Vitamin D3 100,000 IU
* Drug: Active Comparator: Vitamin D3 12,000 IU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of sickle cell disease (HbSS, HbSC, HbS Beta-thalassemia) Age 3 to 20 years old Exclusion Criteria: Patient (or parent or guardian) 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 other therapeutic 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 Patients on chronic red blood cell transfusion therapy Absence of baseline record of respiratory events (respiratory infections, asthma exacerbations, episodes of acute chest syndrome) for the preceding year Pregnancy

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3 100,000 IU<br>Oral vitamin D3, 100,000 IU [2.5 mg] given once a month | Drug: Experimental: Vitamin D3 100,000 IU<br>* Oral vitamin D3, 100,000 IU [2.5 mg] given once a month<br>* Other names: Cholecalciferol;|
| Active Comparator: Vitamin D3 12,000 IU<br>Standard dose oral vitamin D3 12,000 IU [0.3 mg] given once a month | Drug: Active Comparator: Vitamin D3 12,000 IU<br>* Standard dose oral vitamin D3 12,000 IU [0.3 mg] given once a month<br>* Other names: Cholecalciferol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Respiratory events | Defined as respiratory infection, acute asthma exacerbation, and acute chest syndrome | Every year for 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function tests | Standard pulmonary function tests | Every year for 2 years | 
| Immune function | Serum cytokines to measure T-cell effector and regulatory function Measures of systemic inflammation [high-sensitivity C-reactive protein (hs-CRP), Whole Blood Count (WBC), platelets) | Every 6 months for 2 years | 
| Bone function and bone turnover markers | Intact parathyroid hormone Serum C-terminal telopeptides of Type I collagen (CTX) Aminoterminal propeptide of Type 1 procollagen (P1NP) | Every 6 months for 2 years | 
| Muscle strength | Hand grip | Every year for 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease, acute chest syndrome, respiratory complications, vitamin D