Vitamin D for Sickle-cell Respiratory Complications

Phase 2

Completed

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

Registration Number: NCT01443728

Lead Sponsor: Gary M Brittenham, MD

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 70

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Mean Annual Rate of Respiratory Events	Up to 2 years	Defined as respiratory infection, acute asthma exacerbation, and acute chest syndrome.

Secondary Outcome Measures

Name	Time	Method
FeNO	Up to 2 years	Fractional exhaled nitric oxide (FeNO) will be measured in parts per billion (ppb).
Forced Vital Capacity (FVC)	Up to 2 years	Percent predicted forced vital capacity will be calculated for both groups.
FEV1/FVC Ratio	Up to 2 years	The ratio of FEV1 to FVC will be calculated (in percentage).
DLCO	Up to 2 years	Percent predicted of the diffusing capacity for carbon monoxide in the lungs (DLCO) will be measured.
Mean 25-Hydroxyvitamin D (25-OHD)	2 years	The overall mean serum 25-OHD concentration will be measured for both groups.
FEF 25-75	Up to 2 years	Percent predicted forced expiratory flow (FEF) during expiration of 25 to 75% of the FVC will be calculated.
Forced Expiratory Volume (FEV) in 1 Second (FEV1)	Up to 2 years	Percent predicted forced expiratory volume in 1 second will be calculated for both groups.
RV/TLC Ratio	Up to 2 years	The ratio of residual volume (RV) to total lung capacity (TLC) will be calculated (in percentage).
MIP	Up to 2 years	Maximum inspiratory pressure (MIP) will be measured.
Hand-grip, Right	Up to 2 years	Muscle strength was measured by looking at hand-grip strength in the right hand.
MEP	Up to 2 years	Maximum expiratory pressure (MEP) will be measured.
Hand-grip, Left	Up to 2 years	Muscle strength was measured by looking at hand-grip strength in the left hand.
Hand-grip, Dominant	Up to 2 years	Muscle strength was measured by looking at hand-grip strength in the dominant hand.