Vitamin D for Sickle-cell Respiratory Complications

Sponsor

Gary M Brittenham, MD (Other)

Overall Status

Completed

CT.gov ID

NCT01443728

Collaborator

(none)

130

Enrollment

Location

Arms

38.1

Actual Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease Vitamin D Deficiency Acute Chest Syndrome Asthma Respiratory Infections	Drug: Experimental: Vitamin D3 100,000 IU Drug: Active Comparator: Vitamin D3 12,000 IU	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Vitamin D for Sickle-cell Respiratory Complications

Actual Study Start Date :

Dec 13, 2011

Actual Primary Completion Date :

Jun 20, 2013

Actual Study Completion Date :

Feb 15, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vitamin D3 100,000 IU Oral vitamin D3, 100,000 IU [2.5 mg] given once a month	Drug: Experimental: Vitamin D3 100,000 IU Oral vitamin D3, 100,000 IU [2.5 mg] given once a month Other Names: Cholecalciferol
Active Comparator: Vitamin D3 12,000 IU Standard dose oral vitamin D3 12,000 IU [0.3 mg] given once a month	Drug: Active Comparator: Vitamin D3 12,000 IU Standard dose oral vitamin D3 12,000 IU [0.3 mg] given once a month Other Names: Cholecalciferol

Arm

Intervention/Treatment

Experimental: Vitamin D3 100,000 IU

Oral vitamin D3, 100,000 IU [2.5 mg] given once a month

Drug: Experimental: Vitamin D3 100,000 IU

Oral vitamin D3, 100,000 IU [2.5 mg] given once a month

Other Names:

Cholecalciferol

Active Comparator: Vitamin D3 12,000 IU

Standard dose oral vitamin D3 12,000 IU [0.3 mg] given once a month

Drug: Active Comparator: Vitamin D3 12,000 IU

Standard dose oral vitamin D3 12,000 IU [0.3 mg] given once a month

Other Names:

Cholecalciferol

Outcome Measures

Primary Outcome Measures

Respiratory events [Every year for 2 years]
Defined as respiratory infection, acute asthma exacerbation, and acute chest syndrome

Secondary Outcome Measures

Pulmonary function tests [Every year for 2 years]
Standard pulmonary function tests
Immune function [Every 6 months for 2 years]
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)
Bone function and bone turnover markers [Every 6 months for 2 years]
Intact parathyroid hormone Serum C-terminal telopeptides of Type I collagen (CTX) Aminoterminal propeptide of Type 1 procollagen (P1NP)
Muscle strength [Every year for 2 years]
Hand grip

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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