Study of Vitamin D in Children With Sickle Cell Disease

Sponsor

Gary M Brittenham, MD (Other)

Overall Status

Completed

CT.gov ID

NCT01276587

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This pilot study aims to answer the question whether monthly oral vitamin D3 supplementation, 100,000 IU, will be safe and effective in raising serum 25-hydroxyvitamin D (form of vitamin D measured in the blood) to levels considered sufficient (30 ng/mL) but well below the threshold for toxicity (150 ng/mL) in children with sickle cell disease. Information from this study will be crucial before we perform a larger clinical trial to determine the effects of vitamin D in reducing respiratory complications in patients with sickle cell disease.

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Vitamin D3	Phase 1/Phase 2

Detailed Description

Sickle cell disease is a genetic red blood cell disorder that affects an estimated 89,000 Americans, predominantly those of African ancestry. The leading causes of morbidity and of death in sickle cell disease are respiratory complications, particularly a life-threatening lung disease unique to sickle cell disease called the "acute chest syndrome". An infectious trigger and a pro-inflammatory state appear to be critical mechanisms of the respiratory problems in sickling disorders. Emerging evidence that vitamin D has antimicrobial and anti-inflammatory functions in the respiratory tract, and the recognition of widespread vitamin D insufficiency in sickle cell children provide a compelling new rationale for vitamin D supplementation in sickle cell disease.

This will be an open label, single arm study to assess the efficacy and safety of oral vitamin D3 100,000 IU administered monthly for six months in children and adolescents with sickle cell disease. Twelve pediatric patients with sickle cell disease, 3-20 years old, will be recruited. The primary outcome measure (efficacy and safety) will be serum 25-hydroxyvitamin D concentration. Other safety measures will include serum calcium and urinary calcium and creatinine. Serial measurements of serum 25-hydroxyvitamin D, serum chemistries, and urinary calcium and creatinine will be performed at baseline entry, monthly for six months during treatment with vitamin D3, and at study exit. Other measures relevant to our planned Phase 2 clinical trial, including markers of bone turnover, immune function, and inflammation, will also be obtained at baseline, midpoint and exit. Recruitment and enrollment of subjects is expected to be for 3 months; study assessments will be for 7 months (1 month screening and 6 months treatment); and, the remaining 2 months will be devoted to data collation and analysis.

Study Procedures

Screening: After signing written informed consent by a parent or legal guardian (and assent, if applicable) or patient, eligible participants will undergo a screening examination including a standardized history and physical examination.

A venous blood sample will be obtained for baseline screening measures including serum 25-hydroxyvitamin D, serum chemistries, and urine calcium and creatinine. Within one month, eligible participants who do not have any of the exclusion criteria will return for enrollment in the pilot study.

Intervention: Participants will be seen monthly for administration of oral vitamin D3 100,000 IU under the direct observation by the Clinical Research Nurse. History and examination will be performed to capture symptoms and signs of adverse events. Questionnaires to collect data on vitamin D and calcium dietary intake and respiratory events will be administered. Venous blood and urine samples for study assessments (serum 25-hydroxyvitamin D, serum albumin, calcium and phosphate, urine calcium and creatinine) will be obtained at each visit prior to administration of study drug.

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Vitamin D Therapy to Prevent Respiratory Complications in Children With Sickle Cell Disease

Study Start Date :

Jan 1, 2011

Actual Primary Completion Date :

Jun 1, 2011

Actual Study Completion Date :

Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm	Drug: Vitamin D3 Oral vitamin D3 100,000 IU administered monthly for six months in children and adolescents with sickle cell disease Other Names: Vitamin D

Arm

Intervention/Treatment

Experimental: Single arm

Drug: Vitamin D3

Oral vitamin D3 100,000 IU administered monthly for six months in children and adolescents with sickle cell disease

Other Names:

Vitamin D

Outcome Measures

Primary Outcome Measures

Serum 25-hydroxyvitamin D concentration [seven months]
Serial measurements of serum 25-hydroxyvitamin D, serum chemistries, and urinary calcium and creatinine, markers of bone turnover, immune function, and inflammation will be performed at baseline entry, monthly for six months during treatment with vitamin D3, and at study exit.

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

patients with sickle cell disease
3 to 20 years old
pregnant females with sickle cell disease are eligible

Exclusion Criteria:

no informed consent or assent
unable or unwilling to comply with requirements of the clinical trial
participation in another clinical trial
history of hypercalcemia or diagnosis of any medical condition associated with hypercalcemia, such as primary hyperparathyroidism, malignancy, familial hypocalciuric hypercalcemia, William's syndrome and other rare causes
therapy with thiazide diuretics or lithium carbonate
known renal or liver disease
known malabsorption syndrome and inflammatory bowel disease
chronic use of corticosteroids, excluding inhaled steroids
current use of anticonvulsants (phenytoin, phenobarbital, carbamazepine)
current intake of vitamin D and calcium supplements
initiation of hydroxyurea or iron chelation therapy within the past 3 months
serum 25hydroxyvitamin D >60 ng/mL