Study of Vitamin D in Children With Sickle Cell Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: Vitamin D3

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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 20 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum 25-hydroxyvitamin D Concentration	Serum 25-hydroxyvitamin D level was measured at 6 months.	Up to 6 months

Collaborators and Investigators

• Sponsor: Gary M Brittenham, MD
• Investigators: Principal Investigator: Margaret T Lee, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: January 12, 2011
• First Submitted That Met QC Criteria: January 12, 2011
• First Posted (Estimate): January 13, 2011

Study Record Updates

• Last Update Posted (Actual): April 12, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: safety; children; vitamin D; sickle cell disease
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: AAAF2598