Vitamin D for Sickle-cell Respiratory Complications

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gary M Brittenham, MD, Columbia University
ClinicalTrials.gov Identifier:
NCT01443728
First received: September 27, 2011
Last updated: May 14, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Sickle Cell Disease
Vitamin D Deficiency
Acute Chest Syndrome
Asthma
Respiratory Infections
Drug: Vitamin D3
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Vitamin D for Sickle-cell Respiratory Complications

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Respiratory events (defined as respiratory infection, acute asthma exacerbation, and acute chest syndrome) [ Time Frame: Every year for 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pulmonary function tests [ Time Frame: Every year for 2 years ] [ Designated as safety issue: No ]
  • Immune function [ Time Frame: Every 6 months for 2 years ] [ Designated as safety issue: No ]
    Serum cytokines to measure T-cell effector and regulatory function Measures of systemic inflammation (hs-CRP, WBC, platelets)

  • Bone function and bone turnover markers [ Time Frame: Every 6 months for 2 years ] [ Designated as safety issue: No ]
    Intact parathyroid hormone Serum C-terminal telopeptides of Type I collagen (CTX) Aminoterminal propeptide of Type 1 procollagen (P1NP)

  • Muscle strength (Hand grip) [ Time Frame: Every year for 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 130
Study Start Date: December 2011
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vitamin D3 100,000 IU
Oral vitamin D3, 100,000 IU [2.5 mg] given once a month
Drug: Vitamin D3
Vitamin D3 100,000 IU orally once a month
Other Name: Cholecalciferol
Active Comparator: Vitamin D3 12,000 IU
Standard dose oral vitamin D3 12,000 IU [0.3 mg] given once a month
Drug: Vitamin D3
Vitamin D3 12,000 IU orally once a month
Other Name: Cholecalciferol

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.

  Eligibility

Ages Eligible for Study:   3 Years to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of sickle cell disease (HbSS, SC, S 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01443728

Locations
United States, New York
Columbia University Medical Center
New york, New York, United States, 10032
Sponsors and Collaborators
Gary M Brittenham, MD
Investigators
Principal Investigator: Gary Brittenham, MD Columbia University
Principal Investigator: Margaret T Lee, MD Columbia University
  More Information

No publications provided

Responsible Party: Gary M Brittenham, MD, James A. Wolff Professor of Pediatrics, Columbia University
ClinicalTrials.gov Identifier: NCT01443728     History of Changes
Other Study ID Numbers: AAAE3244, R01FD003894
Study First Received: September 27, 2011
Last Updated: May 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Columbia University:
sickle cell disease
acute chest syndrome
respiratory complications
vitamin D

Additional relevant MeSH terms:
Anemia, Sickle Cell
Asthma
Respiratory Tract Infections
Vitamin D Deficiency
Acute Chest Syndrome
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Infection
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Respiration Disorders
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on August 19, 2014