Vitamin D for Sickle-cell Respiratory Complications

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

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; Asthma; Sickle Cell Disease; Acute Chest Syndrome; Respiratory Infections
• Intervention / Treatment: Drug: Experimental: Vitamin D3 100,000 IU; Drug: Active Comparator: Vitamin D3 12,000 IU

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 Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Phase 2

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
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory events	Defined as respiratory infection, acute asthma exacerbation, and acute chest syndrome	Every year for 2 years

Secondary Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Lee MT, Kattan M, Fennoy I, Arpadi SM, Miller RL, Cremers S, McMahon DJ, Nieves JW, Brittenham GM. Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease. Blood Adv. 2018 May 8;2(9):969-978. doi: 10.1182/bloodadvances.2017013979.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2011
• Primary Completion (Actual): June 20, 2013
• Study Completion (Actual): February 15, 2015

Study Registration Dates

• First Submitted: September 27, 2011
• First Submitted That Met QC Criteria: September 28, 2011
• First Posted (Estimate): September 30, 2011

Study Record Updates

• Last Update Posted (Actual): July 27, 2020
• Last Update Submitted That Met QC Criteria: July 23, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: vitamin D; sickle cell disease; respiratory complications; acute chest syndrome
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Hematologic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Anemia; Avitaminosis; Deficiency Diseases; Malnutrition; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Vitamin D Deficiency; Anemia, Sickle Cell; Respiratory Tract Infections; Acute Chest Syndrome; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: AAAE3244; R01FD003894 (U.S. FDA Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No