Daily Vitamin D for Sickle-cell Respiratory Complications

Phase 2

Completed

Conditions: Anemia, Sickle Cell
Acute Chest Syndrome
Respiratory Tract Infections
Vitamin D Deficiency
Respiratory Tract Diseases
Respiration Disorders
Lung Diseases
Nutrition Disorders
Anemia, Hemolytic, Congenital
Asthma

Interventions: Drug: Daily oral vitamin D3, 3,333 IU
Drug: Monthly oral vitamin D3, 100,000 IU
Drug: Placebo oral tablet

Registration Number: NCT04170348

Lead Sponsor: Columbia University

Brief Summary: This study aims to answer the question whether daily oral vitamin D supplementation can reduce the risk of respiratory or lung complications in children and adolescents with sickle cell disease. Respiratory problems are the leading causes of sickness and of death in sickle cell disease. The investigators hypothesize that daily oral vitamin D3, compared to monthly oral vitamin D, will rapidly increase circulating vitamin D3, and reduce the rate of respiratory complications by 50% or more within the first year of supplementation in children and adolescents with sickle cell disease.

This study is funded by the FDA Office of Orphan Products Development (OOPD).

Detailed Description: This is a 2-year controlled, double-blind, randomized Phase 2 clinical trial comparing the efficacy in reducing the rate of respiratory events in sickle-cell disease of daily oral vitamin D3 (3,333 IU/d) with monthly bolus oral vitamin D3, (100,000 IU/mo) as a control. The scientific premise of the clinical trial is that circulating concentrations of vitamin D3, the parent compound, are the principal determinant of the anti-infective and immunomodulatory effects of supplementation.

Eligible participants will be initially screened to determine their blood vitamin D levels. Those with 25-hydroxyvitamin D levels between 5 and 60 ng/mL will be assigned by chance to one of the two arms for 24 months. Participants will be checked every month and will have periodic blood and urine tests to monitor for any side effects of the study treatments. Children above 5 y/o who can cooperate and understand the procedure will have lung function test at baseline and at 24 months. Showing that a monthly dose of vitamin D reduces lung infections, asthma and the acute chest syndrome could help establish this simple, low-cost treatment as a way to decrease sickness and deaths in children and adolescents with sickle-cell disease.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 58

Inclusion Criteria

Diagnosis of sickle cell disease (Hb SS, Hb SC, Hb S-Beta-thalassemia)
Age 3-20 years old

Exclusion Criteria

Patient 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 another 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Daily oral vitamin D3	Daily oral vitamin D3, 3,333 IU	Oral vitamin D3, 3,333 IU
Monthly bolus oral vitamin D3	Monthly oral vitamin D3, 100,000 IU	Bolus oral vitamin D3, 100,000 IU
Monthly bolus oral vitamin D3	Placebo oral tablet	Bolus oral vitamin D3, 100,000 IU

Primary Outcome Measures

Name	Time	Method
Annual Rate of Respiratory Events	Month 12, Month 24	Respiratory events will be calculated as the sum of respiratory infection, asthma exacerbation, and acute chest syndrome, as ascertained by use of a validated questionnaire.

Secondary Outcome Measures

Name	Time	Method
Mean Forced Vital Capacity (FVC % Predicted)	Baseline, Month 24	This is to measure the forced vital capacity (FVC; % predicted) at baseline and at month 24. Forced Vital Capacity (FVC) is a key measure of lung function that indicates the total volume of air a person can forcefully exhale after taking a deep breath. It is calculated using spirometry, which assesses lung capacity and helps diagnose respiratory conditions. Predicted FVC: The FVC is compared to predicted values based on age, height, and sex to determine if it is within the normal range (80% or more of predicted). Interpretation: A low FVC may indicate obstruction (e.g., asthma or COPD), while a high FVC may suggest restriction in lung function. Baseline Measurement: It is essential to establish a baseline FVC to monitor changes over time and assess the effectiveness of treatments. For accurate interpretation, it is crucial to compare FVC results with other measurements, such as FEV1, to identify the presence of obstructive or restrictive lung disease.
Forced Expiratory Volume in 1 Second (FEV1)	Baseline, Month 24	Forced Expiratory Volume in 1 second (FEV1; % predicted) at baseline and at month 24.
Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity Ratio	Baseline, Month 24	Forced Expiratory Volume in 1 second (FEV1; % predicted)/Forced Vital Capacity (FVC) \[FEV1/FVC\] % predicted at baseline and month 24
Forced Expiratory Flow at 25%-75% Vital Capacity (FEF25-75, % Predicted)	Baseline, Month 24	Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75) % predicted at baseline and month 24 .
Ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)	Baseline, Month 24	Ratio of Residual Lung Volume (RV) to Total Lung Capacity (RV/TLC) at baseline and month 24.
Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)	Baseline, Month 24	Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO; % predicted) at baseline and month 24
Neutrophil Count	Baseline, Month 12, Month 24	Blood Neutrophil Count in percentage at baseline, month 12 and month 24
Platelet Count	Baseline, Month 12, Month 24	Blood Platelet Count (Platelets\*10\^3/ per μL) at baseline, month 12 and month 24
Serum C-reactive Protein (CRP)	Baseline, Month 12, Month 24	Serum C-reactive protein (CRP; mg/L) at baseline, month 12 and month 24

Trial Locations

Locations (1): Columbia University Medical Center
🇺🇸
New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States