Daily Vitamin D for Sickle-cell Respiratory Complications

Columbia University58 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Eligibility

Sex: ALLMin age: 3 YearsMax age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Diagnosis of sickle cell disease (Hb SS, Hb SC, Hb S-Beta-thalassemia) 2. Age 3-20 years old Exclusion Criteria: 1. Patient unwilling or unable to provide written informed consent (and assent, if applicable) 2. Patient unable or unwilling to comply with requirements of the clinical trial 3. Participation in another clinical trial 4. Current diagnosis of rickets 5. History of hypercalcemia or diagnosis of any medical condition associated with hypercalcemia, including primary hyperparathyroidism, malignancy, sarcoidosis, tuberculosis, granulomatous disease, familial hypocalciuric hypercalcemia 6. Current use of corticosteroids, excluding inhaled steroids 7. Current use of anticonvulsants (phenytoin, phenobarbital, carbamazepine) 8. Therapy with thiazide diuretics or lithium carbonate 9. Known liver or renal disease 10. 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 11. Patients on chronic red blood cell transfusion therapy

Outcomes

Primary Outcomes

Annual Rate of Respiratory Events

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.

Time frame: Month 12, Month 24

Secondary Outcomes

Mean Forced Vital Capacity (FVC % Predicted)

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.