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: Bolus 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.

Study Timeline

• Study First Submitted: 2019-10-01
• Study First Submitted QC: 2019-11-18
• Study First Posted: 2019-11-20
• Study Start: 2020-09-15
• Primary Completion: 2024-06-18
• Study Completion: 2024-06-18
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-12
• Last Update Posted: 2025-03-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

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

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	Placebo oral tablet	Bolus oral vitamin D3, 100,000 IU
Monthly bolus oral vitamin D3	Bolus oral vitamin D3, 100,000 IU	Bolus oral vitamin D3, 100,000 IU

Primary Outcome Measures

Name	Time	Method
Rate of Respiratory Events	Screening up to month 24	Annual rate of 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
Change in Forced Vital Capacity (FVC)	Baseline and month 24	Change forced vital capacity (FVC; % predicted) from baseline
Change in Forced Expiratory Volume in 1 second (FEV1)	Baseline and month 24	Change in Forced Expiratory Volume in 1 second (FEV1; % predicted) from baseline.
Change in Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity ratio	Baseline and month 24	Change in Forced Expiratory Volume in 1 second (FEV1; % predicted)/Forced Vital Capacity (FVC) \[FEV1/FVC\] % predicted from baseline.
Change in Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75)	Baseline and month 24	Change in Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75) % predicted from baseline.
Change in ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)	Baseline and month 24	Change in per cent of the ratio of Residual Lung Volume (RV) to Total Lung Capacity (RV/TLC) from baseline.
Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)	Baseline and month 24	Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO; % predicted) from baseline
Change in blood hemoglobin concentration (Hb)	Baseline up to month 24	Change in blood hemoglobin concentration (Hb; g/dL) from baseline
Change in blood platelet concentration	Baseline up to month 24	Change in blood platelet concentration (platelets/mL) from baseline
Change in serum C-reactive protein (CRP)	Baseline up to month 24	Change in serum C-reactive protein (CRP; mg/L) from baseline

Trial Locations

Locations (1)

Columbia University Medical Center; 🇺🇸 New York, New York, United States