Daily Vitamin D for Sickle-cell Respiratory Complications

NCT ID: NCT04170348

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-15
• Study Completion Date: 2024-06-18

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Daily oral vitamin D3

Oral vitamin D3, 3,333 IU

Group Type: EXPERIMENTAL

Daily oral vitamin D3, 3,333 IU

Intervention Type: DRUG

Oral vitamin D3, 3,333 IU, will be administered daily.

Monthly bolus oral vitamin D3

Bolus oral vitamin D3, 100,000 IU

Group Type: ACTIVE_COMPARATOR

Monthly oral vitamin D3, 100,000 IU

Intervention Type: DRUG

Oral vitamin D3, 100,000 IU, will be administered monthly.

Placebo oral tablet

Intervention Type: DRUG

Participants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month.

Interventions

Daily oral vitamin D3, 3,333 IU

Oral vitamin D3, 3,333 IU, will be administered daily.

Intervention Type: DRUG

Monthly oral vitamin D3, 100,000 IU

Oral vitamin D3, 100,000 IU, will be administered monthly.

Intervention Type: DRUG

Placebo oral tablet

Participants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month.

Intervention Type: DRUG

Other Intervention Names

Cholecalciferol for oral administration; Cholecalciferol for oral administration

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FDA Office of Orphan Products Development

FED

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Margaret T. Lee

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gary M Brittenham, MD

Role: STUDY_CHAIR

Columbia University

Margaret T Lee, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Columbia University Medical Center

New York, New York, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 29712666 (View on PubMed)

Williams KM, Lee MT, Licursi M, Brittenham GM, Fennoy I. Response to Long-term Vitamin D Therapy for Bone Disease in Children With Sickle Cell Disease. J Pediatr Hematol Oncol. 2018 Aug;40(6):458-461. doi: 10.1097/MPH.0000000000001155.

Reference Type: BACKGROUND

PMID: 29668535 (View on PubMed)

De A, Anekwe CV, Kattan M, Yao Y, Jin Z, Brittenham GM, Lee MT. Validation of a Questionnaire to Identify Respiratory Tract Infections in Children With Sickle Cell Disease. J Pediatr Hematol Oncol. 2021 Jul 1;43(5):e661-e665. doi: 10.1097/MPH.0000000000002164.

Reference Type: BACKGROUND

PMID: 33885042 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R01FD006372

Identifier Type: FDA

Identifier Source: secondary_id

View Link

AAAS0396

Identifier Type: -

Identifier Source: org_study_id