Daily Vitamin D for Sickle-cell Respiratory Complications

NCT04170348 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: AAAS0396R01FD006372
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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).

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

Keywords

Sickle Cell Disease; Acute Chest Syndrome; Respiratory Complication; Vitamin D Deficiency

Outcome Measures

Primary Outcomes (1)

• 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.

  Month 12, Month 24

Secondary Outcomes (9)

• Mean Forced Vital Capacity (FVC % Predicted)

  Baseline, Month 24

• Forced Expiratory Volume in 1 Second (FEV1)

  Baseline, Month 24

• Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity Ratio

  Baseline, Month 24

• Forced Expiratory Flow at 25%-75% Vital Capacity (FEF25-75, % Predicted)

  Baseline, Month 24

• Ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)

  Baseline, Month 24

Study Arms (2)

Daily oral vitamin D3

EXPERIMENTAL

Oral vitamin D3, 3,333 IU

Drug: Daily oral vitamin D3, 3,333 IU

Monthly bolus oral vitamin D3

ACTIVE COMPARATOR

Bolus oral vitamin D3, 100,000 IU

Drug: Monthly oral vitamin D3, 100,000 IU; Drug: Placebo oral tablet

Interventions

Daily oral vitamin D3, 3,333 IU DRUG

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

Also known as: Cholecalciferol for oral administration

Daily oral vitamin D3

Monthly oral vitamin D3, 100,000 IU DRUG

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

Also known as: Cholecalciferol for oral administration

Monthly bolus oral vitamin D3

Placebo oral tablet DRUG

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

Monthly bolus oral vitamin D3

Eligibility Criteria

• Age: 3 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead
• FDA Office of Orphan Products Development: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (3)

• 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.

  PMID: 29712666 BACKGROUND

• 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.

  PMID: 29668535 BACKGROUND

• 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.

  PMID: 33885042 BACKGROUND

MeSH Terms

Conditions

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

Interventions

Cholecalciferol; Administration, Oral

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Infections; Nutritional and Metabolic Diseases; Deficiency Diseases; Malnutrition

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids; Drug Administration Routes; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Margaret T. Lee, Professor of Pediatric
• Organization: CUIMC

ml653@cumc.columbia.edu

212-305-6290

Study Officials

• Gary M Brittenham, MD

  Columbia University

  STUDY CHAIR

• Margaret T Lee, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking will be performed by the Research Pharmacy; all other research staff and participants will be blinded to allocation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: Controlled, double-masked, randomized Phase 2 clinical trial

Study Record Dates

• First Submitted: October 1, 2019
• First Posted: November 20, 2019
• Study Start: September 15, 2020
• Primary Completion: June 18, 2024
• Study Completion: June 18, 2024
• Last Updated: September 24, 2025
• Results First Posted: September 24, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)