Clinical trial NCT04170348: Daily Vitamin D for Sickle-cell Respiratory Complications
Official title: Daily Vitamin D for Sickle-cell Respiratory Complications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Columbia University
Sponsor class: OTHER
First posted: 2019-11-20
Enrollment: 69
Sex: ALL
Minimum age (years): 3
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Controlled, double-masked, randomized Phase 2 clinical trial
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Rate of Respiratory Events
timeFrame: Screening up to month 24
Secondary outcomes:
measure: Change in Forced Vital Capacity (FVC)
timeFrame: Baseline and month 24
measure: Change in Forced Expiratory Volume in 1 second (FEV1)
timeFrame: Baseline and month 24
measure: Change in Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity ratio
timeFrame: Baseline and month 24
measure: Change in Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75)
timeFrame: Baseline and month 24
measure: Change in ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)
timeFrame: Baseline and month 24
measure: Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
timeFrame: Baseline and month 24
measure: Change in blood hemoglobin concentration (Hb)
timeFrame: Baseline up to month 24
measure: Change in blood platelet concentration
timeFrame: Baseline up to month 24
measure: Change in serum C-reactive protein (CRP)
timeFrame: Baseline up to month 24
Other outcomes:
measure: Change in Fractional Concentration of Exhaled Nitric Oxide (FENO)
timeFrame: Baseline and month 24
measure: Change in Maximum Inspiratory Pressure (MIP)
timeFrame: Baseline and month 24
measure: Change in Maximum Expiratory Pressure (MEP)
timeFrame: Baseline and month 24
measure: Change in interleukin 2 (IL 2) concentration
timeFrame: Baseline up to month 24
measure: Change in interleukin 4 (IL 4) concentration
timeFrame: Baseline up to month 24
measure: Change in interleukin 5 (IL 5) concentration
timeFrame: Baseline up to month 24
measure: Change in interleukin 13 (IL 13) concentration
timeFrame: Baseline up to month 24
measure: Change in interferon gamma (IFN gamma). concentration
timeFrame: Baseline up to month 24
measure: Change in interleukin 10 (IL 10) concentration
timeFrame: Baseline up to month 24
measure: Change in Transforming Growth Factor beta (TGF beta)
timeFrame: Baseline up to month 24
measure: Change in interleukin 1alpha (IL 1alpha) concentration
timeFrame: Baseline up to month 24
measure: Change in interleukin 1beta (IL 1beta) concentration
timeFrame: Baseline up to month 24
measure: Change in Tumor Necrosis Factor alpha (TNF alpha) concentration
timeFrame: Baseline up to month 24
measure: Change in C-terminal telopeptides of Type I collagen (CTX)
timeFrame: Baseline up to month 24
measure: Change in intact N-terminal propeptide of type I procollagen (P1NP)
timeFrame: Baseline up to month 24
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Gary M Brittenham, MD
role: STUDY_CHAIR
affiliation: Columbia University
name: Margaret T Lee, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.