ViDAS-2: Daily Vitamin D for Sickle-cell Respiratory Complications

• Sponsor: Gary M Brittenham, MD (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04170348
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 53.5
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Daily oral vitamin D3, 3,333 IU; Drug: Bolus oral vitamin D3, 100,000 IU; Drug: Placebo oral tablet	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Controlled, double-masked, randomized Phase 2 clinical trialControlled, double-masked, randomized Phase 2 clinical trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Masking will be performed by the Research Pharmacy; all other research staff and participants will be blinded to allocation.
• Primary Purpose: Prevention
• Official Title: Daily Vitamin D for Sickle-cell Respiratory Complications
• Actual Study Start Date: Sep 15, 2020
• Anticipated Primary Completion Date: Jun 30, 2024
• Anticipated Study Completion Date: Feb 28, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daily oral vitamin D3 Oral vitamin D3, 3,333 IU	Drug: Daily oral vitamin D3, 3,333 IU; Oral vitamin D3, 3,333 IU, will be administered daily.; Other Names: Cholecalciferol for oral administration 10-secocholeta-5,7,10(19)-trien-3B-ol for oral administration
Active Comparator: Monthly bolus oral vitamin D3 Bolus oral vitamin D3, 100,000 IU	Drug: Bolus oral vitamin D3, 100,000 IU; Bolus oral vitamin D3, 100,000 IU, will be administered monthly.; Other Names: Cholecalciferol for oral administration 10-secocholeta-5,7,10(19)-trien-3B-ol for oral administration ; 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.

Outcome Measures

Primary Outcome Measures

1. 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

1. Change in Forced Vital Capacity (FVC) [Baseline and month 24]

   Change forced vital capacity (FVC; % predicted) from baseline

2. 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.

3. 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.

4. 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.

5. 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.

6. 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

7. Change in Fractional Concentration of Exhaled Nitric Oxide (FENO) [Baseline and month 24]

   Change in Fractional Concentration of Exhaled Nitric Oxide (FENO) in parts per billion (ppb) from baseline

8. Change in Maximum Inspiratory Pressure (MIP) [Baseline and month 24]

   Change in Maximum Inspiratory Pressure (MIP; cm H2O) from baseline

9. Change in Maximum Expiratory Pressure (MEP) [Baseline and month 24]

   Change in Maximum Expiratory Pressure (MEP; cm H2O) from baseline

10. Change in interleukin 2 (IL 2) concentration [Baseline up to month 24]

    Change in serum interleukin 2 concentration (IL 2; pg/mL ) from baseline

11. Change in interleukin 4 (IL 4) concentration [Baseline up to month 24]

    Change in serum interleukin 4 concentration (IL 4; pg/mL ) from baseline

12. Change in interleukin 5 (IL 5) concentration [Baseline up to month 24]

    Change in serum interleukin 5 concentration (IL 5; pg/mL ) from baseline

13. Change in interleukin 13 (IL 13) concentration [Baseline up to month 24]

    Change in serum interleukin 13 concentration (IL 13; pg/mL ) from baseline

14. Change in interferon gamma (IFN gamma). concentration [Baseline up to month 24]

    Change in serum interferon gamma concentration (IFN gamma; pg/mL ) from baseline

15. Change in interleukin 10 (IL 10) concentration [Baseline up to month 24]

    Change in serum interleukin 10 concentration (Iinterleukin 10; pg/mL ) from baseline

16. Change in Transforming Growth Factor beta (TGF beta) [Baseline up to month 24]

    Change in serum Transforming Growth Factor beta (TGF beta; pg/mL ) from baseline

17. Change in blood hemoglobin concentration (Hb) [Baseline up to month 24]

    Change in blood hemoglobin concentration (Hb; g/dL) from baseline

18. Change in blood platelet concentration [Baseline up to month 24]

    Change in blood platelet concentration (platelets/mL) from baseline

19. Change in serum C-reactive protein (CRP) [Baseline up to month 24]

    Change in serum C-reactive protein (CRP; mg/L) from baseline

20. Change in interleukin 1alpha (IL 1alpha) concentration [Baseline up to month 24]

    Change in serum interleukin 1alpha (IL 1alpha; pg/mL) from baseline

21. Change in interleukin 1beta (IL 1beta) concentration [Baseline up to month 24]

    Change in serum interleukin 1beta (IL 1beta; pg/mL) from baseline

22. Change in Tumor Necrosis Factor alpha (TNF alpha) concentration [Baseline up to month 24]

    Change in serum Tumor Necrosis Factor alpha (TNF alpha; pg/mL) from baseline

23. Change in C-terminal telopeptides of Type I collagen (CTX) [Baseline up to month 24]

    Change in serum C-terminal telopeptides of Type I collagen (CTX; ng/mL) from baseline

24. Change in intact N-terminal propeptide of type I procollagen (P1NP) [Baseline up to month 24]

    Chang in serum intact N-terminal propeptide of type I procollagen (P1NP; µg/L) from baseline.=

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 20 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Columbia University Medical Center	New York	New York	United States	10032

Sponsors and Collaborators

• Gary M Brittenham, MD

Investigators

• Principal Investigator: Gary M Brittenham, MD, Columbia University
• Principal Investigator: Margaret T Lee, MD, Columbia University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Response to Long-term Vitamin D Therapy for Bone Disease in Children With Sickle Cell Disease.
• Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease

Publications

• 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.
• 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.
• 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.

• Responsible Party: Gary M Brittenham, MD, James A. Wolff Professor of Pediatrics and Professor of Medicine, Columbia University
• ClinicalTrials.gov Identifier: NCT04170348
• Other Study ID Numbers: AAAS0396; R01FD006372
• First Posted: Nov 20, 2019
• Last Update Posted: Jun 27, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gary M Brittenham, MD, James A. Wolff Professor of Pediatrics and Professor of Medicine, Columbia University: Sickle Cell Disease; Acute Chest Syndrome; Respiratory Complication; Vitamin D Deficiency
• Additional relevant MeSH terms: Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Acute Chest Syndrome; Respiration Disorders; Anemia; Anemia, Sickle Cell; Anemia, Hemolytic; Anemia, Hemolytic, Congenital; Vitamin D Deficiency; Nutrition Disorders; Deficiency Diseases; Vitamin A Deficiency; Disease; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins; Trientine

Study Results

No Results Posted as of Jun 27, 2022