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Daily Vitamin D for Sickle-cell Respiratory Complications (ViDAS-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04170348
Recruitment Status : Not yet recruiting
First Posted : November 20, 2019
Last Update Posted : November 20, 2019
Sponsor:
Collaborator:
FDA Office of Orphan Products Development
Information provided by (Responsible Party):
Gary M Brittenham, MD, 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).


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 once a year. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Controlled, 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
Estimated Study Start Date : February 2020
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin D

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.




Primary Outcome Measures :
  1. Rate of Respiratory Events [ Time Frame: 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) [ Time Frame: Baseline up to month 24 ]
    Change forced vital capacity (FVC; % predicted) from baseline

  2. Change in Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: Baseline up to 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 [ Time Frame: Baseline up to 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) [ Time Frame: Baseline up to 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) [ Time Frame: Baseline up to 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) [ Time Frame: Baseline up to 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) [ Time Frame: Baseline up to 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) [ Time Frame: Baseline up to month 24 ]
    Change in Maximum Inspiratory Pressure (MIP; cm H2O) from baseline

  9. Change in Maximum Expiratory Pressure (MEP) [ Time Frame: Baseline up to month 24 ]
    Change in Maximum Expiratory Pressure (MEP; cm H2O) from baseline

  10. Change in interleukin 2 (IL 2) concentration [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Baseline up to month 24 ]
    Change in blood hemoglobin concentration (Hb; g/dL) from baseline

  18. Change in blood platelet concentration [ Time Frame: Baseline up to month 24 ]
    Change in blood platelet concentration (platelets/mL) from baseline

  19. Change in serum C-reactive protein (CRP) [ Time Frame: Baseline up to month 24 ]
    Change in serum C-reactive protein (CRP; mg/L) from baseline

  20. Change in interleukin 1alpha (IL 1alpha) concentration [ Time Frame: Baseline up to month 24 ]
    Change in serum interleukin 1alpha (IL 1alpha; pg/mL) from baseline

  21. Change in interleukin 1beta (IL 1beta) concentration [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Baseline up to month 24 ]
    Chang in serum intact N-terminal propeptide of type I procollagen (P1NP; µg/L) from baseline.=



Information from the National Library of Medicine

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Ages Eligible for Study:   3 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04170348


Contacts
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Contact: Gary M Brittenham, MD 212 305 7005 gmb31@cumc.columbia.edu
Contact: Margaret T Lee, MD 212 305 6290 ml653@cumc.columbia.edu

Locations
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United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Contact: Margaret T Lee, MD    212-305-6290    ml653@cumc.columbia.edu   
Contact: Miriam Rosen    646 317 2070    mr3989@cumc.columbia.edu   
Sub-Investigator: Stephen M Arpadi, MD         
Sub-Investigator: Ilene Fennoy, MD, MPH         
Sub-Investigator: Zhezhen Jin, PhD         
Sub-Investigator: Meyer Kattan, MD, CM         
Sub-Investigator: Rachel Miller, MD         
Sub-Investigator: Jeri Nieves, PhD         
Sponsors and Collaborators
Gary M Brittenham, MD
FDA Office of Orphan Products Development
Investigators
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Principal Investigator: Gary M Brittenham, MD Columbia University
Principal Investigator: Margaret T Lee, MD Columbia University

Additional Information:
Publications:
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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 ( U.S. FDA Grant/Contract )
First Posted: November 20, 2019    Key Record Dates
Last Update Posted: November 20, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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, Columbia University:
Sickle Cell Disease
Acute Chest Syndrome
Respiratory Complication
Vitamin D Deficiency
Additional relevant MeSH terms:
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Respiratory Tract Infections
Lung 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
Respiratory Tract Diseases
Pathologic Processes
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Avitaminosis
Malnutrition
Infection
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents