Back to results

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

Primary Purpose

Sickle Cell Disease, Anemia, Sickle Cell, Anemia, Hemolytic, Congenital

Status

Active

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Daily oral vitamin D3, 3,333 IU

Bolus oral vitamin D3, 100,000 IU

Placebo oral tablet

About this trial

This is an interventional prevention trial for Sickle Cell Disease focused on measuring Sickle Cell Disease, Acute Chest Syndrome, Respiratory Complication, Vitamin D Deficiency

Eligibility Criteria

3 Years - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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

Sites / Locations

Columbia University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Daily oral vitamin D3

Monthly bolus oral vitamin D3

Arm Description

Oral vitamin D3, 3,333 IU

Bolus oral vitamin D3, 100,000 IU

Outcomes

Primary Outcome Measures

Rate of Respiratory Events

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

Change in Forced Vital Capacity (FVC)

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

Change in Forced Expiratory Volume in 1 second (FEV1)

Change in Forced Expiratory Volume in 1 second (FEV1; % predicted) from baseline.

Change in Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity ratio

Change in Forced Expiratory Volume in 1 second (FEV1; % predicted)/Forced Vital Capacity (FVC) [FEV1/FVC] % predicted from baseline.

Change in Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75)

Change in Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75) % predicted from baseline.

Change in ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)

Change in per cent of the ratio of Residual Lung Volume (RV) to Total Lung Capacity (RV/TLC) from baseline.

Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)

Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO; % predicted) from baseline

Change in Fractional Concentration of Exhaled Nitric Oxide (FENO)

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

Change in Maximum Inspiratory Pressure (MIP)

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

Change in Maximum Expiratory Pressure (MEP)

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

Change in interleukin 2 (IL 2) concentration

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

Change in interleukin 4 (IL 4) concentration

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

Change in interleukin 5 (IL 5) concentration

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

Change in interleukin 13 (IL 13) concentration

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

Change in interferon gamma (IFN gamma). concentration

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

Change in interleukin 10 (IL 10) concentration

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

Change in Transforming Growth Factor beta (TGF beta)

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

Change in blood hemoglobin concentration (Hb)

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

Change in blood platelet concentration

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

Change in serum C-reactive protein (CRP)

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

Change in interleukin 1alpha (IL 1alpha) concentration

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

Change in interleukin 1beta (IL 1beta) concentration

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

Change in Tumor Necrosis Factor alpha (TNF alpha) concentration

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

Change in C-terminal telopeptides of Type I collagen (CTX)

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

Change in intact N-terminal propeptide of type I procollagen (P1NP)

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

Full Information

NCT ID

NCT04170348

First Posted

October 1, 2019

Last Updated

September 30, 2023

Sponsor

Gary M Brittenham, MD

1. Study Identification

Unique Protocol Identification Number

NCT04170348

Brief Title

Daily Vitamin D for Sickle-cell Respiratory Complications

Acronym

ViDAS-2

Official Title

Daily Vitamin D for Sickle-cell Respiratory Complications

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 15, 2020 (Actual)

Primary Completion Date

June 30, 2024 (Anticipated)

Study Completion Date

February 28, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Gary M Brittenham, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Controlled, double-masked, randomized Phase 2 clinical trial

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Masking will be performed by the Research Pharmacy; all other research staff and participants will be blinded to allocation.

Allocation

Randomized

Enrollment

69 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Daily oral vitamin D3

Arm Type

Experimental

Arm Description

Oral vitamin D3, 3,333 IU

Arm Title

Monthly bolus oral vitamin D3

Arm Type

Active Comparator

Arm Description

Bolus oral vitamin D3, 100,000 IU

Intervention Type

Drug

Intervention Name(s)

Daily oral vitamin D3, 3,333 IU

Other Intervention Name(s)

Cholecalciferol for oral administration, 10-secocholeta-5,7,10(19)-trien-3B-ol for oral administration

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Bolus oral vitamin D3, 100,000 IU

Other Intervention Name(s)

Cholecalciferol for oral administration, 10-secocholeta-5,7,10(19)-trien-3B-ol for oral administration

Intervention Description

Bolus oral vitamin D3, 100,000 IU, will be administered monthly.

Intervention Type

Drug

Intervention Name(s)

Placebo oral tablet

Intervention Description

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

Primary Outcome Measure Information:

Title

Rate of Respiratory Events

Description

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.

Time Frame

Screening up to month 24

Secondary Outcome Measure Information:

Title

Change in Forced Vital Capacity (FVC)

Description

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

Time Frame

Baseline and month 24

Title

Change in Forced Expiratory Volume in 1 second (FEV1)

Description

Change in Forced Expiratory Volume in 1 second (FEV1; % predicted) from baseline.

Time Frame

Baseline and month 24

Title

Change in Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity ratio

Description

Change in Forced Expiratory Volume in 1 second (FEV1; % predicted)/Forced Vital Capacity (FVC) [FEV1/FVC] % predicted from baseline.

Time Frame

Baseline and month 24

Title

Change in Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75)

Description

Change in Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75) % predicted from baseline.

Time Frame

Baseline and month 24

Title

Change in ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)

Description

Change in per cent of the ratio of Residual Lung Volume (RV) to Total Lung Capacity (RV/TLC) from baseline.

Time Frame

Baseline and month 24

Title

Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)

Description

Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO; % predicted) from baseline

Time Frame

Baseline and month 24

Title

Change in Fractional Concentration of Exhaled Nitric Oxide (FENO)

Description

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

Time Frame

Baseline and month 24

Title

Change in Maximum Inspiratory Pressure (MIP)

Description

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

Time Frame

Baseline and month 24

Title

Change in Maximum Expiratory Pressure (MEP)

Description

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

Time Frame

Baseline and month 24

Title

Change in interleukin 2 (IL 2) concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in interleukin 4 (IL 4) concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in interleukin 5 (IL 5) concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in interleukin 13 (IL 13) concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in interferon gamma (IFN gamma). concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in interleukin 10 (IL 10) concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in Transforming Growth Factor beta (TGF beta)

Description

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

Time Frame

Baseline up to month 24

Title

Change in blood hemoglobin concentration (Hb)

Description

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

Time Frame

Baseline up to month 24

Title

Change in blood platelet concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in serum C-reactive protein (CRP)

Description

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

Time Frame

Baseline up to month 24

Title

Change in interleukin 1alpha (IL 1alpha) concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in interleukin 1beta (IL 1beta) concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in Tumor Necrosis Factor alpha (TNF alpha) concentration

Description

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

Time Frame

Baseline up to month 24

Title

Change in C-terminal telopeptides of Type I collagen (CTX)

Description

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

Time Frame

Baseline up to month 24

Title

Change in intact N-terminal propeptide of type I procollagen (P1NP)

Description

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

Time Frame

Baseline up to month 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

3 Years

Maximum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gary M Brittenham, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Margaret T Lee, MD

Organizational Affiliation

Columbia University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Columbia University Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

29712666

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.

Results Reference

background

PubMed Identifier

29668535

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.

Results Reference

background

PubMed Identifier

33885042

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.

Results Reference

background

Links:

URL

https://journals.lww.com/jpho-online/Abstract/2018/08000/Response_to_Long_term_Vitamin_D_Therapy_for_Bone.8.aspx

Description

Response to Long-term Vitamin D Therapy for Bone Disease in Children With Sickle Cell Disease.

URL

https://ashpublications.org/bloodadvances/article/2/9/969/15839/Randomized-phase-2-trial-of-monthly-vitamin-D-to

Description

Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease

Learn more about this trial

Daily Vitamin D for Sickle-cell Respiratory Complications

We'll reach out to this number within 24 hrs