Sickle Cell DiseasePhase 2ViDAS-2NCT04170348

Daily Vitamin D for Sickle-cell Respiratory Complications

A Phase 2 study testing Daily oral vitamin D3, 3,333 IU and Monthly oral vitamin D3, 100,000 IU in people with Sickle Cell Disease and Anemia, Sickle Cell, run by Columbia University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 3 to 20 years
Conditions the study is for: Sickle Cell Disease, Anemia, Sickle Cell, Anemia, Hemolytic, Congenital
What is being tested?: Daily oral vitamin D3, 3,333 IU and Monthly oral vitamin D3, 100,000 IU
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 58 participants
Where: 1 siteUnited States
Study dates: 15 Sep 2020to 18 Jun 2024
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 3 to 20 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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

Who cannot join

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

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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

Trial locations and contacts

1 site in 1 country.

United States1 site

Columbia University Medical Center
New York, New York, 10032

Other trials in United States

About this study

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).

Read the 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.

Conditions: Sickle Cell Disease, Anemia, Sickle Cell, Anemia, Hemolytic, Congenital, Respiratory Tract Diseases, Respiration Disorders, Acute Chest Syndrome
Being tested: Daily oral vitamin D3, 3,333 IU, Monthly oral vitamin D3, 100,000 IU, Placebo oral tablet
Keywords: Sickle Cell Disease, Acute Chest Syndrome, Respiratory Complication, Vitamin D Deficiency
Medical subject headings: Anemia, Sickle Cell, Anemia, Hemolytic, Congenital, Respiratory Tract Diseases, Respiration Disorders, Acute Chest Syndrome, Lung Diseases, Asthma, Respiratory Tract Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Daily oral vitamin D3, 3,333 IUDrug
Also called Cholecalciferol for oral administration
Oral vitamin D3, 3,333 IU, will be administered daily.
Monthly oral vitamin D3, 100,000 IUDrug
Also called Cholecalciferol for oral administration
Oral vitamin D3, 100,000 IU, will be administered monthly.
Placebo oral tabletDrug
Participants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month.

Study groups in NCT04170348
Study group	Role	What they receive
Daily oral vitamin D3	Experimental	Oral vitamin D3, 3,333 IU Receives: Drug: Daily oral vitamin D3, 3,333 IU
Monthly bolus oral vitamin D3	Active comparator	Bolus oral vitamin D3, 100,000 IU Receives: Drug: Monthly oral vitamin D3, 100,000 IU; Drug: Placebo oral tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Month 12, Month 24

Secondary outcomes (9)

Mean Forced Vital Capacity (FVC % Predicted)
This is to measure the forced vital capacity (FVC; % predicted) at baseline and at month 24.
Forced Vital Capacity (FVC) is a key measure of lung function that indicates the total volume of air a person can forcefully exhale after taking a deep breath. It is calculated using spirometry, which assesses lung capacity and helps diagnose respiratory conditions. Predicted FVC: The FVC is compared to predicted values based on age, height, and sex to determine if it is within the normal range (80% or more of predicted). Interpretation: A low FVC may indicate obstruction (e.g., asthma or COPD), while a high FVC may suggest restriction in lung function. Baseline Measurement: It is essential to establish a baseline FVC to monitor changes over time and assess the effectiveness of treatments. For accurate interpretation, it is crucial to compare FVC results with other measurements, such as FEV1, to identify the presence of obstructive or restrictive lung disease.
Measured: Baseline, Month 24
Forced Expiratory Volume in 1 Second (FEV1)
Forced Expiratory Volume in 1 second (FEV1; % predicted) at baseline and at month 24.
Measured: Baseline, Month 24
Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity Ratio
Forced Expiratory Volume in 1 second (FEV1; % predicted)/Forced Vital Capacity (FVC) [FEV1/FVC] % predicted at baseline and month 24
Measured: Baseline, Month 24
Forced Expiratory Flow at 25%-75% Vital Capacity (FEF25-75, % Predicted)
Forced Expiratory Flow at 25%-75% vital capacity (FEF25-75) % predicted at baseline and month 24 .
Measured: Baseline, Month 24
Ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)
Ratio of Residual Lung Volume (RV) to Total Lung Capacity (RV/TLC) at baseline and month 24.
Measured: Baseline, Month 24
Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO; % predicted) at baseline and month 24
Measured: Baseline, Month 24
Neutrophil Count
Blood Neutrophil Count in percentage at baseline, month 12 and month 24
Measured: Baseline, Month 12, Month 24
Platelet Count
Blood Platelet Count (Platelets*10^3/ per μL) at baseline, month 12 and month 24
Measured: Baseline, Month 12, Month 24
Serum C-reactive Protein (CRP)
Serum C-reactive protein (CRP; mg/L) at baseline, month 12 and month 24
Measured: Baseline, Month 12, Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Sep 202018 Jun 2024

First posted20 Nov 2019
Study start15 Sep 2020
Primary completion18 Jun 2024
Study completion18 Jun 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
More trials run by Columbia UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Model description: Controlled, double-masked, randomized Phase 2 clinical trial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 58 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04170348
Sponsor's protocol ID: AAAS0396
Other IDs: R01FD006372
Acronym: ViDAS-2
Status last verified: Sep 2025
First submitted: 1 Oct 2019
Last updated: 24 Sep 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
PubMed 29712666
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.
PubMed 29668535
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.
PubMed 33885042

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

All Sickle Cell Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 24 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Daily Vitamin D for Sickle-cell Respiratory Complications
ClinicalTrials.gov ID: NCT04170348
Acronym / sponsor ID: ViDAS-2 / AAAS0396
Conditions: Sickle Cell Disease, Anemia, Sickle Cell, Anemia, Hemolytic, Congenital, Respiratory Tract Diseases, Respiration Disorders, Acute Chest Syndrome
Keywords: Sickle Cell Disease, Acute Chest Syndrome, Respiratory Complication, Vitamin D Deficiency
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 58 participants (actual)
Lead sponsor: Columbia UniversityUniversity, hospital or other
Collaborators: FDA Office of Orphan Products Development
Study start: 15 Sep 2020 (actual)
Primary completion: 18 Jun 2024 (actual)
Study completion: 18 Jun 2024 (actual)
First posted: 20 Nov 2019 (actual)
Results: Posted 24 Sep 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is funded by the FDA Office of Orphan Products Development (OOPD).

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Controlled, double-masked, randomized Phase 2 clinical trial

Arm	Type	Receives
Daily oral vitamin D3	Experimental	Drug: Daily oral vitamin D3, 3,333 IUOral vitamin D3, 3,333 IU
Monthly bolus oral vitamin D3	Active comparator	Drug: Monthly oral vitamin D3, 100,000 IU, Drug: Placebo oral tabletBolus oral vitamin D3, 100,000 IU

Who may qualify

Ages: 3 to 20 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (11 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Daily oral vitamin D3, 3,333 IUAlso: Cholecalciferol for oral administrationOral vitamin D3, 3,333 IU, will be administered daily.	Drug	Daily oral vitamin D3
Monthly oral vitamin D3, 100,000 IUAlso: Cholecalciferol for oral administrationOral vitamin D3, 100,000 IU, will be administered monthly.	Drug	Monthly bolus oral vitamin D3
Placebo oral tabletParticipants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month.	Drug	Monthly bolus oral vitamin D3

Primary outcome

Annual Rate of Respiratory Events
Time frame: Month 12, Month 24
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.

9 secondary outcomes

Mean Forced Vital Capacity (FVC % Predicted)
Time frame: Baseline, Month 24
Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Baseline, Month 24
Forced Expiratory Volume in 1 Second (FEV1)/Forced Vital Capacity Ratio
Time frame: Baseline, Month 24
Forced Expiratory Flow at 25%-75% Vital Capacity (FEF25-75, % Predicted)
Time frame: Baseline, Month 24
Ratio of Residual Lung Volume (RV) to Total Lung Capacity (TLC)
Time frame: Baseline, Month 24
Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Time frame: Baseline, Month 24
Neutrophil Count
Time frame: Baseline, Month 12, Month 24
Platelet Count
Time frame: Baseline, Month 12, Month 24
Serum C-reactive Protein (CRP)
Time frame: Baseline, Month 12, Month 24

Results and safety

Results posted to the registry on 24 Sep 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Daily Oral Vitamin D3	27	22
Monthly Bolus Oral Vitamin D3	31	23

Primary outcome: Annual Rate of Respiratory Events

Time frame: Month 12, Month 24. Mean (Standard Deviation). Unit: Respiratory events per year

Measure	Daily Oral Vitamin D3 n = 27	Monthly Bolus Oral Vitamin D3 n = 31
Treatment Year 1	3.3 (2.1)	3.3 (2.6)
Treatment Year 2	3.4 (1.7)	3.2 (2.4)

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 2 years. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Daily Oral Vitamin D3	8 of 27 (29.6%)	23 of 27 (85.2%)	0 of 27
Monthly Bolus Oral Vitamin D3	3 of 31 (9.7%)	19 of 31 (61.3%)	0 of 31

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 29712666Lee 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.
Background: PubMed 29668535Williams 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.
Background: PubMed 33885042De 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.
Individual participant dataSharing planned: No

Related trials for Sickle Cell Disease

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
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RecruitingObservational study
HPC Offered for PRESERVE Expansion
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RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
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RecruitingPhase 4
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Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gary M Brittenham, MD study chair

Columbia University

Margaret T Lee, MD principal investigator

Columbia University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annual Rate of Respiratory Events (time frame: Month 12, Month 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04170348, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2025.