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| ID | Type | Description | Link |
|---|---|---|---|
| R01FD006372 | U.S. FDA Grant/Contract | View source |
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| Name | Class |
|---|---|
| FDA Office of Orphan Products Development | FED |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Daily oral vitamin D3 | Experimental | Oral vitamin D3, 3,333 IU |
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| Monthly bolus oral vitamin D3 | Active Comparator | Bolus oral vitamin D3, 100,000 IU |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daily oral vitamin D3, 3,333 IU | Drug | Oral vitamin D3, 3,333 IU, will be administered daily. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | Month 12, Month 24 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gary M Brittenham, MD | Columbia University | Study Chair |
| Margaret T Lee, MD | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Columbia University Medical Center | New York | New York | 10032 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29712666 | Background | 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. | |
| 29668535 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Daily Oral Vitamin D3 | Oral vitamin D3, 3,333 IU Daily oral vitamin D3, 3,333 IU: Oral vitamin D3, 3,333 IU, will be administered daily. |
| FG001 | Monthly Bolus Oral Vitamin D3 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 29, 2022 |
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Controlled, double-masked, randomized Phase 2 clinical trial
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Masking will be performed by the Research Pharmacy; all other research staff and participants will be blinded to allocation.
| Monthly oral vitamin D3, 100,000 IU | Drug | Oral vitamin D3, 100,000 IU, will be administered monthly. |
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| Placebo oral tablet | Drug | Participants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month. |
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| Baseline, Month 24 |
| Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second (FEV1; % predicted) at baseline and at month 24. | 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 | 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 . | 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. | 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 | Baseline, Month 24 |
| Neutrophil Count | Blood Neutrophil Count in percentage at baseline, month 12 and month 24 | Baseline, Month 12, Month 24 |
| Platelet Count | Blood Platelet Count (Platelets*10^3/ per μL) at baseline, month 12 and month 24 | Baseline, Month 12, Month 24 |
| Serum C-reactive Protein (CRP) | Serum C-reactive protein (CRP; mg/L) at baseline, month 12 and month 24 | Baseline, Month 12, Month 24 |
| 33885042 | Background | 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. |
Bolus oral vitamin D3, 100,000 IU
Bolus oral vitamin D3, 100,000 IU: Bolus oral vitamin D3, 100,000 IU, will be administered monthly.
Placebo oral tablet: Participants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month.
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Daily Oral Vitamin D3 | Oral vitamin D3, 3,333 IU Daily oral vitamin D3, 3,333 IU: Oral vitamin D3, 3,333 IU, will be administered daily. |
| BG001 | Monthly Bolus Oral Vitamin D3 | Bolus oral vitamin D3, 100,000 IU Bolus oral vitamin D3, 100,000 IU: Bolus oral vitamin D3, 100,000 IU, will be administered monthly. Placebo oral tablet: Participants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | Respiratory events per year | Month 12, Month 24 |
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| Secondary | 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. | Due to COVID-19 restrictions, data was only collected/analyzed for 13 out of 27 at baseline and 18 out of 27 at month 24 for DAILY ARM; data was collected/analyzed for 14 out of 31 at baseline and 21 out 31 at month 24 for MONTHLY ARM. | Posted | Mean | Standard Deviation | percent predicted | Baseline, Month 24 |
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| Secondary | Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second (FEV1; % predicted) at baseline and at month 24. | Due to COVID-19 restrictions, data was only collected/analyzed for 13 out of 27 at baseline and 18 out of 27 at month 24 for DAILY ARM; data was collected/analyzed for 14 out of 31 at baseline and 21 out 31 at month 24 for MONTHLY ARM. | Posted | Mean | Standard Deviation | percent predicted | Baseline, Month 24 |
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| Secondary | 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 | Due to COVID-19 restrictions, data was only collected/analyzed for 13 out of 27 at baseline and 18 out of 27 at month 24 for DAILY ARM; data was collected/analyzed for 14 out of 31 at baseline and 21 out 31 at month 24 for MONTHLY ARM. | Posted | Mean | Standard Deviation | ratio | Baseline, Month 24 |
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| Secondary | 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 . | Due to COVID-19 restrictions, data was only collected/analyzed for 13 out of 27 at baseline and 18 out of 27 at month 24 for DAILY ARM; data was collected/analyzed for 14 out of 31 at baseline and 21 out 31 at month 24 for MONTHLY ARM. | Posted | Mean | Standard Deviation | percent predicted | Baseline, Month 24 |
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| Secondary | 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. | Due to COVID-19 restrictions, data was only collected/analyzed for 11 out of 27 at baseline and 16 out of 27 at month 24 for DAILY ARM; data was collected/analyzed for 12 out of 31 at baseline and 18 out 31 at month 24 for MONTHLY ARM. | Posted | Mean | Standard Deviation | ratio | Baseline, Month 24 |
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| Secondary | Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO) | Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO; % predicted) at baseline and month 24 | Due to COVID-19 restrictions, data was only collected/analyzed for 11 out of 27 at baseline and 16 out of 27 at month 24 for DAILY ARM; data was collected/analyzed for 12 out of 31 at baseline and 18 out 31 at month 24 for MONTHLY ARM. | Posted | Mean | Standard Deviation | percent predicted | Baseline, Month 24 |
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| Secondary | Neutrophil Count | Blood Neutrophil Count in percentage at baseline, month 12 and month 24 | Data was collected and analyzed only for the following numbers of study participants out of 27 for DAILY ARM and 31 for MONTHLY ARM at each time point due to some study participants did not complete the study. | Posted | Mean | Standard Deviation | Percentage of Neutrophils | Baseline, Month 12, Month 24 |
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| Secondary | Platelet Count | Blood Platelet Count (Platelets*10^3/ per μL) at baseline, month 12 and month 24 | Data was collected and analyzed only for the following numbers of study participants out of 27 for DAILY ARM and 31 for MONTHLY ARM at each time point due to some study participants did not complete the study. | Posted | Mean | Standard Deviation | Platelets *10^3/ per μL | Baseline, Month 12, Month 24 |
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| Secondary | Serum C-reactive Protein (CRP) | Serum C-reactive protein (CRP; mg/L) at baseline, month 12 and month 24 | Data was collected and analyzed only for the following numbers of study participants out of 27 for DAILY ARM and 31 for MONTHLY ARM at each time point due to some study participants did not complete the study. | Posted | Mean | Standard Deviation | mg/L | Baseline, Month 12, Month 24 |
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Up to 2 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Daily Oral Vitamin D3 | Oral vitamin D3, 3,333 IU Daily oral vitamin D3, 3,333 IU: Oral vitamin D3, 3,333 IU, will be administered daily. | 0 | 27 | 8 | 27 | 23 | 27 |
| EG001 | Monthly Bolus Oral Vitamin D3 | Bolus oral vitamin D3, 100,000 IU Bolus oral vitamin D3, 100,000 IU: Bolus oral vitamin D3, 100,000 IU, will be administered monthly. Placebo oral tablet: Participants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month. | 0 | 31 | 3 | 31 | 19 | 31 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain syndrome | General disorders | Non-systematic Assessment |
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| Splenic sequestration | Surgical and medical procedures | Non-systematic Assessment |
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| Acute chest syndrome | General disorders | Non-systematic Assessment |
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| Bone infection | Infections and infestations | Non-systematic Assessment |
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| Clinical sepsis | Infections and infestations | Non-systematic Assessment |
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| COVID-19 | Infections and infestations | Non-systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain syndrome | General disorders | Non-systematic Assessment |
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| Upper respiratory infection | Infections and infestations | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Margaret T. Lee, Professor of Pediatric | CUIMC | 212-305-6290 | ml653@cumc.columbia.edu |
| Jul 25, 2025 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D000745 | Anemia, Hemolytic, Congenital |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D056586 | Acute Chest Syndrome |
| D008171 | Lung Diseases |
| D001249 | Asthma |
| D012141 | Respiratory Tract Infections |
| D009748 | Nutrition Disorders |
| D001361 | Avitaminosis |
| D014808 | Vitamin D Deficiency |
| ID | Term |
|---|---|
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D001982 | Bronchial Diseases |
| D008173 | Lung Diseases, Obstructive |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D007239 | Infections |
| D009750 | Nutritional and Metabolic Diseases |
| D003677 | Deficiency Diseases |
| D044342 | Malnutrition |
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| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| D000284 | Administration, Oral |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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Bolus oral vitamin D3, 100,000 IU Bolus oral vitamin D3, 100,000 IU: Bolus oral vitamin D3, 100,000 IU, will be administered monthly. Placebo oral tablet: Participants randomized to receive once monthly oral bolus of vitamin D3, will receive placebo on all other days of the month. |
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