Asthma
Conditions
Keywords
asthma, vitamin D
Brief summary
This study of vitamin D is designed to assess both the safety and efficacy of potential doses (2,000 IU/day and 4,000 IU/day) in raising a vitamin D level to a normal range in a short period of time (e.g. 4 weeks or less) compared to 200 IU/day. In children with vitamin D insufficiency or deficiency who are at risk for severe asthma exacerbations, we hypothesize that both vitamin D supplementation with 4,000 IU/day and 2,000 IU/day will safely achieve normal vitamin D levels, but that the higher dose (4,000 IU/day) will result in a larger proportion of subjects achieving this level at 4 and 8 weeks.
Detailed description
Asthma is a major public health problem in the United States and worldwide. Severe disease exacerbations account for the majority of costs attributable to asthma in the United States. Vitamin D is an essential nutrient with significant immuno-modulatory effects. The observation that vitamin D insufficiency and asthma share risk factors such as urban residence, obesity, and African American ethnicity has generated significant interest in exploring a link between these two conditions. This is an 8-week randomized, double-masked, controlled trial of vitamin D3 (2,000 IU/day and 4,000 IU/day) to achieve vitamin D sufficiency (a serum 25(OH)D ≥30 ng/ml in 60 school-aged children (ages 6 to 14 years) who have vitamin D insufficiency (a serum 25(OH)D \<30 ng/ml) and are at risk for severe asthma exacerbations, but whose asthma that is well-controlled on medium-dose inhaled corticosteroid (ICS) at the end of a 4-week run-in period.
Interventions
DIETARY_SUPPLEMENTCholecalciferol
vitamin D supplementation with either 2,000 IU/day or 4,000 IU/day compared to vitamin D3 supplementation with 200 IU/day.
Sponsors
University of Pittsburgh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 14 Years
Healthy volunteers
No
Inclusion criteria
* Be at least 6 years of age and younger than 15 years of age * Have physician-diagnosed asthma * Taking a medium dose of ICS (e.g. fluticasone 220mcg BID) for daily asthma control for at least 6 months in the prior year. * Have had a severe asthma exacerbation in the previous year, defined as an Emergency Department (ED) visit, hospitalization, or unscheduled clinic visit for asthma resulting in intramuscular, intravenous, or oral steroids. * Have bronchodilator responsiveness (BDR, an increase in FEV1 ≥12% from baseline after administration of inhaled albuterol) or (if no BDR) increased airway responsiveness to methacholine challenge * Have vitamin D insufficiency (a serum vitamin D (25(OH)D) level \<30 ng/ml) * Have his/her parents give voluntary written consent to participate in the study
Exclusion criteria
* Chronic respiratory disorder other than asthma (e.g., bronchiectasis). * Severe asthma, as evidenced by any of the following: a) chronic need for medication other than single controller therapy and inhaled β2-agonist, b) intubation for asthma at any time, and c) ≥2 hospitalizations or ≥6 severe asthma exacerbations in the previous year * History of cigarette smoking in the prior year or former smoking if ≥5 pack-years * Hepatic or renal disease, metabolic rickets, malabsorptive disorders, or other chronic diseases that would affect vitamin D metabolism * Immune deficiency, cleft palate or Down's syndrome, which might increase the child's likelihood of respiratory infections * Treatment with anticonvulsants or pharmacological doses of vitamin D (≥1,000 IU/day of vitamin D2 or D3) * Chronic oral corticosteroid therapy * Inability to perform acceptable spirometry * Use of investigational therapies or participation in clinical trials 30 days before or during the duration of the study * Serum calcium \>10.8 mg/dl * Serum 25(OH) D \<10 ng/ml (severe vitamin D deficiency)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Sufficient Vitamin D Levels (≥30 ng/ml) After 8 Weeks of Supplementation | 8 weeks | The primary outcome of the proposed trial will be a sufficient (≥30 ng/ml) vitamin D level after 8 weeks of supplementation |
| Number of Participants With Vitamin D Sufficiency (Vitamin D ≥30 ng/ml) After 4 Weeks of Supplementation | 4 weeks | The outcome is defined as the number of participants with a sufficient (≥30 ng/ml) vitamin D level after 8 weeks of supplementation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Vitamin D Toxicity | 8 weeks | Participants with vitamin D toxicity, hypercalcemia (\>10.8mg/dl) and/or an elevated urine Ca/Cr ratio (\>0.37) |
| Number of Participants With Elevated Urinary Calcium/Creatinine Ratio | 4 and/or 8 weeks | Elevated urinary calcium/creatinine ratio defined as UCa/UCr \> 0.37 after either 4 weeks or 8 weeks of supplementation |
| Number of Participants With FEV1 < 80% of Predicted | 8 weeks | Forced expiratory volume in 1 second (FEV1) as percent predicted (with reference values used according to the child's age, gender and ethnicity). |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from: 1) the Emergency Department of Children's Hospital of Pittsburgh (CHP), 2) the Pulmonary Medicine and Allergy clinics of CHP, 3) the General Pediatric Clinics of CHP, and 4) participants in a prior study of the Pediatric Environmental Medicine Center of CHP (who had consented to be contacted about studies of asthma).
Pre-assignment details
We recruited 48 children who met initial inclusion/exclusion criteria. Of these 48 children, 20 were excluded because of a 25(OH)D ≥30 ng/ml (n=13) or lack of bronchodilator response or airway responsiveness (n=7) at visit 1. Of the 28 remaining children, 4 were excluded because of non-adherence or poor asthma control during the run-in period.
Participants by arm
| Arm | Count |
|---|---|
| Cholecalciferol 4000 IU Cholecalciferol 4000 IU oral chewable tablet once daily for 8 weeks | 8 |
| Cholecalciferol 2000 IU Cholecalciferol 2000 IU oral chewable tablet once daily for 8 weeks | 8 |
| Cholecalciferol 200 IU Cholecalciferol 200 IU oral chewable tablet once daily for 8 weeks | 8 |
| Total | 24 |
Baseline characteristics
| Characteristic | Cholecalciferol 4000 IU | Cholecalciferol 2000 IU | Cholecalciferol 200 IU | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 8 Participants | 8 Participants | 24 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic/Others | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 6 participants | 6 participants | 2 participants | 14 participants |
| Race/Ethnicity, Customized Non-Hispanic white | 2 participants | 2 participants | 5 participants | 9 participants |
| Region of Enrollment United States | 8 participants | 8 participants | 8 participants | 24 participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With Sufficient Vitamin D Levels (≥30 ng/ml) After 8 Weeks of Supplementation
The primary outcome of the proposed trial will be a sufficient (≥30 ng/ml) vitamin D level after 8 weeks of supplementation
Time frame: 8 weeks
Population: In this pilot study, we wanted to report and compare the proportion of subjects who achieved vitamin D sufficiency after 8 weeks of treatment with one of three vitamin D doses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cholecalciferol 4000 IU | Number of Participants With Sufficient Vitamin D Levels (≥30 ng/ml) After 8 Weeks of Supplementation | 8 participants |
| Cholecalciferol 2000 IU | Number of Participants With Sufficient Vitamin D Levels (≥30 ng/ml) After 8 Weeks of Supplementation | 6 participants |
| Cholecalciferol 200 IU | Number of Participants With Sufficient Vitamin D Levels (≥30 ng/ml) After 8 Weeks of Supplementation | 4 participants |
Primary
Number of Participants With Vitamin D Sufficiency (Vitamin D ≥30 ng/ml) After 4 Weeks of Supplementation
The outcome is defined as the number of participants with a sufficient (≥30 ng/ml) vitamin D level after 8 weeks of supplementation
Time frame: 4 weeks
Population: The characteristics of the study population are the same as described for the other primary outcome (vitamin D sufficiency at 8 weeks)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cholecalciferol 4000 IU | Number of Participants With Vitamin D Sufficiency (Vitamin D ≥30 ng/ml) After 4 Weeks of Supplementation | 6 participants |
| Cholecalciferol 2000 IU | Number of Participants With Vitamin D Sufficiency (Vitamin D ≥30 ng/ml) After 4 Weeks of Supplementation | 7 participants |
| Cholecalciferol 200 IU | Number of Participants With Vitamin D Sufficiency (Vitamin D ≥30 ng/ml) After 4 Weeks of Supplementation | 4 participants |
Secondary
Number of Participants With Elevated Urinary Calcium/Creatinine Ratio
Elevated urinary calcium/creatinine ratio defined as UCa/UCr \> 0.37 after either 4 weeks or 8 weeks of supplementation
Time frame: 4 and/or 8 weeks
Population: We wanted to compare the proportion of subjects who had an elevated UCa/UCr ratio across the three groups in this pilot Phase I Study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cholecalciferol 4000 IU | Number of Participants With Elevated Urinary Calcium/Creatinine Ratio | 0 participants |
| Cholecalciferol 2000 IU | Number of Participants With Elevated Urinary Calcium/Creatinine Ratio | 0 participants |
| Cholecalciferol 200 IU | Number of Participants With Elevated Urinary Calcium/Creatinine Ratio | 0 participants |
Secondary
Number of Participants With FEV1 < 80% of Predicted
Forced expiratory volume in 1 second (FEV1) as percent predicted (with reference values used according to the child's age, gender and ethnicity).
Time frame: 8 weeks
Population: We wanted to compare the proportion of subjects whose FEV1 % predicted fell below 80% predicted across the three arms in this pilot Phase I study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cholecalciferol 4000 IU | Number of Participants With FEV1 < 80% of Predicted | 0 participants |
| Cholecalciferol 2000 IU | Number of Participants With FEV1 < 80% of Predicted | 0 participants |
| Cholecalciferol 200 IU | Number of Participants With FEV1 < 80% of Predicted | 0 participants |
Secondary
Number of Participants With Vitamin D Toxicity
Participants with vitamin D toxicity, hypercalcemia (\>10.8mg/dl) and/or an elevated urine Ca/Cr ratio (\>0.37)
Time frame: 8 weeks
Population: We wanted to report and compare the proportion of subjects who had vitamin D toxicity, hypercalcemia or an elevated UCa/UCr ratio across the three treatment arms
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cholecalciferol 4000 IU | Number of Participants With Vitamin D Toxicity | 0 participants |
| Cholecalciferol 2000 IU | Number of Participants With Vitamin D Toxicity | 0 participants |
| Cholecalciferol 200 IU | Number of Participants With Vitamin D Toxicity | 0 participants |