Asthma, Pediatric Obesity, Vitamin D Deficiency
Conditions
Keywords
pediatric obesity
Brief summary
The overall objective of the study is to determine the pharmacokinetics of Vitamin D supplementation in children who have asthma and are overweight or obese.
Detailed description
This study has two parts. In part 1, study participants will be randomized to receive one of four doses of vitamin D supplementation in international units (IU) over at 16-week period: 1) Single 50,000 IU loading dose + 6000 IU daily dose; 2) Single 50,000 IU loading dose + 10,000 IU daily dose: 3) 6000 IU daily dose; or 4) 600 IU daily dose. Based on pharmacokinetic analysis, one of the doses (1-3) will be selected to use in part 2. In part 2, study participants will be randomized to the dose selected in part 1 or the 600 IU daily dose of vitamin D supplementation to be administered over a 16-week dosing period. Across both parts, safety of each dose regimen of vitamin D supplementation will be evaluated, and the effectiveness of each dose to achieve a serum level of 25(OH)D greater than or equal to 40 ng/ml will be assessed.
Interventions
DIETARY_SUPPLEMENTVitamin D3 oral regimen
Vitamin D3 oral regimens supplementation
Sponsors
National Institutes of Health (NIH)
IDeA States Pediatric Clinical Trials Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Randomized, parallel arm clinical trial 4 arms in part 1 2 arms in part 2
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Body mass index greater than or equal to 85% for age and sex * Physician-diagnosed asthma * Ongoing relationship with asthma provider responsible for asthma care * Serum 25(OH) D level 10 ng/ml to less than 30 ng/ml at screening visit based on local laboratory test * Ability to swallow pills similar in size to the vitamin D preparation to be used * Signed consent form from parent, legal guardian or caregiver and signed assent from participant (as appropriate) * Females of childbearing years must not be pregnant, must not be lactating and must agree to practice adequate birth control method * Child and parent, legal guardian, or caregiver must speak English or Spanish
Exclusion criteria
* Known diseases of calcium metabolism or the parathyroid * History of renal insufficiency or kidney stones * Known liver failure or history of abnormal liver function tests * History of Williams syndrome, sarcoidosis, or granulomatous disease * Active tuberculosis * Spot urine calcium/creatinine ration greater than 0.37 (calcium and creatinine measured in mg/ml). This can be repeated following adequate hydration * Clinical evidence of rickets * Taking supplemental vitamin D greater than equal to 1000 IU per day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Optimal Dosing Level to Use in Part 2 | 20 weeks | Determine the best vitamin D supplementation level based on PK analysis of participants enrolled in Part 1. The PK of 25(OH)D after vitamin D supplementation in children will be characterized using a 2-compartment population PK model (popPK) with linear absorption and elimination kinetics. |
| Part 2: Proportion of Participants With Vitamin D Levels >= 40 ng/ml | 16 weeks | Proportion of participants in part 2 who achieve vitamin levels \>= 40 ng/ml |
Countries
United States
Participant flow
Recruitment details
A total of 166 study participants consented to be screened for the trial; 112 met eligibility criteria and were randomized onto the trial. The trial comprised of a Dose Finding part (Part 1) and a Dose Confirming par (Part 2). During Part 1, participants (children) were enrolled and randomized to one of four dose groups at 1:1:1:1 allocation ratio. During Part 2, participants (children) were randomized to one of two dose groups at 2:1 allocation ratio.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Cohort 1 Vitamin D3 Oral Regimen Intervention: Vitamin D: Single 50,000 IU loading dose + 6000 IU daily dose
Vitamin D3 oral regimen: Vitamin D3 oral regimens supplementation | 13 |
| Part 1, Cohort 2 Vitamin D3 Oral Regimen Vitamin D: Single 50,000 IU loading dose + 10,000 IU daily dose
Vitamin D3 oral regimen: Vitamin D3 oral regimens supplementation | 12 |
| Part 1, Cohort 3 Vitamin D3 Oral Regimen Vitamin D: 6000 IU daily dose
Vitamin D3 oral regimen: Vitamin D3 oral regimens supplementation | 11 |
| Part 1, Cohort 4 Vitamin D3 Oral Regimen Vitamin D: 600 IU daily dose
Vitamin D3 oral regimen: Vitamin D3 oral regimens supplementation | 12 |
| Part 2, Cohort A Vitamin D3 Oral Regimen Vitamin D: Single 50,000 IU loading dose + 8,000 IU daily dose
Vitamin D3 oral regimen: Vitamin D3 oral regimens supplementation | 43 |
| Part 2, Cohort B Vitamin D Oral Regimen Vitamin D: 600 IU daily dose
Vitamin D3 oral regimen: Vitamin D3 oral regimens supplementation | 21 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Part 1, Cohort 1 Vitamin D3 Oral Regimen | Part 1, Cohort 2 Vitamin D3 Oral Regimen | Part 1, Cohort 3 Vitamin D3 Oral Regimen | Part 1, Cohort 4 Vitamin D3 Oral Regimen | Part 2, Cohort A Vitamin D3 Oral Regimen | Part 2, Cohort B Vitamin D Oral Regimen |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 12.1 years STANDARD_DEVIATION 2.8 | 12.8 years STANDARD_DEVIATION 3.1 | 12.3 years STANDARD_DEVIATION 3.4 | 11.5 years STANDARD_DEVIATION 3.6 | 12.5 years STANDARD_DEVIATION 2.9 | 12.2 years STANDARD_DEVIATION 2.5 | 11.7 years STANDARD_DEVIATION 2.6 |
| Baseline 25(OH)D | 18.0 ng/mL STANDARD_DEVIATION 6 | 18.3 ng/mL STANDARD_DEVIATION 6.5 | 20.8 ng/mL STANDARD_DEVIATION 7.2 | 19.0 ng/mL STANDARD_DEVIATION 5.2 | 17.6 ng/mL STANDARD_DEVIATION 5.8 | 17.7 ng/mL STANDARD_DEVIATION 6 | 16.3 ng/mL STANDARD_DEVIATION 5.2 |
| Baseline 25(OH)D level > 100 ng/mL No | 109 Participants | 12 Participants | 12 Participants | 11 Participants | 12 Participants | 42 Participants | 20 Participants |
| Baseline 25(OH)D level > 100 ng/mL Yes | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline Body Mass Index (BMI) | 31.0 kg/m^2 STANDARD_DEVIATION 7.3 | 33.9 kg/m^2 STANDARD_DEVIATION 8.4 | 29.7 kg/m^2 STANDARD_DEVIATION 6.4 | 30.1 kg/m^2 STANDARD_DEVIATION 4.3 | 32.2 kg/m^2 STANDARD_DEVIATION 9.2 | 30.8 kg/m^2 STANDARD_DEVIATION 6.9 | 30.3 kg/m^2 STANDARD_DEVIATION 8.2 |
| BMI percentile >= 85th to < 95th | 24 Participants | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 9 Participants | 5 Participants |
| BMI percentile >= 95th to < 99th | 36 Participants | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 16 Participants | 8 Participants |
| BMI percentile >= 99th | 52 Participants | 6 Participants | 7 Participants | 7 Participants | 6 Participants | 18 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 5 Participants | 2 Participants | 2 Participants | 1 Participants | 7 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 86 Participants | 7 Participants | 10 Participants | 8 Participants | 10 Participants | 33 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 6 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 45 Participants | 6 Participants | 4 Participants | 5 Participants | 6 Participants | 15 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 4 Participants | 5 Participants | 3 Participants | 5 Participants | 19 Participants | 10 Participants |
| Rural-Urban Commuting Area (RUCA) codes Metropolitan | 92 Participants | 13 Participants | 10 Participants | 9 Participants | 11 Participants | 32 Participants | 17 Participants |
| Rural-Urban Commuting Area (RUCA) codes Micropolitan | 8 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 5 Participants | 1 Participants |
| Rural-Urban Commuting Area (RUCA) codes Rural | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants |
| Rural-Urban Commuting Area (RUCA) codes Small town | 8 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 53 Participants | 6 Participants | 7 Participants | 5 Participants | 5 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Male | 59 Participants | 7 Participants | 5 Participants | 6 Participants | 7 Participants | 23 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 12 | 0 / 11 | 0 / 12 | 0 / 43 | 0 / 21 |
| other Total, other adverse events | 11 / 13 | 9 / 12 | 11 / 11 | 10 / 12 | 21 / 43 | 14 / 21 |
| serious Total, serious adverse events | 0 / 13 | 1 / 12 | 1 / 11 | 1 / 12 | 0 / 43 | 1 / 21 |
Outcome results
Primary
Part 1: Optimal Dosing Level to Use in Part 2
Determine the best vitamin D supplementation level based on PK analysis of participants enrolled in Part 1. The PK of 25(OH)D after vitamin D supplementation in children will be characterized using a 2-compartment population PK model (popPK) with linear absorption and elimination kinetics.
Time frame: 20 weeks
Population: A total of 263 PK samples from 48 participants were collected in part 1 of the VDORA1 study. For the population PK analysis, 36 samples with missing prior dosing information from 13 participants were excluded, leaving a final analysis population of 44 participants with 227 serum concentrations.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vitamin D3 Oral Regimen | Part 1: Optimal Dosing Level to Use in Part 2 | Daily Dose (IU) | 8000 IU |
| Vitamin D3 Oral Regimen | Part 1: Optimal Dosing Level to Use in Part 2 | Single Loading Dose (IU) | 50000 IU |
Comparison: Part 1 of this study was to perform a population PK analysis of 25(OH)D after oral administration of Vitamin D in children who are overweight or obese and have asthma. Based on the interim analysis of the VDORA study, the PK of 25(OH)D after Vitamin D supplementation in children was well characterized by a 2-compartment population PK model with linear absorption and elimination kinetics. A loading dose of 50,000 IU followed by a daily dose of 8,000 IU was recommended.
Primary
Part 2: Proportion of Participants With Vitamin D Levels >= 40 ng/ml
Proportion of participants in part 2 who achieve vitamin levels \>= 40 ng/ml
Time frame: 16 weeks
Population: One participant from Cohort A and three participants from Cohort B did not have 25(OH)D measurements at Visit 6 (week 16).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin D3 Oral Regimen | Part 2: Proportion of Participants With Vitamin D Levels >= 40 ng/ml | 0.786 proportion of participants |
| Part 2, Cohort B Vitamin D Oral Regimen | Part 2: Proportion of Participants With Vitamin D Levels >= 40 ng/ml | 0 proportion of participants |
Comparison: This is a one-sample test of proportion.p-value: 0.0001z-test