Asthma, Inflammation, Obesity
Conditions
Keywords
Asthma, Obesity, Pediatric, Inflammation, Leukotriene, Montelukast
Brief summary
Background: In recent years, the prevalence of both asthma and obesity has risen dramatically among children and adolescents in the United States. Given the concurrent rise in the two epidemics, there may be an underlying link. Obesity contributes to asthma severity and control, and may play a role in its underlying cause. Obesity is associated with a state of heightened inflammation that may lead to an increase asthma symptoms and severity. Obese adult patients treated with montelukast, an anti-inflammatory agent, seemed to have better asthma control than those treated with other standard asthma medications. The use of montelukast in obese children and adolescents has not been specifically studied. Hypotheses and Specific Aims: The use of montelukast will improve asthma symptoms and objective markers of asthma to a greater degree in obese, as opposed to non-obese children and adolescents. The investigators would like to determine if the use of montelukast will improve objective asthma scores, pulmonary function, markers of inflammation and medication use to a greater degree in obese as opposed to non-obese children/adolescents. Potential Impact: Given the growing epidemic of obesity-associated asthma in the U.S., a tailored approach focused on obese asthmatic children may help reduce the burden of this disease, health care costs and potential long-term complications as these children enter adulthood. Furthermore, this study may help clarify the underlying mechanisms that link asthma and obesity. Although this proposal is focused on one medication, it provides an example of how certain medications may have differential efficacy in the obese asthmatic.
Interventions
DRUGPlacebo
Age-dependent dose, nightly, 24 weeks
DRUGMontelukast
Age-dependent dose, nightly, 24 weeks
Sponsors
Thrasher Research Fund
Merck Sharp & Dohme LLC
New York State Department of Health
Northwell Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* mild to moderate persistent asthma based on 2007 NIH Asthma Guidelines * age 7-17 years old
Exclusion criteria
* present smoking or smoking history * other significant pulmonary or cardiac condition * recent (within the past three months) use of montelukast * on allergen immunotherapy * on omalizumab * pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Control Test (ACT) Scores | 24 weeks | The ACT is a validated questionaire-based tool designed to assess asthma control. Scale range for 7-11 year olds is 0-27 and for 12 years and older 5-25, with lower scores indicating poorer asthma control for all ages. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Leptin Levels | 24 weeks | Leptin levels, measured through blood, mediate appetite and are elaborated by adipose tissue. Levels correlate positively with body fat percentage. In addition, leptin plays a role in producing an inflammatory state. Adiponectin, which is also secreted by adipose tissue, regulates metabolism, however its levels are inversely correlated with body fat percentage. |
| Urinary Leukotriene E4 (LTE4) Levels | 24 weeks | LTE4 levels, measured in the urine, reflect the degree of inflammation in the asthmatic airway. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. |
| Exhaled Nitric Oxide Measurement | 24 weeks | A non-invasive measure of eosinophilic airway inflammation. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. |
| Spirometric Measures | 24 weeks | Breathing maneuvers which help to measure obstruction of airways. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. |
| Urinary Creatinine (Cr) Levels | 24 weeks | Creatinine, measured in the urine, reflects how well the kidneys are working, and provide a standard to which one can compare other metabolites in the urine. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. |
| Urinary Creatinine (Cr) Levels/Leukotriene E4 (LTE4) Ratio | 24 weeks | The ratio of urinary LTE4 to Cr provides a standardization of the LTE4 level based on the patients weight and muscle mass, therefore normalizing it across the different subjects. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. |
| Beclomethasone Equivalents | 24 weeks | The total daily dose of inhaled corticosteroids in beclomethasone equivalents. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. |
Countries
United States
Participant flow
Recruitment details
Atopic asthmatics age seven and above seen in pulmonary and allergy clinics were approached over a 2.5 year period.
Pre-assignment details
Potential subjects underwent spirometry with bronchodilator administration if there was no previous documentation and allergy testing (skin/blood) to evaluate for environmental allergies.There was a four to six week run-in period where all participants were maintained on an inhaled corticosteroid before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Obese Atopic Asthmatics, Montelukast Montelukast: Age-dependent dose, nightly, 24 weeks | 7 |
| Normal-weight Atopic Asthmatics, Placebo Placebo: Age-dependent dose, nightly, 24 weeks | 5 |
| Normal Weight Atopic Asthmatics, Montelukast Montelukast: Age-dependent dose, nightly, 24 weeks | 5 |
| Obese Atopic Asthmatics, Placebo Placebo: Age-dependent dose, nightly, 24 weeks | 9 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 3 |
| Overall Study | Lost to Follow-up | 3 | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Normal Weight Atopic Asthmatics, Montelukast | Obese Atopic Asthmatics, Montelukast | Normal-weight Atopic Asthmatics, Placebo | Obese Atopic Asthmatics, Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 10 years | 10 years | 9 years | 9 years | 10 years |
| BMI | 18.28 kg/m^2 | 30.76 kg/m^2 | 17.83 kg/m^2 | 24.20 kg/m^2 | 22.09 kg/m^2 |
| Height (cm) | 143.00 cm | 153.30 cm | 134.4 cm | 144.90 cm | 143.95 cm |
| Race/Ethnicity, Customized African-American | 1 participants | 1 participants | 0 participants | 3 participants | 5 participants |
| Race/Ethnicity, Customized Caucasian | 2 participants | 2 participants | 3 participants | 2 participants | 9 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 1 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Other | 1 participants | 4 participants | 1 participants | 2 participants | 8 participants |
| Region of Enrollment United States | 5 participants | 7 participants | 5 participants | 9 participants | 26 participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 2 Participants | 3 Participants | 12 Participants |
| Weight (kg) | 37.00 kg | 72.3 kg | 32.66 kg | 52.00 kg | 48.50 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 7 | 0 / 5 | 0 / 5 | 3 / 9 |
| serious Total, serious adverse events | 0 / 7 | 0 / 5 | 0 / 5 | 0 / 9 |
Outcome results
Primary
Asthma Control Test (ACT) Scores
The ACT is a validated questionaire-based tool designed to assess asthma control. Scale range for 7-11 year olds is 0-27 and for 12 years and older 5-25, with lower scores indicating poorer asthma control for all ages. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overweight/Obese Atopic Asthmatics, Montelukast | Asthma Control Test (ACT) Scores | 25.00 units on a scale |
| Normal-weight Atopic Asthmatics, Placebo | Asthma Control Test (ACT) Scores | 20.5 units on a scale |
| Normal Weight Atopic Asthmatics, Montelukast | Asthma Control Test (ACT) Scores | 24.00 units on a scale |
| Overweight/Obese Atopic Asthmatics, Placebo | Asthma Control Test (ACT) Scores | 15.75 units on a scale |
Secondary
Beclomethasone Equivalents
The total daily dose of inhaled corticosteroids in beclomethasone equivalents. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overweight/Obese Atopic Asthmatics, Montelukast | Beclomethasone Equivalents | 680 micrograms |
| Normal-weight Atopic Asthmatics, Placebo | Beclomethasone Equivalents | 740 micrograms |
| Normal Weight Atopic Asthmatics, Montelukast | Beclomethasone Equivalents | 580 micrograms |
| Overweight/Obese Atopic Asthmatics, Placebo | Beclomethasone Equivalents | 1210.00 micrograms |
Secondary
Exhaled Nitric Oxide Measurement
A non-invasive measure of eosinophilic airway inflammation. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overweight/Obese Atopic Asthmatics, Montelukast | Exhaled Nitric Oxide Measurement | 14.33 ppb |
| Normal-weight Atopic Asthmatics, Placebo | Exhaled Nitric Oxide Measurement | 27.25 ppb |
| Normal Weight Atopic Asthmatics, Montelukast | Exhaled Nitric Oxide Measurement | 25.75 ppb |
| Overweight/Obese Atopic Asthmatics, Placebo | Exhaled Nitric Oxide Measurement | 39.5 ppb |
Secondary
Serum Leptin Levels
Leptin levels, measured through blood, mediate appetite and are elaborated by adipose tissue. Levels correlate positively with body fat percentage. In addition, leptin plays a role in producing an inflammatory state. Adiponectin, which is also secreted by adipose tissue, regulates metabolism, however its levels are inversely correlated with body fat percentage.
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overweight/Obese Atopic Asthmatics, Montelukast | Serum Leptin Levels | Serum leptin level | 44.35 ng/mL |
| Overweight/Obese Atopic Asthmatics, Montelukast | Serum Leptin Levels | serum adiponectin | 10.27 ng/mL |
| Normal-weight Atopic Asthmatics, Placebo | Serum Leptin Levels | serum adiponectin | 11.35 ng/mL |
| Normal-weight Atopic Asthmatics, Placebo | Serum Leptin Levels | Serum leptin level | 4.13 ng/mL |
| Normal Weight Atopic Asthmatics, Montelukast | Serum Leptin Levels | Serum leptin level | 10.90 ng/mL |
| Normal Weight Atopic Asthmatics, Montelukast | Serum Leptin Levels | serum adiponectin | 13.08 ng/mL |
| Overweight/Obese Atopic Asthmatics, Placebo | Serum Leptin Levels | Serum leptin level | 34.88 ng/mL |
| Overweight/Obese Atopic Asthmatics, Placebo | Serum Leptin Levels | serum adiponectin | 9.52 ng/mL |
Secondary
Spirometric Measures
Breathing maneuvers which help to measure obstruction of airways. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis.
Time frame: 24 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Overweight/Obese Atopic Asthmatics, Montelukast | Spirometric Measures | FEF 25-75% | 87.62 percent predicted |
| Overweight/Obese Atopic Asthmatics, Montelukast | Spirometric Measures | FVC% | 91.01 percent predicted |
| Overweight/Obese Atopic Asthmatics, Montelukast | Spirometric Measures | PEF (peak expiratory flow)% | 100.19 percent predicted |
| Overweight/Obese Atopic Asthmatics, Montelukast | Spirometric Measures | FEV1/FVC | 83.13 percent predicted |
| Overweight/Obese Atopic Asthmatics, Montelukast | Spirometric Measures | FEV1% | 83.37 percent predicted |
| Normal-weight Atopic Asthmatics, Placebo | Spirometric Measures | FEV1/FVC | 89.35 percent predicted |
| Normal-weight Atopic Asthmatics, Placebo | Spirometric Measures | FEF 25-75% | 78.57 percent predicted |
| Normal-weight Atopic Asthmatics, Placebo | Spirometric Measures | PEF (peak expiratory flow)% | 74.44 percent predicted |
| Normal-weight Atopic Asthmatics, Placebo | Spirometric Measures | FVC% | 88.87 percent predicted |
| Normal-weight Atopic Asthmatics, Placebo | Spirometric Measures | FEV1% | 85.31 percent predicted |
| Normal Weight Atopic Asthmatics, Montelukast | Spirometric Measures | FEV1/FVC | 88.25 percent predicted |
| Normal Weight Atopic Asthmatics, Montelukast | Spirometric Measures | FEV1% | 97.87 percent predicted |
| Normal Weight Atopic Asthmatics, Montelukast | Spirometric Measures | FVC% | 101.68 percent predicted |
| Normal Weight Atopic Asthmatics, Montelukast | Spirometric Measures | FEF 25-75% | 103.77 percent predicted |
| Normal Weight Atopic Asthmatics, Montelukast | Spirometric Measures | PEF (peak expiratory flow)% | 108.09 percent predicted |
| Overweight/Obese Atopic Asthmatics, Placebo | Spirometric Measures | FEF 25-75% | 66.99 percent predicted |
| Overweight/Obese Atopic Asthmatics, Placebo | Spirometric Measures | FVC% | 76.21 percent predicted |
| Overweight/Obese Atopic Asthmatics, Placebo | Spirometric Measures | FEV1% | 71.79 percent predicted |
| Overweight/Obese Atopic Asthmatics, Placebo | Spirometric Measures | FEV1/FVC | 80.42 percent predicted |
| Overweight/Obese Atopic Asthmatics, Placebo | Spirometric Measures | PEF (peak expiratory flow)% | 92.79 percent predicted |
Secondary
Urinary Creatinine (Cr) Levels
Creatinine, measured in the urine, reflects how well the kidneys are working, and provide a standard to which one can compare other metabolites in the urine. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis.
Time frame: 24 weeks
Population: One subject in the normal weight atopic asthmatic group who was receiving placebo did not provide a urine sample at 24 weeks.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overweight/Obese Atopic Asthmatics, Montelukast | Urinary Creatinine (Cr) Levels | 1.7 mg/mL |
| Normal-weight Atopic Asthmatics, Placebo | Urinary Creatinine (Cr) Levels | 1.69 mg/mL |
| Normal Weight Atopic Asthmatics, Montelukast | Urinary Creatinine (Cr) Levels | 1.77 mg/mL |
| Overweight/Obese Atopic Asthmatics, Placebo | Urinary Creatinine (Cr) Levels | 2.77 mg/mL |
Secondary
Urinary Creatinine (Cr) Levels/Leukotriene E4 (LTE4) Ratio
The ratio of urinary LTE4 to Cr provides a standardization of the LTE4 level based on the patients weight and muscle mass, therefore normalizing it across the different subjects. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis.
Time frame: 24 weeks
Population: One subject in the normal weight atopic asthmatic group who was receiving placebo did not provide a urine sample at 24 weeks.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overweight/Obese Atopic Asthmatics, Montelukast | Urinary Creatinine (Cr) Levels/Leukotriene E4 (LTE4) Ratio | 105.87 pg/mg |
| Normal-weight Atopic Asthmatics, Placebo | Urinary Creatinine (Cr) Levels/Leukotriene E4 (LTE4) Ratio | 99.61 pg/mg |
| Normal Weight Atopic Asthmatics, Montelukast | Urinary Creatinine (Cr) Levels/Leukotriene E4 (LTE4) Ratio | 159.84 pg/mg |
| Overweight/Obese Atopic Asthmatics, Placebo | Urinary Creatinine (Cr) Levels/Leukotriene E4 (LTE4) Ratio | 177.92 pg/mg |
Secondary
Urinary Leukotriene E4 (LTE4) Levels
LTE4 levels, measured in the urine, reflect the degree of inflammation in the asthmatic airway. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis.
Time frame: 24 weeks
Population: One subject in the normal weight atopic asthmatic group who was receiving placebo did not provide a urine sample at 24 weeks.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Overweight/Obese Atopic Asthmatics, Montelukast | Urinary Leukotriene E4 (LTE4) Levels | 171.50 pg/mL |
| Normal-weight Atopic Asthmatics, Placebo | Urinary Leukotriene E4 (LTE4) Levels | 195.67 pg/mL |
| Normal Weight Atopic Asthmatics, Montelukast | Urinary Leukotriene E4 (LTE4) Levels | 198.00 pg/mL |
| Overweight/Obese Atopic Asthmatics, Placebo | Urinary Leukotriene E4 (LTE4) Levels | 313.00 pg/mL |