Asthma, Obesity
Conditions
Keywords
Asthma, Obesity, Pharmacogenetics, Nutrigenetics
Brief summary
This project will assess the effectiveness of omega-3 fatty acid supplementation in controlling asthma symptoms among obese asthmatics, and will assess if a person's genes influence response to treatment (personalized medicine). This project may improve our ability to treat asthma and our understanding of the link between obesity and asthma.
Detailed description
Obesity increases the risk for asthma diagnosis in children and adults. With obesity on the rise, a better understanding of this association may become critically important to public health. We will determine the impact of fish oil-derived Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) on asthma control among obese asthmatics. These omega-3 fatty acids have been shown to: reduce inflammation important to asthma and improve asthma outcomes in an inconsistent manner across previous smaller studies - results that are consistent with a pharmacogenetic influence. There exists evidence that omega-3 fatty acid response displays a pharmacogenetic response related to ALOX5 genotype. Preliminary data suggests that obese individuals are at greater risk for possessing this same ALOX5 variant and thus obese asthmatics may be more responsive to fish oil. We will determine (in a sub-aim) if there exists an ALOX5 genotype-related response effect with fish oil. This will be the largest clinical trial of omega-3 fatty acid for the treatment of asthma, and the first applying pharmacogenetic/nutrigenetic analysis.
Interventions
DIETARY_SUPPLEMENTomega-3 polyunsaturated fatty acids
ProEPA Xtra 1000mg softgels: 3 softgels twice daily
DRUGOmega-3 Fatty Acid
Soybean oil: 3(age 12-25) matched softgel caps twice daily
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Office of Dietary Supplements (ODS)
Nemours Children's Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* age 12-25 * BMI \> 25 (age 18-25) or BMI%\>85th (age 12-17) (BMI Liberalized) * Physician diagnosis of persistent asthma * Lung function responsiveness by bronchodilator reversibility or bronchoprovocation testing
Exclusion criteria
* pregnancy * currently taking LTRA for asthma control * other serious chronic medical condition * bleeding diathesis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Asthma Control Questionnaire (Juniper) | baseline, 3 months, 6 months | The ACQ ranges from 0 to 6 (higher values indicate worse asthma control). A score greater than 1.25 in children is considered poor asthma control, and a change of 0.4 or greater is considered clinical meaningful. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| N3-to-n6 PUFA Ratio (Monocytes) | Baseline, 3 months, 6 months | Ratio of total omega-3 to total omega-6 polyunsaturated fatty acids from monocytes in peripheral blood |
| Asthma Control Test | Baseline, 3 months, 6 months | The asthma control test assesses patient reported symptoms from the prior month and has a range from 5 to 25 with a higher score suggesting better asthma control. |
| Urinary Leukotriene-E4 | Baseline, 3 months, 6 months | Leukotriene E4 obtained from urine was measured using liquid chromatography tandem mass spectrometry. |
| N3-to-n6 PUFA Ratio (Granulocytes) | Baseline, 3 and 6 months | Ratio of total omega-3 to total omega-6 polyunsaturated fatty acids from granulocytes in peripheral blood |
| Exacerbations | 6 months | Exacerbations of asthma were defined by the need for urgent medical care (emergency room or urgent care clinic) or systemic corticosteroids to avoid severe worsening of asthma determined by study physician or local provider |
| Phone Contacts | 6 months | Phone contact was defined as an urgent or unscheduled phone contact to a medical provider for asthma |
| FEV1 | Baseline, 3 months, 6 months | Forced expiratory volume in 1 second is a validated spirometry measure. |
Countries
United States
Participant flow
Pre-assignment details
30 were excluded due to medical history and 15 was lost to follow-up during run-in.
Participants by arm
| Arm | Count |
|---|---|
| Omega-3 Fatty Acids 3 softgels (EPA, DHA) twice daily
omega-3 polyunsaturated fatty acids: ProEPA Xtra 1000mg softgels: 3 softgels twice daily | 77 |
| Control Soybean oil: 3 matched softgel caps twice daily
Omega-3 Fatty Acid: Soybean oil: 3(age 12-25) matched softgel caps twice daily | 21 |
| Total | 98 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 9 | 4 |
Baseline characteristics
| Characteristic | Omega-3 Fatty Acids | Total | Control |
|---|---|---|---|
| Age, Continuous | 14.6 years STANDARD_DEVIATION 2.2 | 14.6 years STANDARD_DEVIATION 2.1 | 14.6 years STANDARD_DEVIATION 2.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 27 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 71 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 40 Participants | 50 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 2 Participants |
| Race (NIH/OMB) White | 30 Participants | 39 Participants | 9 Participants |
| Region of Enrollment United States | 77 participants | 98 participants | 21 participants |
| Sex: Female, Male Female | 40 Participants | 51 Participants | 11 Participants |
| Sex: Female, Male Male | 37 Participants | 47 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 21 |
| other Total, other adverse events | 58 / 77 | 15 / 21 |
| serious Total, serious adverse events | 3 / 77 | 0 / 21 |
Outcome results
Primary
Asthma Control Questionnaire (Juniper)
The ACQ ranges from 0 to 6 (higher values indicate worse asthma control). A score greater than 1.25 in children is considered poor asthma control, and a change of 0.4 or greater is considered clinical meaningful.
Time frame: baseline, 3 months, 6 months
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omega-3 Fatty Acids | Asthma Control Questionnaire (Juniper) | Baseline | 1.13 score on a scale |
| Omega-3 Fatty Acids | Asthma Control Questionnaire (Juniper) | Change at 3 months | -0.08 score on a scale |
| Omega-3 Fatty Acids | Asthma Control Questionnaire (Juniper) | Change at 6 months | -0.09 score on a scale |
| Control | Asthma Control Questionnaire (Juniper) | Baseline | 1.08 score on a scale |
| Control | Asthma Control Questionnaire (Juniper) | Change at 3 months | -0.09 score on a scale |
| Control | Asthma Control Questionnaire (Juniper) | Change at 6 months | -0.18 score on a scale |
p-value: 0.05ANCOVA
Secondary
Asthma Control Test
The asthma control test assesses patient reported symptoms from the prior month and has a range from 5 to 25 with a higher score suggesting better asthma control.
Time frame: Baseline, 3 months, 6 months
Population: missing data due to drop outs or staff error
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omega-3 Fatty Acids | Asthma Control Test | Baseline | 19.4 units on a scale |
| Omega-3 Fatty Acids | Asthma Control Test | 3 months | 19.5 units on a scale |
| Omega-3 Fatty Acids | Asthma Control Test | 6 months | 20.2 units on a scale |
| Control | Asthma Control Test | Baseline | 19.9 units on a scale |
| Control | Asthma Control Test | 3 months | 20.3 units on a scale |
| Control | Asthma Control Test | 6 months | 20.4 units on a scale |
Secondary
Exacerbations
Exacerbations of asthma were defined by the need for urgent medical care (emergency room or urgent care clinic) or systemic corticosteroids to avoid severe worsening of asthma determined by study physician or local provider
Time frame: 6 months
Population: all randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omega-3 Fatty Acids | Exacerbations | 17 exacerbations |
| Control | Exacerbations | 5 exacerbations |
Secondary
FEV1
Forced expiratory volume in 1 second is a validated spirometry measure.
Time frame: Baseline, 3 months, 6 months
Population: missing data due to participants lost to follow-up or not being able to provide valid spirometry
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omega-3 Fatty Acids | FEV1 | Baseline | 90.2 percent of predicted |
| Omega-3 Fatty Acids | FEV1 | 3 months | 91.6 percent of predicted |
| Omega-3 Fatty Acids | FEV1 | 6 months | 91.6 percent of predicted |
| Control | FEV1 | Baseline | 90.3 percent of predicted |
| Control | FEV1 | 3 months | 90.2 percent of predicted |
| Control | FEV1 | 6 months | 91.7 percent of predicted |
Secondary
N3-to-n6 PUFA Ratio (Granulocytes)
Ratio of total omega-3 to total omega-6 polyunsaturated fatty acids from granulocytes in peripheral blood
Time frame: Baseline, 3 and 6 months
Population: Blood was not successfully drawn in all children
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omega-3 Fatty Acids | N3-to-n6 PUFA Ratio (Granulocytes) | Baseline | 0.06 no units (ratio) |
| Omega-3 Fatty Acids | N3-to-n6 PUFA Ratio (Granulocytes) | 3 months | 0.19 no units (ratio) |
| Omega-3 Fatty Acids | N3-to-n6 PUFA Ratio (Granulocytes) | 6 months | 0.17 no units (ratio) |
| Control | N3-to-n6 PUFA Ratio (Granulocytes) | Baseline | 0.10 no units (ratio) |
| Control | N3-to-n6 PUFA Ratio (Granulocytes) | 3 months | 0.08 no units (ratio) |
| Control | N3-to-n6 PUFA Ratio (Granulocytes) | 6 months | 0.08 no units (ratio) |
Secondary
N3-to-n6 PUFA Ratio (Monocytes)
Ratio of total omega-3 to total omega-6 polyunsaturated fatty acids from monocytes in peripheral blood
Time frame: Baseline, 3 months, 6 months
Population: blood was not successfully drawn in all children
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omega-3 Fatty Acids | N3-to-n6 PUFA Ratio (Monocytes) | Baseline | 0.04 no units (ratio) |
| Omega-3 Fatty Acids | N3-to-n6 PUFA Ratio (Monocytes) | 3 months | 0.11 no units (ratio) |
| Omega-3 Fatty Acids | N3-to-n6 PUFA Ratio (Monocytes) | 6 months | 0.12 no units (ratio) |
| Control | N3-to-n6 PUFA Ratio (Monocytes) | Baseline | 0.08 no units (ratio) |
| Control | N3-to-n6 PUFA Ratio (Monocytes) | 3 months | 0.05 no units (ratio) |
| Control | N3-to-n6 PUFA Ratio (Monocytes) | 6 months | 0.07 no units (ratio) |
Secondary
Phone Contacts
Phone contact was defined as an urgent or unscheduled phone contact to a medical provider for asthma
Time frame: 6 months
Population: all randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Omega-3 Fatty Acids | Phone Contacts | 10 events |
| Control | Phone Contacts | 6 events |
Secondary
Urinary Leukotriene-E4
Leukotriene E4 obtained from urine was measured using liquid chromatography tandem mass spectrometry.
Time frame: Baseline, 3 months, 6 months
Population: missing data resulted from participants lost to follow up or not providing urine samples
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Omega-3 Fatty Acids | Urinary Leukotriene-E4 | 6 months | 80.6 pg/mg creatinine |
| Omega-3 Fatty Acids | Urinary Leukotriene-E4 | Baseline | 70.1 pg/mg creatinine |
| Omega-3 Fatty Acids | Urinary Leukotriene-E4 | 3 months | 78.5 pg/mg creatinine |
| Control | Urinary Leukotriene-E4 | 6 months | 66.5 pg/mg creatinine |
| Control | Urinary Leukotriene-E4 | Baseline | 84.0 pg/mg creatinine |
| Control | Urinary Leukotriene-E4 | 3 months | 61.3 pg/mg creatinine |