Obesity and Asthma: Nutrigenetic Response to Omega-3 Fatty Acids

Study Overview
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Brief Summary
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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
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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.

Official Title
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Obesity & Asthma: Nutrigenetic Response to Omega-3 Fatty Acids

Conditions
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Asthma, Obesity

Intervention / Treatment
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* Dietary Supplement: omega-3 polyunsaturated fatty acids
* Drug: Omega-3 Fatty Acid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 25 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: omega-3 fatty acids<br>3 softgels (EPA, DHA) twice daily | Dietary Supplement: omega-3 polyunsaturated fatty acids<br>* ProEPA Xtra 1000mg softgels: 3 softgels twice daily<br>* Other names: ProEPA Xtra 1000mg softgels;|
| Placebo Comparator: control<br>Soybean oil: 3 matched softgel caps twice daily | Drug: Omega-3 Fatty Acid<br>* Soybean oil: 3(age 12-25) matched softgel caps twice daily<br>* Other names: Placebo Soybean oil 1000mg soft gels;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | baseline, 3 months, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| N3-to-n6 PUFA Ratio (Granulocytes) | Ratio of total omega-3 to total omega-6 polyunsaturated fatty acids from granulocytes in peripheral blood | Baseline, 3 and 6 months | 
| N3-to-n6 PUFA Ratio (Monocytes) | Ratio of total omega-3 to total omega-6 polyunsaturated fatty acids from monocytes in peripheral blood | Baseline, 3 months, 6 months | 
| 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. | Baseline, 3 months, 6 months | 
| Urinary Leukotriene-E4 | Leukotriene E4 obtained from urine was measured using liquid chromatography tandem mass spectrometry. | Baseline, 3 months, 6 months | 
| FEV1 | Forced expiratory volume in 1 second is a validated spirometry measure. | Baseline, 3 months, 6 months | 
| 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 | 6 months | 
| Phone Contacts | Phone contact was defined as an urgent or unscheduled phone contact to a medical provider for asthma | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Obesity, Pharmacogenetics, Nutrigenetics