Treatment of Bronchial Asthma With Borage and Echium Seed Oils

Study Overview
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Brief Summary
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The aim of this trial is to determine the efficacy of a combination of two botanicals oils, borage seed oil and echium seed oil, as a potential treatment for bronchial asthma.

Detailed Description
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Leukotrienes are important in the pathogenesis of inflammation, and leukotriene modifying drugs are now an established treatment for bronchial asthma and rhinitis. Drugs that inhibit the biosynthesis of leukotrienes are likely to be more effective than the currently available drugs that antagonize a single leukotriene receptor. Dietary supplementation with gamma linolenic acid (GLA) in borage seed oil provides effective inhibition of leukotriene generation but also increases circulating free arachidonic acid (AA), which has pro-inflammatory potential. The n-3 fatty acid, eicosapentaenoic acid (EPA), prevented the conversion of GLA to AA. However, EPA is extracted from fish oil, is not well-tolerated due to its taste, and at higher doses appeared to blunt the inhibition of leukotriene biosynthesis by GLA. Stearidonic acid (SDA) is a precursor of EPA that is extracted from Echium plantagineum; it is converted to EPA in humans and it does not have the organoleptic properties of EPA. We recently completed a dose-ranging study in which we determined the dose of SDA that is sufficient to inhibit the rise in circulating levels of arachidonic acid while maintaining effective inhibition of leukotriene generation. The goal of the present study is to test the efficacy of dietary supplementation with GLA and SDA (provided in borage seed oil and echium seed oil) in treating bronchial asthma.

Official Title
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Treatment of Bronchial Asthma With Borage and Echium Seed Oils

Conditions
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Bronchial Asthma

Intervention / Treatment
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* Drug: Borage Seed Oil and Echium Seed Oil
* Dietary Supplement: Corn Oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of bronchial asthma Male or female 18 years to 65 years of age FEV1 50 to 90% of predicted, or personal best. Improvement of >=12% FEV1 with bronchodilator Exclusion Criteria: Pregnant or nursing Smoking history of > 10 pack years or active smoking within the past year. Due to possible effects on leukotriene biosynthesis, use of the following asthma treatments within the preceding month will be exclusion criteria: leukotriene modifying drugs, theophylline oral steroids. dietary supplements with fatty acids or other products that may interfere with leukotriene generation. Treatment within the previous three months with omalizumab (monoclonal antibody directed against IgE) Subjects will not be permitted to take non-steroidal anti-inflammatory drugs in the week prior to any measurements of ex vivo leukotriene generation because of their effects on leukotriene biosynthesis via inhibition of prostaglandin generation. A history of aspirin-sensitive asthma Significant abnormalities in CBC, differential white cell count, renal function, and liver function, or urinalysis. Any serious co-morbid medical condition.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1: Borage Seed Oil and Echium Seed Oil<br>Borage/Echium plant seed oils: 2 g/day of borage seed oil and 7 g/day of echium seed oil to provide 1.6 g/day of GLA and 0.9 g/day of SDA. | Drug: Borage Seed Oil and Echium Seed Oil<br>* 2 g/day of borage seed oil and 7 g/day of echium seed oil to provide 1.6 g/day of GLA and 0.9 g/day of SDA.<br>* Other names: INCROMEGA V3;|
| Placebo Comparator: 2: Placebo Comparator<br>Placebo comparator: 9 g/day corn oil | Dietary Supplement: Corn Oil<br>* 9 g/day of corn oil<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) | Forced expiratory volume in 1 second (FEV1) in plant seed oil vs. placebo | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes | Number of participants with positive change in FEV1 % predicted (>0%) among C allele carriers and A homozygotes in each arm | 6 weeks on each treatment assignment | 
| Peak Flow Rate (PEFR) | Morning Peak Flow Rate in plant seed oil vs. placebo | 6 weeks | 
| Frequency of Rescue Use of Short Acting Beta-2 Agonists | Average number of puffs of albuterol daily in plant seed oil vs. placebo | 6 weeks | 
| Day-time Symptoms of Bronchial Asthma | Day-time symptom scores in plant seed oil vs. placebo. 0 = Absent: No symptoms = Mild: Symptom did not interfere with normal daily activity or sleep = Moderate: Symptom was sufficient to interfere with normal daily activity or sleep = Severe: Symptom was so severe as to prevent normal daily activity or sleep These numbers were used for 1. Shortness of breath 2. Chest tightness 3. Wheezing 4. Cough 5. Phlegm/Mucus. The total score is the sum of the 5 item scores, for a range of 0-15. A higher score represents more severe symptoms. Each participant's score is the average of varying numbers of diary cards. The treatment phase visits at 6 weeks consisted of 3 weeks of diary cards with a +/- 5 day window. The baseline visits had 2 weeks of diary cards with a +/- 5 day window. The treatment phase measures are adjusted for the baseline measures. | 6 weeks | 
| Night-time Wakenings | Average number of night-time wakenings in plant seed oil vs. placebo | 6 weeks | 
| Urinary Leukotriene Levels | Urinary leukotriene levels in plant seed oil vs. placebo | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Fatty acids, Leukotrienes, Diet