Clinical trial NCT00806442: Treatment of Bronchial Asthma With Borage and Echium Seed Oils
Official title: Treatment of Bronchial Asthma With Borage and Echium Seed Oils
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Bronchial Asthma
Keywords: Asthma
Fatty acids
Leukotrienes
Diet
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Wake Forest University Health Sciences
name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2008-12-10
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 6 weeks
Secondary outcomes:
measure: Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes
timeFrame: 6 weeks on each treatment assignment
measure: Peak Flow Rate (PEFR)
timeFrame: 6 weeks
measure: Frequency of Rescue Use of Short Acting Beta-2 Agonists
timeFrame: 6 weeks
measure: Day-time Symptoms of Bronchial Asthma
timeFrame: 6 weeks
measure: Night-time Wakenings
timeFrame: 6 weeks
measure: Urinary Leukotriene Levels
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Asthma Research Center, Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Elliot Israel, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: James MJ, Ursin VM, Cleland LG. Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids. Am J Clin Nutr. 2003 May;77(5):1140-5. doi: 10.1093/ajcn/77.5.1140.
citation: Chilton-Lopez, Surette ME, Swan DD, Fonteh AN, Johnson MM, Chilton FH. Metabolism of gammalinolenic acid in human neutrophils. J Immunol. 1996 Apr 15;156(8):2941-7.
citation: Johnson MM, Swan DD, Surette ME, Stegner J, Chilton T, Fonteh AN, Chilton FH. Dietary supplementation with gamma-linolenic acid alters fatty acid content and eicosanoid production in healthy humans. J Nutr. 1997 Aug;127(8):1435-44. doi: 10.1093/jn/127.8.1435.
citation: Barham JB, Edens MB, Fonteh AN, Johnson MM, Easter L, Chilton FH. Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets prevents serum arachidonic acid accumulation in humans. J Nutr. 2000 Aug;130(8):1925-31. doi: 10.1093/jn/130.8.1925.
citation: Surette ME, Koumenis IL, Edens MB, Tramposch KM, Chilton FH. Inhibition of leukotriene synthesis, pharmacokinetics, and tolerability of a novel dietary fatty acid formulation in healthy adult subjects. Clin Ther. 2003 Mar;25(3):948-71. doi: 10.1016/s0149-2918(03)80116-9.
citation: Surette ME, Koumenis IL, Edens MB, Tramposch KM, Clayton B, Bowton D, Chilton FH. Inhibition of leukotriene biosynthesis by a novel dietary fatty acid formulation in patients with atopic asthma: a randomized, placebo-controlled, parallel-group, prospective trial. Clin Ther. 2003 Mar;25(3):972-9. doi: 10.1016/s0149-2918(03)80117-0.
citation: Kazani S, Arm JP, Boyce J, Chhay H, Dutile S, Wechsler ME, Govindarajulu U, Ivester P, Ainsworth HC, Sergeant S, Chilton FH, Israel E. LTC4 synthase polymorphism modifies efficacy of botanical seed oil combination in asthma. Springerplus. 2014 Nov 6;3:661. doi: 10.1186/2193-1801-3-661. eCollection 2014.