Treatment of Bronchial Asthma With Borage and Echium Seed Oils

• ClinicalTrials.gov Identifier: NCT00806442
• Recruitment Status: Completed
• First Posted: December 10, 2008
• Results First Posted: July 3, 2017
• Last Update Posted: July 3, 2017
• Sponsor: Brigham and Women's Hospital
• Collaborators: Wake Forest University Health Sciences; National Center for Complementary and Integrative Health (NCCIH)
• Information provided by (Responsible Party): Elliot Israel, MD, Brigham and Women's Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Bronchial Asthma	Drug: Borage Seed Oil and Echium Seed Oil; Dietary Supplement: Corn Oil	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Treatment of Bronchial Asthma With Borage and Echium Seed Oils
• Study Start Date: December 2008
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: August 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1: Borage Seed Oil and Echium Seed Oil; 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; 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.; Other Names: CROSSENTIAL GLA TG40; INCROMEGA V3
Placebo Comparator: 2: Placebo Comparator; Placebo comparator: 9 g/day corn oil	Dietary Supplement: Corn Oil; 9 g/day of corn oil

Outcome Measures

Primary Outcome Measures :

1. Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: 6 weeks ]
   Forced expiratory volume in 1 second (FEV1) in plant seed oil vs. placebo

Secondary Outcome Measures :

1. Positive FEV1 Percent Predicted Change Among C Allele Carriers and A Homozygotes [ Time Frame: 6 weeks on each treatment assignment ]
   Number of participants with positive change in FEV1 % predicted (>0%) among C allele carriers and A homozygotes in each arm
2. Peak Flow Rate (PEFR) [ Time Frame: 6 weeks ]
   Morning Peak Flow Rate in plant seed oil vs. placebo
3. Frequency of Rescue Use of Short Acting Beta-2 Agonists [ Time Frame: 6 weeks ]
   Average number of puffs of albuterol daily in plant seed oil vs. placebo
4. Day-time Symptoms of Bronchial Asthma [ Time Frame: 6 weeks ]

   Day-time symptom scores in plant seed oil vs. placebo. 0 = Absent: No symptoms

   1. = Mild: Symptom did not interfere with normal daily activity or sleep
   2. = Moderate: Symptom was sufficient to interfere with normal daily activity or sleep
   3. = 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.

5. Night-time Wakenings [ Time Frame: 6 weeks ]
   Average number of night-time wakenings in plant seed oil vs. placebo
6. Urinary Leukotriene Levels [ Time Frame: 6 weeks ]
   Urinary leukotriene levels in plant seed oil vs. placebo

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Massachusetts

Asthma Research Center, Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

Wake Forest University Health Sciences

National Center for Complementary and Integrative Health (NCCIH)

Investigators

• Principal Investigator: Elliot Israel, MD; Brigham and Women's Hospital

More Information

Additional Information:

Asthma Research Center, Brigham and Women's Hospital 

Publications:

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.

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.

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.

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Elliot Israel, MD, Principal Investigator, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00806442
• Other Study ID Numbers: 2008p001696; P50AT002782 ( U.S. NIH Grant/Contract )
• First Posted: December 10, 2008
• Results First Posted: July 3, 2017
• Last Update Posted: July 3, 2017
• Last Verified: June 2017

Keywords provided by Elliot Israel, MD, Brigham and Women's Hospital:

Asthma; Fatty acids; Leukotrienes; Diet

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Borage oil; Antirheumatic Agents