Fish Oil to Prevent Asthma Exacerbations in Patients With ALOX5 Polymorphisms

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Nicholas Kenyon, University of California, Davis
ClinicalTrials.gov Identifier:
NCT00621829
First received: February 12, 2008
Last updated: October 11, 2011
Last verified: October 2011
  Purpose

This is a clinical study that is designed to study the effects of the supplemental intake of enriched omega-3 polyunsaturated fatty acids (fish oil) in patients with moderate to severe asthma. Some asthmatics produce a large amount of inflammatory leukotriene proteins—proteins that contribute to wheezing and inflammation in the airway. Inhibiting the detrimental effects of leukotrienes is a key goal of controller therapy in severe asthmatics. Some asthmatic patients appear to have specific mutations of the arachidonate 5-lipoxygenase (ALOX5) gene, one gene that regulates the production of the inflammatory leukotrienes. Omega-3 fatty acids can interfere with the arachidonic acid pathway and decrease the production of leukotrienes, and this may benefit moderate and severe asthma patients. Our hypothesis is that omega-3 fatty acid supplements, added on to a patient's asthma medication regimen, can decrease the number of minor asthma exacerbations compared to patients who do not receive the supplement. Furthermore, we believe that asthma patients with specific ALOX5 gene mutations will benefit most. We will enroll 30 asthma subjects to take part in this trial. They will undergo genotyping of the ALOX5 gene and be treated with omega3-fatty acids (fish oil) and placebo over a nine month period. We expect that this strategy will allow us to discover which moderate and severe asthma patients will benefit most from supplements of omega-3 fatty acids. Treatment of chronic diseases, such as asthma, is a key mission of the Center of Health and Nutrition Research.


Condition Intervention
Asthma
Dietary Supplement: EPA enriched fish oils

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Pilot Study of Supplemental Eicosapentanoic Acid (EPA)-Enriched Omega-3 Polyunsaturated Fatty Acids (n3-PUFA) in a Subset of Moderate to Severe Asthmatics With Polymorphisms of the Arachidonate 5-lipoxygenase (ALOX5) Gene

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

Primary Outcome Measures:
  • Asthma exacerbations [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: February 2008
Study Completion Date: October 2011
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
"High" susceptibility ALOX5 gene polymorphisms. Patients will be classified as having high susceptibility ALOX5 gene polymorphisms based on the number of repeats of the SP1 promoter.
Dietary Supplement: EPA enriched fish oils
Subjects will take the (EPA)-enriched omega-3 polyunsaturated fatty acids (n3-PUFA) supplements as a capsule (3-4 g of EPA/day) for 90 days, followed by an 8 week washout period, and then will take a Placebo capsule for 90 days.
Other Names:
  • The study agent, a single-ingredient preparation,
  • is a commercially prepared and marketed fish oil
  • concentrate produced by Ocean Nutrition Canada (ONC)
  • Limited (http://www.ocean-nutrition.com/). This supplement
  • and related products are sold under the MEG-3® brand.
Active Comparator: 2
"Low" susceptibility ALOX5 gene polymorphisms. "Low" susceptibility ALOX5 gene polymorphisms. Patients will be classified as having high susceptibility ALOX5 gene polymorphisms based on the number of repeats of the SP1 promoter.
Dietary Supplement: EPA enriched fish oils
Subjects will take a Placebo capsule for 90 days, followed by an 8 week washout period, and then will take the (EPA)-enriched omega-3 polyunsaturated fatty acids supplements as a capsule (3-4 g of EPA/day) for 90 days.
Other Names:
  • omega 3 fatty acids
  • fish oil
  • Eicosapentanoic acids

Detailed Description:

This study is a single-center, investigator-initiated, randomized, double-blind, placebo-controlled, cross-over trial. A total of 30 subjects will be recruited from the U.C. Davis Asthma Network (UCAN) clinics. Some of the research will be conducted at the USDA-WHNRC (Western Health Nutrition Research Center) here at U.C. Davis.

This clinical trial is designed to study the effects of supplemental intake of eicosapentanoic acid (EPA)-enriched omega-3 polyunsaturated fatty acids (n3-PUFA, fish oil) in a subset of moderate to severe asthmatics, who have a high susceptibility to increased leukotriene production due to a polymorphism in the promoter region of the arachidonate 5-lipoxygenase (ALOX5) gene.

EPA competes with AA and can decrease leukotriene production; thus our central hypothesis is that EPA-enriched n3-PUFA supplements will decrease the production of inflammatory leukotrienes and decrease the number of acute exacerbations of asthma in patients with moderate to severe asthma and that these benefits will be greater in subjects with the "high susceptibility" ALOX5 promoter variants. Our specific aims are to: 1) Determine the prevalence of the "high-susceptibility" ALOX5 pathway gene polymorphisms in a diverse cohort of moderate to severe adult asthmatics, 2) Perform a 32 week (12 wk treatment A - 8 wk washout - 12 wk treatment B), blinded, cross-over design clinical trial, during which we treat 15 "high susceptibility" and 15 "low susceptibility" ALOX5 gene polymorphism asthmatics with n-3 PUFA supplements and placebo, and 3) Determine the baseline level and treatment effect of n-3 PUFA supplements on leukotriene metabolite and inflammatory cytokine production in subjects with the 'high' and 'low' susceptibility genotypes. Patients will be recruited primarily from the UC Davis Asthma Network (UCAN).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Children and adults patients >18 years or older with moderate and severe asthma (as diagnosed by lung specialist physician), based on the NIH NAEPP 1997 guidelines, who do not have an acute exacerbation at the time of enrollment and are on the same asthma medications for at least 1 month

Exclusion Criteria:

  • Less than 18 years of age
  • Baseline FEV1 < 35% predicted
  • Known or suspected allergy to fish oil products
  • Pregnant women and nursing women
  • Current smokers or subjects with a 20 pack-year history of smoking
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621829

Locations
United States, California
Ucdmc/Vanchcs Ccrc
Mather, California, United States, 95655
Sponsors and Collaborators
University of California, Davis
Investigators
Study Director: Charles Stephensen, Ph.D. USDA, Staff Scientist
Principal Investigator: Nicholas Kenyon, MD University of California, Davis
  More Information

No publications provided

Responsible Party: Nicholas Kenyon, Associate Professor, University of California, Davis
ClinicalTrials.gov Identifier: NCT00621829     History of Changes
Other Study ID Numbers: CHNR07702
Study First Received: February 12, 2008
Last Updated: October 11, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014