Effect of Dietary Supplements With Fish Oil on Mannitol-induced Airway Sensitivity & Inflammation in Persons With Asthma

NCT00526357 | Completed Phase 2

• 2 other identifiers: R.P. #06-2750Health Canada File No. 120532
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

We wish to investigate the effects of 3 weeks of orally administered fish oil supplements on the airway sensitivity (provoking dose to cause a 15% fall in FEV1, PD15) to inhaled mannitol (AridolTM). Mannitol, an osmotic stimulus has been demonstrated as a useful model for exercise-induced asthma. We also wish to investigate if there is any associated improvement associated with selected markers of airway inflammation that can be measured in the sputum, blood, urine and exhaled breath condensate. Oral fish oil supplements have recently been demonstrated to be effective inhibitors of exercise-induced asthma, in association with an inhibition of markers of inflammation, over a 3 week treatment period. This finding has important implications in the treatment of asthma as this is a faster and more effective improvement than what is seen with inhaled corticosteroids on exercise-induced asthma. This observation requires validation and further investigation. We wish to study this in two patient groups; (a) steroid naïve asthmatics taking beta2 agonist when required and (b) asthmatics taking regular inhaled corticosteroids \< 1000 mcg/day.

Conditions

Asthma

Keywords

omega-3 fatty acids; asthma; airway hyperresponsiveness; inflammation

Outcome Measures

Primary Outcomes (1)

• The cumulative dose of mannitol to cause a 15% reduction in FEV1 (PD15).

  3 weeks

Secondary Outcomes (1)

• Change following treatment in resting levels of eicosanoid metabolites in blood, urine & exhaled breath condensate (EBC). Sputum counts of eosinophils and metachromatic cells and LTB4, IL-a and TNF-a in sputum supernatant.

  3 weeks

Study Arms (2)

A

OTHER

Of the 24 asthmatic subjects, 12 will be enrolled who are taking beta2 agonists alone to treat their asthma

Drug: omega-3 fatty acid

B

OTHER

Of the 24 asthmatic subjects, 12 will be enrolled who are taking beta2 agonists and inhaled steroids to treat their asthma

Drug: omega-3 fatty acid

Interventions

omega-3 fatty acid DRUG

Pharmaceutical grade fish oil administered daily in the form of 10 capsules (5 capsules b.i.d.) each containing 400mg of eicosapentaenoic acid (EPA) and 200mg docosahexanoic acid (DHA) which will equate to a daily dose of 4000 mg of EPA and 2000 mg or DHA. The matched placebo containing a 50/50 mix of soybean and corn oil will be supplied by the same manufacturer (Ocean Nutrition, Canada)

Also known as: Meg-3, Product No. 4020EE

A; B

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female (medically or surgically postmenopausal or practicing an accepted form of barrier or hormonal contraception) subjects age 18-55.
• Stable, mild atopic asthma with forced expiratory volume in one second (FEV1) greater than 70% of predicted for age and height, and not requiring any medical treatment other than short acting inhaled beta2-agonists as required or for those on steroids, taking \< 1000 mcg of inhaled corticosteroid per day.
• No recent or significant history of cigarette smoking (no smoking within six months prior to entry into the study; less than 10 pack-years cumulative history of cigarette smoking).
• Signed written informed consent to participate in the study; ability to return to the clinic for repeated visits.
• No history of asthma exacerbations or acute intercurrent respiratory illness (viral respiratory syndrome, bronchitis, pneumonia) for a four week period preceding entry into the screening phase of the study.
• Subjects who take inhales steroids regularly must demonstrate reproducibility to inhaled mannitol (PD15\<1.0 doubling doses) during a 2 week run-in period.
• A PD15 to the mannitol challenge \< 315mg

You may not qualify if:

• Significant gastrointestinal (including hepatic), hematological, cardiovascular, cerebrovascular, metabolic such as including type II diabetes or other body system disorder.
• Regular consumption of fish consisting more than 1 meal of fish per week or regular fish oil supplements during the trial and for at least 2 weeks prior to the first study visit.
• Subjects who have taken oral corticosteroids or a leukotriene receptor antagonist in 4 weeks prior to entry into the study.
• Psychosis, alcoholism, active substance abuse, or any personality disorder, which would make compliance with this protocol problematic.
• Pregnant or nursing females.
• Any other medical or social condition which, in the opinion of the investigator, could confound the interpretation of the data derived from this study.
• Subjects taking \>1000 mcg of inhaled steroids daily in those subjects taking inhaled steroids.
• Subjects requiring regular anti-histamines for allergies.
• Subjects who have allergy to fish or any other ingredient in the study products.
• Subjects using anti-coagulants (warfarin, heparin)
• Subjects who have surgery planned over the course of the trial.
• Subjects who use medications to lower LDL cholesterol levels
• Subjects using non-steroidal anti-inflammatory medications (e.g., aspirin, ibuprofen)

Sponsors & Collaborators

• Firestone Institute for Respiratory Health: lead
• McMaster University: collaborator

Study Sites (1)

Firestone Institute for Respiratory Health

Hamilton, Ontario, L8N 4A6, Canada

Location

Related Publications (1)

• Brannan JD, Bood J, Alkhabaz A, Balgoma D, Otis J, Delin I, Dahlen B, Wheelock CE, Nair P, Dahlen SE, O'Byrne PM. The effect of omega-3 fatty acids on bronchial hyperresponsiveness, sputum eosinophilia, and mast cell mediators in asthma. Chest. 2015 Feb;147(2):397-405. doi: 10.1378/chest.14-1214.

  PMID: 25321659 DERIVED

MeSH Terms

Conditions

Asthma; Respiratory Hypersensitivity; Inflammation

Interventions

Fatty Acids, Omega-3

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Study Officials

• Paul M O'Byrne, MD

  Firestone Institute for Respiratory Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Manager

Study Record Dates

• First Submitted: September 6, 2007
• First Posted: September 10, 2007
• Study Start: August 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: March 1, 2012
• Last Updated: March 16, 2012

Record last verified: 2012-03

Locations

CA (1)