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

Primary Purpose

Asthma

Status

Completed

Phase

Phase 2

Locations

Canada

Study Type

Interventional

Intervention

omega-3 fatty acid

About this trial

This is an interventional treatment trial for Asthma focused on measuring omega-3 fatty acids, asthma, airway hyperresponsiveness, inflammation

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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)

Sites / Locations

Firestone Institute for Respiratory Health

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT00526357

First Posted

September 6, 2007

Last Updated

March 15, 2012

Sponsor

Firestone Institute for Respiratory Health

Collaborators

McMaster University

1. Study Identification

Unique Protocol Identification Number

NCT00526357

Brief Title

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

Official Title

The Effect of Dietary Supplementation With Encapsulated Fish Oil on Mannitol-induced Airway Sensitivity and Inflammation in Persons With Asthma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2012

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

February 2009 (Actual)

Study Completion Date

March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Firestone Institute for Respiratory Health

Collaborators

McMaster University

4. Oversight

Data Monitoring Committee

5. Study Description

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.

Detailed Description

Asthma is a chronic inflammatory disorder of the airways characterized by recurrent episodes of dyspnea, wheeze and chest tightness and is associated with variable airway obstruction. Exercise-induced bronchoconstriction (EIB) is a feature specific to asthma. Exercise testing protocols have been developed to identify the presence of asthma as well as to assess asthma therapy. Airway narrowing following exercise in persons with asthma is thought to result from dry air hyperpnoea-induced dehydration of the airway surface, leading to the release of mediators from inflammatory cells residing in the airway. Regular treatment with inhaled corticosteroids inhibits the airway response to exercise by decreasing the number of inflammatory cells and thus the source of bronchoconstricting mediators. Therefore, a decrease in the source of mediator may be the reason for this eventual inhibition of the airway response to exercise. It has recently been demonstrated that fish oil supplementation in capsule form, taken daily over three weeks, provides significant protection against EIB. This protection appears to be of equal or greater efficacy than inhaled corticosteroids treatment over a similar period. This may have positive implications in the treatment of asthma as inhaled corticosteroids are known to have some unwanted side effects. Fish oil supplementation in the high doses given in previous studies have not demonstrated any side effects and may lead to an alternative treatment, or a decrease in the dose of inhaled steroids required in the treatment of asthma. A new bronchial provocation test using inhaled mannitol, derived from the mechanism of EIB, has been recently developed and is now registered in Australia and the European Union. Mannitol causes airway narrowing in a similar manner to exercise in persons with asthma and is effective in identifying responsiveness to inhaled corticosteroids. We wish to use inhaled mannitol as a model for EIB in an effort to further investigate the use of fish oil supplementation in the treatment of asthma. Our hypothesis is that daily orally administered encapsulated fish oil will attenuate the airway response to mannitol over a 3-week treatment period. We also wish to measure associated markers of inflammation in the blood, urine, sputum and exhaled condensate as well as monitor clinical outcomes such as symptoms and daily beta2 agonist use.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Other

Arm Description

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

Arm Title

Arm Type

Other

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

omega-3 fatty acid

Other Intervention Name(s)

Meg-3, Product No. 4020EE

Intervention Description

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)

Primary Outcome Measure Information:

Title

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

Time Frame

3 weeks

Secondary Outcome Measure Information:

Title

Time Frame

3 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Paul M O'Byrne, MD

Organizational Affiliation

Firestone Institute for Respiratory Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Firestone Institute for Respiratory Health

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8N 4A6

Country

Canada

12. IPD Sharing Statement

Citations:

PubMed Identifier

25321659

Citation

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.

Results Reference

derived

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

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