AsthmaPhase 2NCT00526357
Effect of Dietary Supplements With Fish Oil on Mannitol-induced Airway Sensitivity & Inflammation in Persons With Asthma
A Phase 2 study testing omega-3 fatty acid in people with Asthma, run by Firestone Institute for Respiratory Health at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Asthma
- What is being tested?
- omega-3 fatty acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2007to Mar 2012
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 13Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
Canada1 site
Firestone Institute for Respiratory Health
Hamilton, Ontario, L8N 4A6
About this study
Official title: The Effect of Dietary Supplementation With Encapsulated Fish Oil on Mannitol-induced Airway Sensitivity and Inflammation in Persons With Asthma
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.
Read the 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.
- Conditions
- Asthma
- Being tested
- omega-3 fatty acid
- Keywords
- omega-3 fatty acids, asthma, airway hyperresponsiveness, inflammation
- Medical subject headings
- Asthma, Respiratory Hypersensitivity, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
omega-3 fatty acidDrug
Also called Meg-3, Product No. 4020EE
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)
| Study group | Role | What they receive |
|---|---|---|
| A | Other | Of the 24 asthmatic subjects, 12 will be enrolled who are taking beta2 agonists alone to treat their asthma Receives: 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 Receives: Drug: omega-3 fatty acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
The cumulative dose of mannitol to cause a 15% reduction in FEV1 (PD15).
Measured: 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.
Measured: 3 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2007 (estimated)
- Study startAug 2007
- Primary completionFeb 2009
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Firestone Institute for Respiratory Health
- Sponsor type
- University, hospital or other
- Collaborators
- McMaster University
- Responsible party
- Principal investigator, Michael Quinn, Firestone Institute for Respiratory Health
- Investigators
- Paul M O'Byrne, MD, Principal investigator, Firestone Institute for Respiratory Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00526357
- Sponsor's protocol ID
- R.P. #06-2750
- Other IDs
- Health Canada File No. 120532
- Status last verified
- Mar 2012
- First submitted
- 6 Sep 2007
- Last updated
- 16 Mar 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 25321659
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Dietary Supplementation With Encapsulated Fish Oil on Mannitol-induced Airway Sensitivity and Inflammation in Persons With Asthma
- ClinicalTrials.gov ID
- NCT00526357
- Acronym / sponsor ID
- R.P. #06-2750
- Conditions
- Asthma
- Keywords
- omega-3 fatty acids, asthma, airway hyperresponsiveness, inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Firestone Institute for Respiratory HealthUniversity, hospital or other
- Collaborators
- McMaster University
- Study start
- Aug 2007
- Primary completion
- Feb 2009 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 10 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Other | Drug: omega-3 fatty acidOf the 24 asthmatic subjects, 12 will be enrolled who are taking beta2 agonists alone to treat their asthma |
| B | Other | Drug: omega-3 fatty acidOf the 24 asthmatic subjects, 12 will be enrolled who are taking beta2 agonists and inhaled steroids to treat their asthma |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| omega-3 fatty acidAlso: Meg-3, Product No. 4020EEPharmaceutical 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) | Drug | A, B |
Primary outcome
The cumulative dose of mannitol to cause a 15% reduction in FEV1 (PD15).
Time frame: 3 weeks
1 secondary outcome
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.
Time frame: 3 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2012.
- Derived from this study: PubMed 25321659Brannan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul M O'Byrne, MD principal investigator
Firestone Institute for Respiratory Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing omega-3 fatty acid in people with Asthma, run by Firestone Institute for Respiratory Health at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The cumulative dose of mannitol to cause a 15% reduction in FEV1 (PD15). (time frame: 3 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00526357, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2012.