AsthmaPhase 4MAN05NCT02682862
Ultra-long Acting Bronchodilator Therapy in Smoking Asthmatics
A Phase 4 study testing olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg and olodaterol 2.5 mcg in people with Asthma, run by University of Dundee at 1 site in United Kingdom.
Trial summary
Single centre, open-label, random order, cross-over trial, recruited over a period of approximately 2 years. Sufficient participants enrolled to complete 16 adults. Withdrawn subjects may be replaced. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Asthma
- What is being tested?
- olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg and olodaterol 2.5 mcg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 11 Jul 2016to 22 May 2019
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female volunteers aged 18-65 years with persistent asthma and on inhaled corticosteroids (at least 400 micrograms beclomethasone dipropionate equivalent dose daily)
- Current smoker
- Forced Expiratory Volume in 1 second (FEV1) ≥ 60 % predicted
- Ability to give informed consent
- Agreement for their General Practitioner to be made aware of study participation and to receive feedback as relevant to the participant's well being
Who cannot join
- Other significant respiratory diseases, in the opinion of the investigator, such as COPD or bronchiectasis.
- An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement or 3 months if hospital admission was required
- Any clinically significant medical condition that may endanger the health or safety of the participant
- Participation in another drug trial within 30 days before the commencement of the study
- Pregnancy or lactation
- Unable to comply with the procedures of the protocol
- Unable or unwilling to consent
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Scottish Centre for Respiratory Research, University of Dundee, Ninewells Hospital and Medical School
Dundee, Scotland, DD1 9SY
About this study
Official title: Effects of Ultra-long Acting Bronchodilator Therapy Assessed by Impulse Oscillometry in Smoking Asthmatics Taking Inhaled Corticosteroids
Single centre, open-label, random order, cross-over trial, recruited over a period of approximately 2 years. Sufficient participants enrolled to complete 16 adults. Withdrawn subjects may be replaced.
This clinical trial will assess the effects of ultra-long acting bronchodilator therapy in smoking asthmatics taking inhaled corticosteroids. This will be via a pulmonary function test called impulse oscillometry.
Read the detailed description
Cigarette smoking in asthma is associated with poorer asthma control and a higher frequency of asthma attacks. Despite this, smoking cessation rates are very low due to the highly addictive nature of tobacco smoking. Asthma in smokers is particularly challenging to manage because it is resistant to the beneficial effects of inhaled corticosteroids, the main treatment for asthma.
Unfortunately, there is no guideline consensus regarding how to best manage asthmatics who smoke. Research studies in asthma tend to exclude smokers because of concerns about recruiting patients with chronic obstructive pulmonary disease (COPD). Hence, there is an unmet need for research studies in asthmatics who are unable to stop smoking.
In view of the above, we propose to assess the effects of two different types of bronchodilators (inhalers which help open up the airways), in asthmatics who continue to smoke.
Participants will receive both of the following drugs for 2-4 weeks in random order, with a 2-3 week washout period in between:
Olodaterol which is a new long-acting bronchodilator. Olodaterol combined with tiotropium (dual bronchodilators). We wish to compare these inhalers using a sensitive pulmonary function test called impulse oscillometry.
- Conditions
- Asthma
- Being tested
- olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg, olodaterol 2.5 mcg
- Keywords
- tiotropium, olodaterol, smoker, cigarette, bronchodilator
- Medical subject headings
- Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcgDrug
Also called Spiolto Respimat 2.5mcg/2.5mcg
Inhaler: 2.5 microgram tiotropium (as bromide monohydrate) and 2.5 microgram olodaterol (as hydrochloride) per puff. 2 puffs once daily
olodaterol 2.5 mcgDrug
Also called Striverdi Respimat 2.5mcg
Inhaler: 2.5 microgram Olodaterol (as hydrochloride) per puff. 2 puffs once daily
| Study group | Role | What they receive |
|---|---|---|
| Spiolto Respimat | Experimental | olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg 2 puffs OD (once daily) for 2-4 weeks. Participants then enter washout period and receive alternative treatment arm Receives: Drug: olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg |
| Striverdi Respimat | Active comparator | olodaterol 2.5mcg 2 puffs OD (once daily) for 2-4 weeks. Participants then enter washout period and receive alternative treatment arm Receives: Drug: olodaterol 2.5 mcg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Airway resistance at 5Hz (R5)
measured by Impulse oscillometry (IOS)
Measured: 2-4 weeks
Secondary outcomes (14)
RF
Impulse Oscillometry: Resonant Frequency
Measured: 2-4 weeks
X5
Impulse Oscillometry: Reactance at 5Hz
Measured: 2-4 weeks
AX
Impulse Oscillometry: Reactance Area
Measured: 2-4 weeks
R5-R20
Impulse Oscillometry: Resistance at 5Hz minus Resistance at 20Hz, equating to small airway resistance
Measured: 2-4 weeks
R20
Impulse Oscillometry: Resistance at 20Hz
Measured: 2-4 weeks
FEF25-75 pre and post challenge
Spirometry: Forced expiratory flow 25%-75% pre and post bronchial challenge (assessing change)
Measured: 2-4 weeks
FVC pre and post challenge
Spirometry: Forced vital capacity pre and post bronchial challenge (assessing change)
Measured: 2-4 weeks
FEV1 pre and post challenge
Spirometry: Forced expiratory volume in 1 second pre and post bronchial challenge (assessing change)
Measured: 2-4 weeks
Mannitol PD30
Provocation dose of mannitol causing 30% increase in R5
Measured: 2-4 weeks
Mannitol RDR
Response-Dose Ratio
Measured: 2-4 weeks
R5 at PD30
Airway Resistance at 5 Hertz at PD30
Measured: 2-4 weeks
Salbutamol recovery time following mannitol challenge
Measured: 2-4 weeks
Domiciliary PEF
Peak Expiratory Flow
Measured: 2-4 weeks
ACQ
Asthma Control Questionnaire
Measured: 2-4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2016 (estimated)
- Study start11 Jul 2016
- Primary completion22 May 2019
- Study completion22 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sunny Jabbal, Mb Chb, Principal investigator, University of DundeeBrian Lipworth, MD, Mb Chb, Principal investigator, University of Dundee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02682862
- Sponsor's protocol ID
- 2013RC06
- Other IDs
- 2014-005317-23, 2014
- Acronym
- MAN05
- Status last verified
- Jun 2019
- First submitted
- 4 Feb 2016
- Last updated
- 21 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Lipworth B, RuiWen Kuo C, Jabbal S, Chan R. Inhaled triple therapy and airway hyperresponsiveness in persistent asthma. Ann Allergy Asthma Immunol. 2021 May;126(5):597-598. doi: 10.1016/j.anai.2021.01.032. Epub 2021 Feb 3. No abstract available.
PubMed 33548471Jabbal S, Kuo CR, Lipworth B. Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics. Clin Exp Allergy. 2020 Oct;50(10):1140-1147. doi: 10.1111/cea.13702. Epub 2020 Jul 27.
PubMed 33180376
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Ultra-long Acting Bronchodilator Therapy Assessed by Impulse Oscillometry in Smoking Asthmatics Taking Inhaled Corticosteroids
- ClinicalTrials.gov ID
- NCT02682862
- Acronym / sponsor ID
- MAN05 / 2013RC06
- Conditions
- Asthma
- Keywords
- tiotropium, olodaterol, smoker, cigarette, bronchodilator
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Study start
- 11 Jul 2016 (actual)
- Primary completion
- 22 May 2019 (actual)
- Study completion
- 22 May 2019 (actual)
- First posted
- 17 Feb 2016 (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.
Single centre, open-label, random order, cross-over trial, recruited over a period of approximately 2 years. Sufficient participants enrolled to complete 16 adults. Withdrawn subjects may be replaced.
This clinical trial will assess the effects of ultra-long acting bronchodilator therapy in smoking asthmatics taking inhaled corticosteroids. This will be via a pulmonary function test called impulse oscillometry.
Detailed description
Cigarette smoking in asthma is associated with poorer asthma control and a higher frequency of asthma attacks. Despite this, smoking cessation rates are very low due to the highly addictive nature of tobacco smoking. Asthma in smokers is particularly challenging to manage because it is resistant to the beneficial effects of inhaled corticosteroids, the main treatment for asthma.
Unfortunately, there is no guideline consensus regarding how to best manage asthmatics who smoke. Research studies in asthma tend to exclude smokers because of concerns about recruiting patients with chronic obstructive pulmonary disease (COPD). Hence, there is an unmet need for research studies in asthmatics who are unable to stop smoking.
In view of the above, we propose to assess the effects of two different types of bronchodilators (inhalers which help open up the airways), in asthmatics who continue to smoke.
Participants will receive both of the following drugs for 2-4 weeks in random order, with a 2-3 week washout period in between:
Olodaterol which is a new long-acting bronchodilator. Olodaterol combined with tiotropium (dual bronchodilators). We wish to compare these inhalers using a sensitive pulmonary function test called impulse oscillometry.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spiolto Respimat | Experimental | Drug: olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcgolodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg 2 puffs OD (once daily) for 2-4 weeks. Participants then enter washout period and receive alternative treatment arm |
| Striverdi Respimat | Active comparator | Drug: olodaterol 2.5 mcgolodaterol 2.5mcg 2 puffs OD (once daily) for 2-4 weeks. Participants then enter washout period and receive alternative treatment arm |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female volunteers aged 18-65 years with persistent asthma and on inhaled corticosteroids (at least 400 micrograms beclomethasone dipropionate equivalent dose daily)
- Current smoker
- Forced Expiratory Volume in 1 second (FEV1) ≥ 60 % predicted
- Ability to give informed consent
- Agreement for their General Practitioner to be made aware of study participation and to receive feedback as relevant to the participant's well being
Key exclusion criteria (7 listed)
- Other significant respiratory diseases, in the opinion of the investigator, such as COPD or bronchiectasis.
- An asthma exacerbation or respiratory tract infection requiring systemic steroids and/or antibiotics within 1 month of the study commencement or 3 months if hospital admission was required
- Any clinically significant medical condition that may endanger the health or safety of the participant
- Participation in another drug trial within 30 days before the commencement of the study
- Pregnancy or lactation
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 |
|---|---|---|
| olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcgAlso: Spiolto Respimat 2.5mcg/2.5mcgInhaler: 2.5 microgram tiotropium (as bromide monohydrate) and 2.5 microgram olodaterol (as hydrochloride) per puff. 2 puffs once daily | Drug | Spiolto Respimat |
| olodaterol 2.5 mcgAlso: Striverdi Respimat 2.5mcgInhaler: 2.5 microgram Olodaterol (as hydrochloride) per puff. 2 puffs once daily | Drug | Striverdi Respimat |
Primary outcome
Airway resistance at 5Hz (R5)
Time frame: 2-4 weeks
measured by Impulse oscillometry (IOS)
14 secondary outcomes
RF
Time frame: 2-4 weeks
X5
Time frame: 2-4 weeks
AX
Time frame: 2-4 weeks
R5-R20
Time frame: 2-4 weeks
R20
Time frame: 2-4 weeks
FEF25-75 pre and post challenge
Time frame: 2-4 weeks
FVC pre and post challenge
Time frame: 2-4 weeks
FEV1 pre and post challenge
Time frame: 2-4 weeks
Mannitol PD30
Time frame: 2-4 weeks
Mannitol RDR
Time frame: 2-4 weeks
R5 at PD30
Time frame: 2-4 weeks
Salbutamol recovery time following mannitol challenge
Time frame: 2-4 weeks
Domiciliary PEF
Time frame: 2-4 weeks
ACQ
Time frame: 2-4 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 21 Jun 2019.
- Derived from this study: PubMed 33548471Lipworth B, RuiWen Kuo C, Jabbal S, Chan R. Inhaled triple therapy and airway hyperresponsiveness in persistent asthma. Ann Allergy Asthma Immunol. 2021 May;126(5):597-598. doi: 10.1016/j.anai.2021.01.032. Epub 2021 Feb 3. No abstract available.
- Derived from this study: PubMed 33180376Jabbal S, Kuo CR, Lipworth B. Randomized controlled trial of triple versus dual inhaler therapy on small airways in smoking asthmatics. Clin Exp Allergy. 2020 Oct;50(10):1140-1147. doi: 10.1111/cea.13702. Epub 2020 Jul 27.
- Individual participant dataSharing planned: No
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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.
Sunny Jabbal, Mb Chb principal investigator
University of Dundee
Brian Lipworth, MD, Mb Chb principal investigator
University of Dundee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing olodaterol hydrochloride 2.5mcg, tiotropium bromide 2.5mcg and olodaterol 2.5 mcg in people with Asthma, run by University of Dundee at 1 site in United Kingdom.
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 5 inclusion and 7 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 21 Jun 2019. 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 United Kingdom. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Airway resistance at 5Hz (R5) (time frame: 2-4 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 NCT02682862, which also lists 2 linked publications.
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 21 Jun 2019.