AsthmaPhase 2TRIMNCT03532490
Trial of Roflumilast in Asthma Management (TRIM)
A Phase 2 study testing Roflumilast 500 Mcg Oral Tablet in people with Asthma and Obesity, run by Johns Hopkins University at 7 sites in United States.
Trial summary
There are currently no treatments to specifically target asthma in obese adults. This pilot study is being conducted to investigate how effective roflumilast is in treating asthma in participants that have a higher BMI. Roflumilast can induce weight loss, which may lead to improved asthma control. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- Roflumilast 500 Mcg Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 7 sitesUnited States
- Study dates
- 3 Aug 2018to 30 Jul 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Physician diagnosis of asthma on regular prescribed controller therapy for at least 3 months
- Previous (within five years) evidence of at least a 12% increase in forced expiratory volume at one second FEV1 after inhaling 2-4 puffs of albuterol or a positive methacholine challenge or patient reported history of improvement of asthma exacerbation after a course of systemic or inhaled corticosteroids
- Age: ≥18 years of age
- Obese: Body Mass Index (BMI) > 30 kg/m2
- Poorly controlled asthma: Asthma Control Test (ACT) Score < 20, or use of rescue inhaler, on an average of> 2 uses/week for preceding month, or nocturnal asthma awakening, on an average of 1 or more times / week in preceding month, or emergency department (ED)/hospital visit or prednisone course for asthma in past six months.
- Ability and willingness to provide informed consent
Who cannot join
- Participation in an investigational study within the past 4 weeks
- Physician diagnosis of chronic obstructive pulmonary disease
- Any condition that puts the participant at risk from weight loss as judged by the site physician
- Liver cirrhosis
- Major psychiatric disorders such as generalized anxiety disorder, major depressive disorder, history of suicidal ideation/ attempt, panic disorder, post-traumatic stress disorder, schizophrenia, schizoaffective, substance abuse or other disorders that in the opinion of the study physician that would affect study participation
- > 0 time use of illicit drugs in the past 12 months
Show all 17Show fewer
- > 0 time use of cannabis in the past 12 months
- Uncontrolled depression as defined by a score of 15 or greater on the depression questions of the Patient Health Questionnaire (PHQ-9)
- Suicidal ideation (a score of greater than 0 on Question 9 on the PHQ-9)
- Uncontrolled anxiety as defined by a score of 10 or greater on the anxiety questions of the Generalized Anxiety Disorder 7-item (GAD-7)
- Pregnancy/lactation
- Females of childbearing age who do not agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.
- Greater than 20 pack year smoking history, or smoking within the last 6 months.
- History of bariatric surgery
- Drugs metabolized by cytochrome P450 (rifampicin, phenobarbital, carbamazepine, phenytoin, erythromycin, ketoconazole, cimetidine, fluvoxamine, enoxacin, oral contraceptives containing ethinyl estradiol with gestodene).
- Currently on roflumilast or theophylline (patient may wash out of these medications for 4 weeks prior to visit 1)
- Intention to move out of area within the next 6 months
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Alabama Lung Health Center
Birmingham, Alabama, 35294
University of Illinois at Chicago, Breathe Chicago Center
Chicago, Illinois, 60608
Northwestern University Feinberg School of Medicine
Chicago, Illinois, 60611
University of Vermont
Colchester, Vermont, 05446
Duke University
Durham, North Carolina, 27705
Mount Sinai Icahn School of Medicine
New York, New York, 10029
University of Arizona
Tucson, Arizona, 85724
About this study
There are currently no treatments to specifically target asthma in obese adults. This pilot study is being conducted to investigate how effective roflumilast is in treating asthma in participants that have a higher BMI. Roflumilast can induce weight loss, which may lead to improved asthma control.
The primary objective of TRIM is to perform a pilot placebo-controlled trial of roflumilast for the treatment of poorly controlled obese asthmatics.
Read the detailed description
TRIM is a 24 week, randomized, double-masked, placebo controlled trial that will enroll 38 participants.
This study will be take place in seven centers of the American Lung Association- Airways Clinical Research Centers (ALA-ACRC). The centers include: Northwestern University Feinberg School of Medicine, Mount Sinai Icahn School of Medicine, Duke University, University of Arizona, the University of Vermont, The University of Alabama Lung Health Center, and University of Illinois Breathe Chicago Center. Johns Hopkins University will be the Data Coordinating Center (DCC) for the trial.
- Being tested
- Roflumilast 500 Mcg Oral Tablet, Placebo oral capsule
- Medical subject headings
- Asthma, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Roflumilast 500 Mcg Oral TabletDrug
Also called Daliresp
The first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day.
Placebo oral capsuleDrug
The first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day.
| Study group | Role | What they receive |
|---|---|---|
| Roflumilast 500 mcg oral tablet | Active comparator | 500 mcg roflumilast oral tablets will be taken every other day for the first two weeks. If participant tolerates the drug, the tablet will be taken once daily. Receives: Drug: Roflumilast 500 Mcg Oral Tablet |
| Placebo oral tablet | Placebo comparator | 500 mcg placebo oral tablets will be taken every other day for the first two weeks. If participant tolerates the drug, the tablet will be taken once daily. Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Asthma Control Test Score
The Asthma Control Test was designed to help participants describe their asthma and how it affects how they feel and what they are able to do. They choose a response based on their asthma within the last 4 weeks. Participants select how many times per week they experience different asthma symptoms and how often they had to use a rescue inhaler or nebulizer. There are 5 questions with 5 responses; 1 meaning their asthma is not well controlled or they had symptoms more frequently, through 5 meaning they feel their asthma is well controlled or they do not experience any symptoms.
The primary outcome is an unadjusted comparison of 24 week change in Asthma Control Test scores between the treatment groups.
Measured: Baseline and 24 weeks
Secondary outcomes (7)
Change in Weight
Weight change measured in kilograms (kg).
Measured: Baseline and 24 weeks
Change in Asthma Symptom Utility Index (ASUI)
A 10-item questionnaire, patient preference-based scale assessing frequency and severity of selected asthma-related symptoms and treatment side effects, for use in clinical trials and cost-effectiveness studies in asthma. Range is 0-1. Higher score is indicative of better health.
Measured: baseline and 24 weeks
Change in Gastrointestinal Symptom Rating Scale (GSRS)
It has 5 subscales (Reflux, Diarrhea, Constipation, Abdominal Pain, and Indigestion Syndrome). Subscale scores range from 1 to 7 and higher scores represent more discomfort and poor health.
Measured: Baseline and 24 weeks
Change in Generalized Anxiety Disease (GAD-7)
GAD-7 has 7 questions. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. The following cut-offs correlate with level of anxiety severity:
Score 0-4: Minimal Anxiety Score 5-9: Mild Anxiety Score 10-14: Moderate Anxiety Score greater than 15: Severe Anxiety
Measured: baseline and 24 weeks
Change in Marks Asthma Quality of Life Questionnaire
20 items with 2 week recall. Self-administered questionnaire intended for use with adults. Respondents are asked to describe how troubling particular items have been over the past four weeks. Covers both physical and emotional impact. Range 1-4. lower score is indicative of better health
Measured: baseline and 24 weeks
Change in SF 36
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Range 0-100. Higher score is indicative of better health.
Measured: baseline and 24 weeks
Change in PHQ9
The PHQ-9 (Patient Health Questionnaire-9) objectifies and assesses degree of depression severity via questionnaire. It has 9 questions. Range 0-27, lower score is indicate of better health.
Measured: baseline and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2018
- Study start3 Aug 2018
- Primary completion30 Jul 2021
- Study completion30 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- American Lung Association, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Anne Dixon, MD, Principal investigator, University of VermontRobert Wise, MD, Principal investigator, Johns Hopkins School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03532490
- Sponsor's protocol ID
- IRB00156697
- Other IDs
- R34HL135361
- Acronym
- TRIM
- Status last verified
- Sep 2022
- First submitted
- 9 May 2018
- Last updated
- 6 Oct 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Dixon AE, Que LG, Kalhan R, Dransfield MT, Rogers L, Gerald LB, Kraft M, Krishnan JA, Johnson O, Hazucha H, Roy G, Holbrook JT, Wise RA. Roflumilast May Increase Risk of Exacerbations When Used to Treat Poorly Controlled Asthma in People with Obesity. Ann Am Thorac Soc. 2023 Feb;20(2):206-214. doi: 10.1513/AnnalsATS.202204-368OC.
PubMed 36170654
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Roflumilast in Asthma Management (TRIM)
- ClinicalTrials.gov ID
- NCT03532490
- Acronym / sponsor ID
- TRIM / IRB00156697
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- American Lung Association, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 3 Aug 2018 (actual)
- Primary completion
- 30 Jul 2021 (actual)
- Study completion
- 30 Jul 2021 (actual)
- First posted
- 22 May 2018 (actual)
- Results
- Posted 6 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
There are currently no treatments to specifically target asthma in obese adults. This pilot study is being conducted to investigate how effective roflumilast is in treating asthma in participants that have a higher BMI. Roflumilast can induce weight loss, which may lead to improved asthma control.
The primary objective of TRIM is to perform a pilot placebo-controlled trial of roflumilast for the treatment of poorly controlled obese asthmatics.
Detailed description
TRIM is a 24 week, randomized, double-masked, placebo controlled trial that will enroll 38 participants.
This study will be take place in seven centers of the American Lung Association- Airways Clinical Research Centers (ALA-ACRC). The centers include: Northwestern University Feinberg School of Medicine, Mount Sinai Icahn School of Medicine, Duke University, University of Arizona, the University of Vermont, The University of Alabama Lung Health Center, and University of Illinois Breathe Chicago Center. Johns Hopkins University will be the Data Coordinating Center (DCC) for the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Roflumilast 500 mcg oral tablet | Active comparator | Drug: Roflumilast 500 Mcg Oral Tablet500 mcg roflumilast oral tablets will be taken every other day for the first two weeks. If participant tolerates the drug, the tablet will be taken once daily. |
| Placebo oral tablet | Placebo comparator | Drug: Placebo oral capsule500 mcg placebo oral tablets will be taken every other day for the first two weeks. If participant tolerates the drug, the tablet will be taken once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Physician diagnosis of asthma on regular prescribed controller therapy for at least 3 months
- Previous (within five years) evidence of at least a 12% increase in forced expiratory volume at one second FEV1 after inhaling 2-4 puffs of albuterol or a positive methacholine challenge or patient reported history of improvement of asthma exacerbation after a course of systemic or inhaled corticosteroids
- Age: ≥18 years of age
- Obese: Body Mass Index (BMI) > 30 kg/m2
- Poorly controlled asthma: Asthma Control Test (ACT) Score < 20, or use of rescue inhaler, on an average of> 2 uses/week for preceding month, or nocturnal asthma awakening, on an average of 1 or more times / week in preceding month, or emergency department (ED)/hospital visit or prednisone course for asthma in past six months.
Key exclusion criteria (17 listed)
- Participation in an investigational study within the past 4 weeks
- Physician diagnosis of chronic obstructive pulmonary disease
- Any condition that puts the participant at risk from weight loss as judged by the site physician
- Liver cirrhosis
- Major psychiatric disorders such as generalized anxiety disorder, major depressive disorder, history of suicidal ideation/ attempt, panic disorder, post-traumatic stress disorder, schizophrenia, schizoaffective, substance abuse or other disorders that in the opinion of the study physician that would affect study participation
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 |
|---|---|---|
| Roflumilast 500 Mcg Oral TabletAlso: DalirespThe first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day. | Drug | Roflumilast 500 mcg oral tablet |
| Placebo oral capsuleThe first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day. | Drug | Placebo oral tablet |
Primary outcome
Change in Asthma Control Test Score
Time frame: Baseline and 24 weeks
The Asthma Control Test was designed to help participants describe their asthma and how it affects how they feel and what they are able to do. They choose a response based on their asthma within the last 4 weeks. Participants select how many times per week they experience different asthma symptoms and how often they had to use a rescue inhaler or nebulizer. There are 5 questions with 5 responses; 1 meaning their asthma is not well controlled or they had symptoms more frequently, through 5 meaning they feel their asthma is well controlled or they do not experience any symptoms. The primary outcome is an unadjusted comparison of 24 week change in Asthma Control Test scores between the treatment groups.
7 secondary outcomes
Change in Weight
Time frame: Baseline and 24 weeks
Change in Asthma Symptom Utility Index (ASUI)
Time frame: baseline and 24 weeks
Change in Gastrointestinal Symptom Rating Scale (GSRS)
Time frame: Baseline and 24 weeks
Change in Generalized Anxiety Disease (GAD-7)
Time frame: baseline and 24 weeks
Change in Marks Asthma Quality of Life Questionnaire
Time frame: baseline and 24 weeks
Change in SF 36
Time frame: baseline and 24 weeks
Change in PHQ9
Time frame: baseline and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36170654Dixon AE, Que LG, Kalhan R, Dransfield MT, Rogers L, Gerald LB, Kraft M, Krishnan JA, Johnson O, Hazucha H, Roy G, Holbrook JT, Wise RA. Roflumilast May Increase Risk of Exacerbations When Used to Treat Poorly Controlled Asthma in People with Obesity. Ann Am Thorac Soc. 2023 Feb;20(2):206-214. doi: 10.1513/AnnalsATS.202204-368OC.
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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.
Anne Dixon, MD principal investigator
University of Vermont
Robert Wise, MD principal investigator
Johns Hopkins School of Medicine
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Roflumilast 500 Mcg Oral Tablet in people with Asthma and Obesity, run by Johns Hopkins University at 7 sites in United States.
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 6 inclusion and 17 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 6 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 6 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Asthma Control Test Score (time frame: Baseline and 24 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 NCT03532490, 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 6 Oct 2022.