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Trial of Roflumilast in Asthma Management (TRIM) (TRIM)

Primary Purpose

Asthma, Obesity

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Roflumilast 500 Mcg Oral Tablet
Placebo oral capsule
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • > 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

Sites / Locations

  • University of Alabama Lung Health Center
  • University of Arizona
  • University of Illinois at Chicago, Breathe Chicago Center
  • Northwestern University Feinberg School of Medicine
  • Mount Sinai Icahn School of Medicine
  • Duke University
  • University of Vermont

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Roflumilast 500 mcg oral tablet

Placebo oral tablet

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in Weight
Weight change measured in kilograms (kg).
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.
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.
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
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
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.
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.

Full Information

First Posted
May 9, 2018
Last Updated
September 9, 2022
Sponsor
Johns Hopkins University
Collaborators
American Lung Association, National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT03532490
Brief Title
Trial of Roflumilast in Asthma Management (TRIM)
Acronym
TRIM
Official Title
Trial of Roflumilast in Asthma Management (TRIM)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
August 3, 2018 (Actual)
Primary Completion Date
July 30, 2021 (Actual)
Study Completion Date
July 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
American Lung Association, National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Roflumilast 500 mcg oral tablet
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo oral tablet
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Roflumilast 500 Mcg Oral Tablet
Other Intervention Name(s)
Daliresp
Intervention Description
The first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day.
Intervention Type
Drug
Intervention Name(s)
Placebo oral capsule
Intervention Description
The first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day.
Primary Outcome Measure Information:
Title
Change in Asthma Control Test Score
Description
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.
Time Frame
Baseline and 24 weeks
Secondary Outcome Measure Information:
Title
Change in Weight
Description
Weight change measured in kilograms (kg).
Time Frame
Baseline and 24 weeks
Title
Change in Asthma Symptom Utility Index (ASUI)
Description
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.
Time Frame
baseline and 24 weeks
Title
Change in Gastrointestinal Symptom Rating Scale (GSRS)
Description
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.
Time Frame
Baseline and 24 weeks
Title
Change in Generalized Anxiety Disease (GAD-7)
Description
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
Time Frame
baseline and 24 weeks
Title
Change in Marks Asthma Quality of Life Questionnaire
Description
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
Time Frame
baseline and 24 weeks
Title
Change in SF 36
Description
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.
Time Frame
baseline and 24 weeks
Title
Change in PHQ9
Description
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.
Time Frame
baseline and 24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 > 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Dixon, MD
Organizational Affiliation
University of Vermont
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robert Wise, MD
Organizational Affiliation
Johns Hopkins School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama Lung Health Center
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of Illinois at Chicago, Breathe Chicago Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60608
Country
United States
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Mount Sinai Icahn School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
University of Vermont
City
Colchester
State/Province
Vermont
ZIP/Postal Code
05446
Country
United States

12. IPD Sharing Statement

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Trial of Roflumilast in Asthma Management (TRIM)

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