Trial of Roflumilast in Asthma Management (TRIM)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Trial of Roflumilast in Asthma Management (TRIM)

Conditions
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Asthma, Obesity

Intervention / Treatment
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* Drug: Roflumilast 500 Mcg Oral Tablet
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Roflumilast 500 mcg oral tablet<br>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. | Drug: Roflumilast 500 Mcg Oral Tablet<br>* The first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day.<br>* Other names: Daliresp;|
| Placebo Comparator: Placebo oral tablet<br>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. | Drug: Placebo oral capsule<br>* The first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Weight | Weight change measured in kilograms (kg). | 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. | 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. | 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 | 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 | 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. | 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. | baseline and 24 weeks |