Trial of Roflumilast in Asthma Management (TRIM)

NCT ID: NCT03532490

Last Updated: 2022-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-03
• Study Completion Date: 2021-07-30

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.

Conditions

Asthma; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Roflumilast 500 mcg oral tablet

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.

Group Type: ACTIVE_COMPARATOR

Roflumilast 500 Mcg Oral Tablet

Intervention Type: DRUG

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 tablet

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.

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

The first two weeks the participant will take one tablet every other day. If well tolerated, participant will take one tablet every day.

Interventions

Roflumilast 500 Mcg Oral Tablet

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

Placebo oral capsule

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

Other Intervention Names

Daliresp

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Lung Association

OTHER

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne Dixon, MD

Role: PRINCIPAL_INVESTIGATOR

University of Vermont

Robert Wise, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins School of Medicine

Locations

University of Alabama Lung Health Center

Birmingham, Alabama, United States

University of Arizona

Tucson, Arizona, United States

University of Illinois at Chicago, Breathe Chicago Center

Chicago, Illinois, United States

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Mount Sinai Icahn School of Medicine

New York, New York, United States

Duke University

Durham, North Carolina, United States

University of Vermont

Colchester, Vermont, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36170654 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R34HL135361

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00156697

Identifier Type: -

Identifier Source: org_study_id