Trial of Roflumilast in Asthma Management (TRIM)

NCT03532490 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB00156697R34HL135361
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 7

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.

Conditions

Asthma; Obesity

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change in Weight

  Baseline and 24 weeks

• Change in Asthma Symptom Utility Index (ASUI)

  baseline and 24 weeks

• Change in Gastrointestinal Symptom Rating Scale (GSRS)

  Baseline and 24 weeks

• Change in Generalized Anxiety Disease (GAD-7)

  baseline and 24 weeks

• Change in Marks Asthma Quality of Life Questionnaire

  baseline and 24 weeks

Study Arms (2)

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.

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.

Drug: Placebo oral capsule

Interventions

Roflumilast 500 Mcg Oral Tablet DRUG

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

Also known as: Daliresp

Roflumilast 500 mcg oral tablet

Placebo oral capsule 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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Johns Hopkins University: lead
• American Lung Association: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (7)

University of Alabama Lung Health Center

Birmingham, Alabama, 35294, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Illinois at Chicago, Breathe Chicago Center

Chicago, Illinois, 60608, United States

Location

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Mount Sinai Icahn School of Medicine

New York, New York, 10029, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

University of Vermont

Colchester, Vermont, 05446, United States

Location

Related Publications (1)

• 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.

  PMID: 36170654 DERIVED

MeSH Terms

Conditions

Asthma; Obesity

Interventions

Roflumilast; Tablets

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Gem Roy
• Organization: Johns Hopkins University

groy2@jhu.edu

4432875796

Study Officials

• Anne Dixon, MD

  University of Vermont

  PRINCIPAL INVESTIGATOR

• Robert Wise, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: May 22, 2018
• Study Start: August 3, 2018
• Primary Completion: July 30, 2021
• Study Completion: July 30, 2021
• Last Updated: October 6, 2022
• Results First Posted: October 6, 2022

Record last verified: 2022-09

Locations

US (7)