Trial of Roflumilast in Asthma Management (TRIM)

TRIM is a 24 week, randomized, double-masked, placebo controlled trial that will enroll 38
participants.

This study will be take place in five 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, and the University of Vermont. Johns Hopkins University will be the Data
Coordinating Center (DCC) for the trial.

Inclusion Criteria:

- Physician diagnosis of asthma on regular prescribed controller therapy for at least 3
months

- Current or previous (within five years) evidence of at least a 12% increase in FEV1
after inhaling 2-4 puffs of albuterol or a positive methacholine challenge

- Age: ≥18 years of age

- Obese: BMI > 30 kg/m2

- Poorly controlled asthma: Asthma Control Test 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 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 10 or greater on the depression
questions of the 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