Phosphodiesterase 4 Inhibitor, Roflumilast, and the Effects of Inhibition in Severe Asthma

University of California (UC) Davis

Status and phase: Terminated; Phase 1

Conditions: Asthma

Treatments: Drug: Placebo; Drug: Roflumilast

Study type: Interventional

Funder types: Other

Identifiers

NCT04108377

1406843

Details and patient eligibility

About

This study evaluates the effects of roflumilast on restoring response β2 adrenoreceptor agonists in low T2, obese asthmatics. One group of participants will receive roflumilast for 3 months, while the other will receive a placebo.

Full description

T2 low asthma is common in obese asthmatics. New evidence suggests that hyperinsulinemia and insulin resistance, both common in obesity, are associated with an increased risk of concurrent asthma.

Targeting Phosphodiesterase 4 inhibitors (PDE4) allows for examination of a mechanism potentially linking obesity and asthma as well as identification of readily available and safe options to treat hyperinsulinemic, overweight asthmatics.

It is hypothesized that obesity and hyperinsulinemia contribute to asthma by impairing β2 adrenoreceptor function and that this can be rescued the PDE4 inhibitor, roflumilast.

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Have a physician diagnosis of asthma.
• Require treatment with moderate to high-dose >2500mcg/day of fluticasone or equivalent, or use of oral steroids

Also two of the following:

• Requirement for additional daily treatment with other controller medication
• Daily Asthma symptoms
• Forced Expiratory Volume / Forced Vital Capacity (FEV1/FVC) < 70% and FEV1< 80% predicted
• ≥1 urgent care visits/year
• ≥3 oral steroid bursts/year
• Near-fatal asthma event.
• Exhaled Nitric oxide (FeNO)<30 ppb
• Peripheral blood eosinophil count < 300 (x10-6/ul)
• Obesity, BMI≥30

Exclusion criteria

• Less than 18 years of age
• baseline FEV1 <30% predicted
• pregnant or nursing women
• current smokers or subject with >20 pack year history
• any history of intolerance of, or reaction to, Roflumilast.
• Prisoners
• Patients with liver disease
• Subjects with Hepatic impairment (contraindicated in moderate-to-severe liver impairment: Child-Pugh Score Class B/C) for example.
• Patients with clinically significant psychiatric history (i.e., suicidality, etc.) and psychiatric illness
• Patients using strong CYP 450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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5 participants in 2 patient groups, including a placebo group

Roflumilast

Experimental group

Description:

Roflumilast 500mcg by mouth, once daily, for 70 days (10 weeks).

Treatment:

Drug: Roflumilast

Placebo

Placebo Comparator group

Description:

Placebo by mouth, once daily, for 70 days (10 weeks).

Treatment:

Drug: Placebo