Clinical trial NCT04108377: Phosphodiesterase 4 Inhibitor, Roflumilast, and the Effects of Inhibition in Severe Asthma
Official title: Phosphodiesterase 4 Inhibitor, Roflumilast, Improves Beta Agonist Responsiveness Compared to Placebo in Low T2 Asthma Patients.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Asthma
Keywords: Hyperinsulinemia
Phosphodiesterase 4 Inhibitor
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2019-09-30
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change in Beta 2 Agonist response from Baseline
timeFrame: 3 months
Secondary outcomes:
measure: Exhaled nitric oxide
timeFrame: 3 months
measure: Asthma Control Test score
timeFrame: 3 months
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis
state: California
Study officials:
affiliation: University of California, Davis
name: Nicholas Kenyon, MD
role: PRINCIPAL_INVESTIGATOR
References: