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

Phosphodiesterase 4 Inhibitor, Roflumilast, Improves Beta Agonist Responsiveness Compared to Placebo in Low T2 Asthma Patients.

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.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: Roflumilast; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95816
      • UC Davis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Roflumilast; Roflumilast 500mcg by mouth, once daily, for 70 days (10 weeks).	Drug: Roflumilast; Roflumilast capsule; Other Names: Daliresp
Placebo Comparator: Placebo; Placebo by mouth, once daily, for 70 days (10 weeks).	Drug: Placebo; Sugar pill manufactured to mimic look of Roflumilast capsule; Other Names: Placebo for Roflumilast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Beta 2 Agonist response from Baseline	Determine whether β2 receptor responsiveness is improved in response to albuterol in Group 1 (Roflumilast) patients compared to Group 2 (Placebo) patients at the study entry.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exhaled nitric oxide	Determine where exhaled nitric oxide is lower in Group 1 vs Group 2	3 months
Asthma Control Test score	The Asthma Control Test (TM © 2002 by QualityMetric) is a validated instrument to measure symptom control in asthma patients. There are 5 questions each with a score of 1-5 (25 total points). Poor asthma control is considered with a score less than 20 out of 25. Determine whether Asthma Control Test score is improved in Group 1 vs Group 2 Asthma Control TestTM; In the past 4 weeks, how much of the time did your asthma keep you from getting as much done at work, school or at home?; During the past 4 weeks, how often have you had shortness of breath?; During the past 4 weeks, how often did your asthma symptoms (wheezing, coughing, shortness of breath, chest tightness or pain) wake you up at night or earlier than usual in the morning?; In the past 4 weeks, how often have you used your rescue inhaler or nebulizer medication (such as albuterol)?; How would you rate your asthma control during the past 4 weeks?	3 months

Collaborators and Investigators

• Sponsor: University of California, Davis
• Investigators: Principal Investigator: Nicholas Kenyon, MD, University of California, Davis

Publications and helpful links

Helpful Links

• Learn more or sign up for the study here!

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2019
• Primary Completion (Actual): December 11, 2022
• Study Completion (Actual): August 15, 2023

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: September 26, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 20, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Hyperinsulinemia; Phosphodiesterase 4 Inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 1406843

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes