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

• Sponsor: University of California, Davis (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04108377
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 49.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Roflumilast; Drug: Placebo	Phase 1

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Phosphodiesterase 4 Inhibitor, Roflumilast, Improves Beta Agonist Responsiveness Compared to Placebo in Low T2 Asthma Patients.
• Actual Study Start Date: Jan 21, 2019
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Mar 1, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Beta 2 Agonist response from Baseline [3 months]

   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.

Secondary Outcome Measures

1. Exhaled nitric oxide [3 months]

   Determine where exhaled nitric oxide is lower in Group 1 vs Group 2

2. Asthma Control Test score [3 months]

   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?

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC Davis	Sacramento	California	United States	95816

Sponsors and Collaborators

• University of California, Davis

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Learn more or sign up for the study here!

Publications

None provided.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT04108377
• Other Study ID Numbers: 1406843
• First Posted: Sep 30, 2019
• Last Update Posted: Feb 15, 2022
• Last Verified: Jan 1, 2022

• 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
• Keywords provided by University of California, Davis: Hyperinsulinemia; Phosphodiesterase 4 Inhibitor
• Additional relevant MeSH terms: Asthma

Study Results

No Results Posted as of Feb 15, 2022