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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04108377
• Other study ID #: 1406843
• Status: Terminated
• Phase: Phase 1
• Start date: January 21, 2019
• Est. completion date: August 15, 2023

Study information

• Verified date: May 2023
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: August 15, 2023
• Est. primary completion date: December 11, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Roflumilast
Roflumilast capsule
• Placebo
Sugar pill manufactured to mimic look of Roflumilast capsule

Locations

Country	Name	City	State
United States	UC Davis	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Beta 2 Agonist response from Baseline	Determine whether ß2 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	Exhaled nitric oxide	Determine where exhaled nitric oxide is lower in Group 1 vs Group 2	3 months
Secondary	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

External Links

•   Learn more or sign up for the study here!