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

Primary Purpose

Asthma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Roflumilast
Placebo
Sponsored by
University of California, Davis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma focused on measuring Hyperinsulinemia, Phosphodiesterase 4 Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts 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).

Sites / Locations

  • UC Davis

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Roflumilast

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
September 26, 2019
Last Updated
October 20, 2023
Sponsor
University of California, Davis
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1. Study Identification

Unique Protocol Identification Number
NCT04108377
Brief Title
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

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
Enrollment stopped secondary to completion of funding
Study Start Date
January 21, 2019 (Actual)
Primary Completion Date
December 11, 2022 (Actual)
Study Completion Date
August 15, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, Davis

4. Oversight

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

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
Hyperinsulinemia, Phosphodiesterase 4 Inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Roflumilast
Arm Type
Experimental
Arm Description
Roflumilast 500mcg by mouth, once daily, for 70 days (10 weeks).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo by mouth, once daily, for 70 days (10 weeks).
Intervention Type
Drug
Intervention Name(s)
Roflumilast
Other Intervention Name(s)
Daliresp
Intervention Description
Roflumilast capsule
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for Roflumilast
Intervention Description
Sugar pill manufactured to mimic look of Roflumilast capsule
Primary Outcome Measure Information:
Title
Change in Beta 2 Agonist response from Baseline
Description
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.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Exhaled nitric oxide
Description
Determine where exhaled nitric oxide is lower in Group 1 vs Group 2
Time Frame
3 months
Title
Asthma Control Test score
Description
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?
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas Kenyon, MD
Organizational Affiliation
University of California, Davis
Official's Role
Principal Investigator
Facility Information:
Facility Name
UC Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States

12. IPD Sharing Statement

Links:
URL
https://studypages.com/s/a-study-of-the-experimental-medicine-roflumilast-for-severe-asthma-936481/
Description
Learn more or sign up for the study here!

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

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