Efficacy and Safety of Beta-adrenoceptor Inverse Agonist, Nadolol, in Mild Asthma

Phase 2

• Conditions: Mild Persistent Asthma, Uncomplicated
• Interventions: Drug: Placebo; Drug: Nadolol

• Registration Number: NCT01804218
• Lead Sponsor: Invion, Inc.

Brief Summary

The purpose of this study is to test the hypothesis that 18-22 week treatment with the inverse agonist nadolol will improve airway hyperresponsiveness in patients with mild asthma, compared to placebo.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-03-01
• Study First Submitted QC: 2013-03-01
• Study First Posted: 2013-03-05
• Primary Completion: 2016-05
• Status Verified: 2016-08
• Last Update Submitted: 2016-08-05
• Last Update Posted: 2016-08-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

1. Males and females with physician-diagnosed asthma between the ages of 18- 60.

2. Pre-bronchodilator FEV1 80% or greater than the predicted value

3. Baseline PC20 (based on FEV1) ≤ 4 mg/ml on methacholine challenge test.

4. Asthma Control Questionnaire Score (ACQ) <1.25

5. Baseline blood pressure ≥ 110/65mm Hg

6. Baseline pulse rate ≥ 60 beats/min.

7. Never-smoker or former-smoker < 10 pack.year and has not smoked within 1 year.

8. Able to complete diary cards and comply with study procedures.

9. Females of childbearing age may participate only if they have a negative pregnancy test, are non-lactating, and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.

Exclusion Criteria

Subjects who meet ANY of the following criteria are not eligible for enrollment:

1. Inability or unwillingness of the participant to give written informed consent
2. History of upper/lower respiratory tract infection or asthma exacerbation requiring systemic steroids within 6 weeks of Visit 1
3. Use of rescue medication (e.g., albuterol) more than twice per week during the week preceding Visit 1 excluding the use of such medication as preventative prior to exercise.
4. History of hospitalization for asthma in the preceding year
5. History of intubation for asthma
6. Currently diagnosed with chronic obstructive pulmonary disease (COPD)
7. Currently taking any beta-blocker medication
8. History of adverse reaction or allergy to any beta-blocker medication
9. History of neurological, hepatic, renal, or other medical conditions that may interfere with the interpretation of data or the patient's participation in the study or may increase safety concerns
10. Current diabetes or hyperthyroidism
11. History of cardiovascular diseases including uncontrolled hypertension (BP >160/100), ischemic heart disease, congestive heart failure, valvular heart disease or cardiomyopathy
12. Known allergy or sensitivity to atropine or ipratropium bromide
13. Abnormal entry laboratory values at baseline except for the following tests, where values outside the normal limits will be acceptable as follows: Hct ≥ 30%, platelet count > 100,000, ALT and AST < 1.5 x upper normal limit
14. Known bleeding disorders, platelet count <100,000, PT or PTT > 1.5 x normal control (if participating in bronchoscopy sub-study)
15. Known allergy to lidocaine (if participating in bronchoscopy sub-study)
16. Documented or self-reported current history of alcoholism or drug abuse
17. Participation in another research trial within 30 days of starting this trial
18. Unwillingness or inability to comply with study procedures
19. Inability to swallow the study medication capsule
20. Use of any exclusion medication within the time period specified
21. Pregnant or nursing
22. Receiving allergen immunotherapy (desensitization injections)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
Active, nadolol	Nadolol	Active

Primary Outcome Measures

Name	Time	Method
The change in methacholine provocative concentration causing a 20% fall (PC20) based on forced expiratory volume in 1 second (FEV1) between baseline visit and final dose dispensing visit.	4 months

Trial Locations

Locations (3)

Washington University School of Medicine; 🇺🇸 St. Louis, Missouri, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States