Oral Nadolol for the Treatment of Adults With Mild Asthma

• Sponsor: Invion, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00670267
• Collaborator: University of Houston (Other), Sandler Program for Asthma Research (Other), Baylor College of Medicine (Other)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 29
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to confirm previous observations in asthmatics that chronic nadolol treatment reduces asthmatic airway hyper-responsiveness.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: nadolol	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Dose-Escalating, Study to Evaluate the Safety, Efficacy and Tolerability of Oral Nadolol for the Treatment of Adults With Mild Asthma
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Open Label treatment with oral Nadolol Dose escalation through 1.25mgs, 2.5mgs, 5.0mgs, 10mgs, 20mgs, and 40mgs of nadolol at 2 week intervals as tolerated.	Drug: nadolol; Nadolol, oral taken daily, doses will be escalated every two weeks over 13 weeks following a 2 week run-in.; Other Names: Corgard

Outcome Measures

Primary Outcome Measures

1. Mean Daily Dose at Study Termination Across Participants [Baseline to end of study (105 days)]

   The outcome measure describes the mean daily dose achieved by the subjects at study termination. This data includes one subject who terminated early, having reached 2.5mgs and subsequently reducing to 1.25mgs prior to dropping out.

2. Daily Dose at Study Termination Across Participants [Baseline to end of study (105 days)]

   The outcome measure describes the final daily dose achieved by the subjects in this study. The subjects described below who finished on less than the highest dose (i.e., 1.25, 5, and 10mgs) had all been down-titrated one dose (i.e., from 2.5, 10, and 20mgs) prior to completing the study on the dose reported.

Secondary Outcome Measures

1. Change in Airway Hyper-reactivity Compared to Baseline (Change in PC20 Doubling Dose by Methacholine Challenge) [Baseline to end of study (105 days)]

   Bronchoprovocation assessment was done by doubling doses of methacholine in accordance with the methodology recommended by the American Thoracic Society in the official policy statement adopted by the ATS Board of Directors, July 1999 (Guidelines for Methacholine and Exercise Challenge Testing-1999).

2. Percent Change in FEV1% Predicted From Baseline to End of Study [Baseline to end of study (105 days)]

3. Change in Asthma Control Questionnaire (ACQ) Score Compared to Baseline [Baseline to end of study (105 days)]

   In the E.F. Juniper Asthma Control Questionnaire, a lower number reflects better control of asthma symptoms. A positive change in ACQ score reflects a reduction in control compared to baseline; conversely, a negative change in ACQ score reflects an increase in control compared to baseline. The ACQ has 7 questions (the top scoring 5 symptoms, FEV1% pred. and daily rescue bronchodilator use). Patients are asked to recall how their asthma has been during the previous week and to respond to the symptom and bronchodilator use questions on a 7-point scale (0=no impairment, 6= maximum impairment). Clinic staff score the FEV1% predicted on a 7-point scale. The questions are equally weighted and the ACQ score is the mean of the 7 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

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

• PC20 FEV1 ≤4 mg/ml on methacholine challenge test.

• Blood Pressure ≥ 100/65mm Hg.

• Pulse rate ≥ 60 beats/min.

• No significant health issues.

• Non-smoker or X-smoker < 10 pack/year.

Exclusion Criteria:

• History of upper/lower respiratory tract infection or asthma exacerbation within 6 weeks of first baseline visit.

• Currently diagnosed with chronic obstructive pulmonary disease (COPD).

• Used any oral or inhaled corticosteroids within 4 weeks of the first baseline visit.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• Invion, Inc.
• University of Houston
• Sandler Program for Asthma Research
• Baylor College of Medicine

Investigators

• Principal Investigator: Nicola A Hanania, MD, University of Houston

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• ERS Publication: Response to salbutamol in patients with mild asthma treated with nadolol

Publications

• Hanania NA, Singh S, El-Wali R, Flashner M, Franklin AE, Garner WJ, Dickey BF, Parra S, Ruoss S, Shardonofsky F, O'Connor BJ, Page C, Bond RA. The safety and effects of the beta-blocker, nadolol, in mild asthma: an open-label pilot study. Pulm Pharmacol Ther. 2008;21(1):134-41. Epub 2007 Jul 17.
• Nguyen LP, Lin R, Parra S, Omoluabi O, Hanania NA, Tuvim MJ, Knoll BJ, Dickey BF, Bond RA. Beta2-adrenoceptor signaling is required for the development of an asthma phenotype in a murine model. Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2435-40. doi: 10.1073/pnas.0810902106. Epub 2009 Jan 26.

• Responsible Party: Invion, Inc.
• ClinicalTrials.gov Identifier: NCT00670267
• Other Study ID Numbers: SAND1002
• First Posted: May 1, 2008
• Last Update Posted: May 11, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Invion, Inc.: Asthma; hyperresponsiveness
• Additional relevant MeSH terms: Asthma; Nadolol

Study Results

Participant Flow

Arm/Group Title	Open Label Treatment With Oral Nadolol
Arm/Group Description	Dose escalation through 1.25mgs, 2.5mgs, 5.0mgs, 10mgs, 20mgs, and 40mgs of nadolol at 2 week intervals as tolerated.
Period Title: Overall Study
STARTED	10
COMPLETED	9
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Open Label
Arm/Group Description	nadolol: Nadolol, oral taken daily, doses will be escalated every two weeks over 13 weeks following a 2 week run-in.
Overall Participants	10
Age (Count of Participants)
<=18 years	1 10%
Between 18 and 65 years	9 90%
>=65 years	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	32.6
Sex: Female, Male (Count of Participants)
Female	8 80%
Male	2 20%
Region of Enrollment (participants) [Number]
United States	10 100%

Outcome Measures

1. Primary Outcome

Title	Mean Daily Dose at Study Termination Across Participants
Description	The outcome measure describes the mean daily dose achieved by the subjects at study termination. This data includes one subject who terminated early, having reached 2.5mgs and subsequently reducing to 1.25mgs prior to dropping out.
Time Frame	Baseline to end of study (105 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Treatment With Oral Nadolol
Arm/Group Description	Dose escalation through 1.25mgs, 2.5mgs, 5.0mgs, 10mgs, 20mgs, and 40mgs of nadolol at 2 week intervals as tolerated. nadolol: Nadolol, oral taken daily, doses will be escalated every two weeks over 13 weeks following a 2 week run-in.
Measure Participants	10
Mean (Standard Deviation) [mg]	29.6 (16.8)

2. Primary Outcome

Title	Daily Dose at Study Termination Across Participants
Description	The outcome measure describes the final daily dose achieved by the subjects in this study. The subjects described below who finished on less than the highest dose (i.e., 1.25, 5, and 10mgs) had all been down-titrated one dose (i.e., from 2.5, 10, and 20mgs) prior to completing the study on the dose reported.
Time Frame	Baseline to end of study (105 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Treatment With Oral Nadolol
Arm/Group Description	Dose escalation through 1.25mgs, 2.5mgs, 5.0mgs, 10mgs, 20mgs, and 40mgs of nadolol at 2 week intervals as tolerated.
Measure Participants	10
1.25mgs	1 10%
2.5mgs	0 0%
5.0mgs	1 10%
10.0mgs	1 10%
20mgs	0 0%
40mgs	7 70%

3. Secondary Outcome

Title	Change in Airway Hyper-reactivity Compared to Baseline (Change in PC20 Doubling Dose by Methacholine Challenge)
Description	Bronchoprovocation assessment was done by doubling doses of methacholine in accordance with the methodology recommended by the American Thoracic Society in the official policy statement adopted by the ATS Board of Directors, July 1999 (Guidelines for Methacholine and Exercise Challenge Testing-1999).
Time Frame	Baseline to end of study (105 days)

Outcome Measure Data

Analysis Population Description

Analysis excludes one early termination subject

Arm/Group Title	Open Label Treatment With Oral Nadolol
Arm/Group Description
Measure Participants	9
Mean (Standard Deviation) [mg/mL]	1.8 (1.3)

4. Secondary Outcome

Title	Percent Change in FEV1% Predicted From Baseline to End of Study
Time Frame	Baseline to end of study (105 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Treatment With Oral Nadolol
Arm/Group Description
Measure Participants	10
Mean (Standard Deviation) [percent change in FEV1% predicted]	-5.9 (9.7)

5. Secondary Outcome

Title	Change in Asthma Control Questionnaire (ACQ) Score Compared to Baseline
Description	In the E.F. Juniper Asthma Control Questionnaire, a lower number reflects better control of asthma symptoms. A positive change in ACQ score reflects a reduction in control compared to baseline; conversely, a negative change in ACQ score reflects an increase in control compared to baseline. The ACQ has 7 questions (the top scoring 5 symptoms, FEV1% pred. and daily rescue bronchodilator use). Patients are asked to recall how their asthma has been during the previous week and to respond to the symptom and bronchodilator use questions on a 7-point scale (0=no impairment, 6= maximum impairment). Clinic staff score the FEV1% predicted on a 7-point scale. The questions are equally weighted and the ACQ score is the mean of the 7 questions and therefore between 0 (totally controlled) and 6 (severely uncontrolled).
Time Frame	Baseline to end of study (105 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Open Label Treatment With Oral Nadolol
Arm/Group Description
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	0.3 (0.7)

Adverse Events

Arm/Group Title	Open Label
Arm/Group Description	nadolol: Nadolol, oral taken daily, doses will be escalated every two weeks over 13 weeks following a 2 week run-in.
All Cause Mortality
	Open Label
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Open Label
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Open Label
	Affected / at Risk (%)	# Events
Total	1/10 (10%)
Reproductive system and breast disorders
Reduced pulmonary function	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.