Albuterol and Dynamic Hyperinflation in Idiopathic Pulmonary Arterial Hypertension

The purpose of this study is to determine if dynamic hyperinflation seen in patients with idiopathic pulmonary artery hypertension (iPAH) improves with albuterol therapy.

Study Overview

• Status: Withdrawn
• Conditions: Idiopathic Pulmonary Arterial Hypertension.
• Intervention / Treatment: Drug: Albuterol.; Drug: Normal saline placebo

Detailed Description

Only a few small studies have evaluated the relationship between iPAH, expiratory flow limitation, and exercise dyspnea. While not all patients with iPAH demonstrate airway involvement, those who demonstrate dynamic hyperinflation (DH), defined as a variable and temporary increase in end-expiratory lung volume, report increased dyspnea with exertion on maximal testing. There is a continued need for adjuvant therapy in iPAH, and bronchodilators have the potential to ameliorate dyspnea during exercise, which could lead to improved quality of life in this disabling condition. This study will investigate the presence of airway involvement in this population as measured by dynamic hyperinflation, and if there is any improvement in function with the use of inhaled albuterol.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSUHSC Interim Louisiana Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age or greater.
• Idiopathic Pulmonary Arterial Hypertension, or Familial Pulmonary Arterial Hypertension.
• Forced expiratory flow 75% (FEF75%) of ≤ 65% of predicted.

Exclusion Criteria:

• Clinical instability or change in medication therapy in preceding 3 months.
• Allergy or intolerance to inhaled albuterol.
• Body mass index > 30
• Active tobacco use, or > 10 pack-year smoking history.
• Lung disease other than pulmonary hypertension
• Forced expiratory volume in 1 second (FEV1) ≤ 80% of predicted.
• Pregnancy
• Inability to perform pulmonary function testing.
• Inability to perform cardiopulmonary exercise testing.
• Supplemental oxygen requirement.
• Inability to read and understand English.
• Historical 6-minute walk distance <150 meters

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Albuterol; 2.5 mg of albuterol inhaled via jet nebulizer 15 minutes prior to symptom-limited maximal CPET.	Drug: Albuterol.; 2.5 mg of albuterol inhaled via jet nebulizer 15 minutes prior to symptom-limited maximal CPET.
Placebo Comparator: Placebo; Normal saline placebo inhaled via jet nebulizer 15 minutes prior to symptom-limited maximal CPET.	Drug: Normal saline placebo; Placebo inhaled via jet nebulizer 15 minutes prior to symptom-limited maximal CPET.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
End-expiratory lung volume:total lung capacity (EELV/TLC) ratio at matched metabolic isowork.	Determined by measuring inspiratory capacity every 2 minutes during cardiopulmonary exercise test (CPET)	up to 3 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in peak oxygen consumption with albuterol	Measured at the end of CPET	Study days 2 and 3
Change in O2 pulse with albuterol.	Measured throughout CPET and compared at matched metabolic isotimes	Study days 2 and 3
Exercise time	Total ramped exercise time	Study days 2 and 3
Borg dyspnea score	Measured every 2 minutes throughout CPET	Days 2 and 3

Collaborators and Investigators

• Sponsor: American Medical Association Foundation
• Investigators: Principal Investigator: Matthew Lammi, MD, Louisiana State University Health Sciences Center in New Orleans

Publications and helpful links

General Publications

• Meyer FJ, Ewert R, Hoeper MM, Olschewski H, Behr J, Winkler J, Wilkens H, Breuer C, Kubler W, Borst MM; German PPH Study Group. Peripheral airway obstruction in primary pulmonary hypertension. Thorax. 2002 Jun;57(6):473-6. doi: 10.1136/thorax.57.6.473.
• Fernandez-Bonetti P, Lupi-Herrera E, Martinez-Guerra ML, Barrios R, Seoane M, Sandoval J. Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary). Chest. 1983 May;83(5):732-8. doi: 10.1378/chest.83.5.732.
• Laveneziana P, Garcia G, Joureau B, Nicolas-Jilwan F, Brahimi T, Laviolette L, Sitbon O, Simonneau G, Humbert M, Similowski T. Dynamic respiratory mechanics and exertional dyspnoea in pulmonary arterial hypertension. Eur Respir J. 2013 Mar;41(3):578-87. doi: 10.1183/09031936.00223611. Epub 2012 Jul 12.
• Spiekerkoetter E, Fabel H, Hoeper MM. Effects of inhaled salbutamol in primary pulmonary hypertension. Eur Respir J. 2002 Sep;20(3):524-8. doi: 10.1183/09031936.02.02572001.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Anticipated): July 1, 2016
• Study Completion (Anticipated): October 1, 2016

Study Registration Dates

• First Submitted: April 7, 2014
• First Submitted That Met QC Criteria: April 8, 2014
• First Posted (Estimate): April 9, 2014

Study Record Updates

• Last Update Posted (Estimate): December 30, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Albuterol
• Other Study ID Numbers: IRB8603