Role of Endorphins in Perception of Dyspnea With Resistive Loading in Chronic Obstructive Pulmonary Disease (COPD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00958919
First received: August 13, 2009
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

Endorphins are released in response to breathing difficulty and can modify the perception of breathlessness. In this randomized placebo-controlled trial, resistive breathing loads are used to provoke breathlessness in patients with chronic obstructive pulmonary disease. The hypothesis of the study is that intravenous (IV) administration of naloxone, a medication which blocks endorphin activity, will increase the perception of breathlessness experienced by patients while breathing through a resistance device, compared with IV administration of normal saline.


Condition Intervention
Chronic Obstructive Pulmonary Disease
Drug: naloxone
Drug: normal saline

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Role of Endorphins in the Perception of Dyspnea With Resistive Loading in Patients With COPD

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Intensity of Breathlessness [ Time Frame: At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7) ] [ Designated as safety issue: No ]

    The average of all ratings for the intensity of breathlessness at equivalent times for each subject during Resistive Load Breathing (RLB). For example, if 1 subject provided 6 ratings during 6 minutes of RLB with naloxone and 10 ratings during 10 minutes of RLB with normal saline, then ratings for intensity through 6 minutes were used for analysis for that patient. This approach was used for all subjects to yield a total of 154 ratings for naloxone and for normal saline.

    Subject rating of intensity of breathlessness was obtained at 1 minute intervals during RLB on a 100 mm Visual Analog Scale anchored at the bottom by "No Intensity" and at the top by "Greatest Intensity".


  • Unpleasantness of Breathlessness [ Time Frame: At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7) ] [ Designated as safety issue: No ]

    The average of all ratings for the unpleasantness of breathlessness at equivalent times for each subject during Resistive Load Breathing (RLB). For example, if 1 subject provided 6 ratings during 6 minutes of RLB with naloxone and 10 ratings during 10 minutes of RLB with normal saline, then ratings for intensity through 6 minutes were used for analysis for that patient. This approach was used for all subjects to yield a total of 154 ratings for naloxone and for normal saline.

    Subject rating of intensity of unpleasantness was obtained during RLB on a 100 mm Visual Analog Scale anchored at the bottom by "No Unpleasantness" and at the top by "Greatest Unpleasantness".



Secondary Outcome Measures:
  • Endurance Time [ Time Frame: Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7) ] [ Designated as safety issue: No ]
    Length of time that subjects were able to continue Resistive Load Breathing

  • Change in Level of B-endorphin Immunoreactivity During Naloxone Intervention [ Time Frame: Baseline and at the end of Resistance Load Breathing during either Period 1 (Day 3 or 4) or Period 2 (Day 5, 6 or 7) depending on randomization ] [ Designated as safety issue: No ]
    Change in serum levels of beta-endorphin immunoreactivity measured in pmol/L in subjects receiving Naloxone

  • Change in Level of B-endorphin Immunoreactivity During Saline Intervention [ Time Frame: Baseline and at the end of Resistance Load Breathing during either Period 1 (Day 3 or 4) or Period 2 (Day 5, 6 or 7) depending on randomization ] [ Designated as safety issue: No ]
    Change in serum levels of beta-endorphin immunoreactivity measured in pmol/L in subjects receiving Saline


Enrollment: 14
Study Start Date: August 2009
Study Completion Date: October 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: naloxone Drug: naloxone
10 mg naloxone in 25 ml total volume
Other Name: endorphin receptor antagonist
Placebo Comparator: normal saline Drug: normal saline
25 ml
Other Name: salt water

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  Eligibility

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patient 50 years of age or older;
  • A diagnosis of COPD defined by American Thoracic Society-European Respiratory Society criteria
  • Current or former smoker with a smoking history of greater than or equal to 10 pack-years;
  • A post-bronchodilator forced expiratory volume in one second (FEV1) greater than or equal to 30% predicted and less than or equal to 80% predicted; AND
  • A post-bronchodilator FEV1/forced vital capacity ratio less than 70%; and clinically stable COPD.

Exclusion Criteria:

  • Any patient who has a concomitant disease that might interfere with study procedures or evaluation;
  • Inability to perform resistive breathing maneuvers; OR
  • Any current use of a narcotic medication.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00958919

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0001
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Donald A Mahler, M.D. Dartmouth-Hitchcock Medical Center
  More Information

Publications:
Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00958919     History of Changes
Other Study ID Numbers: 21721
Study First Received: August 13, 2009
Results First Received: November 5, 2012
Last Updated: March 1, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dartmouth-Hitchcock Medical Center:
breathlessness intensity
breathlessness unpleasantness
endorphins
resistive breathing loads

Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases
Endorphins
Naloxone
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Narcotic Antagonists
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 19, 2014