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

NCT00958919 | Completed Results

• 1 other identifier: 21721
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

breathlessness intensity; breathlessness unpleasantness; endorphins; resistive breathing loads

Outcome Measures

Primary Outcomes (2)

• Intensity of Breathlessness

  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".

  At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)

• Unpleasantness of Breathlessness

  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".

  At 1 minute intervals during Resistive Load Breathing at Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)

Secondary Outcomes (3)

• Endurance Time

  Period 1 (Day 3 or 4) and Period 2 (Day 5, 6 or 7)

• Change in Level of B-endorphin Immunoreactivity During Naloxone Intervention

  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

• Change in Level of B-endorphin Immunoreactivity During Saline Intervention

  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

Study Arms (2)

naloxone

EXPERIMENTAL

Drug: naloxone

normal saline

PLACEBO COMPARATOR

Drug: normal saline

Interventions

naloxone DRUG

10 mg naloxone in 25 ml total volume

Also known as: endorphin receptor antagonist

naloxone

normal saline DRUG

25 ml

Also known as: salt water

normal saline

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756-0001, United States

Location

Related Publications (1)

• Gifford AH, Mahler DA, Waterman LA, Ward J, Kraemer WJ, Kupchak BR, Baird JC. Neuromodulatory effect of endogenous opioids on the intensity and unpleasantness of breathlessness during resistive load breathing in COPD. COPD. 2011 Jun;8(3):160-6. doi: 10.3109/15412555.2011.560132. Epub 2011 Apr 22.

  PMID: 21513438 RESULT

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Naloxone; Saline Solution; Fluoridation

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Preventive Dentistry; Dentistry; Public Health Dentistry; Environment and Public Health

Results Point of Contact

• Title: Donald A. Mahler, M.D.
• Organization: Dartmouth-Hitchcock

Donald.a.mahler@hitchcock.org

603 650-5533

Study Officials

• Donald A Mahler, M.D.

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2009
• First Posted: August 14, 2009
• Study Start: August 1, 2009
• Primary Completion: August 1, 2010
• Study Completion: October 1, 2010
• Last Updated: April 11, 2013
• Results First Posted: April 11, 2013

Record last verified: 2013-03

Locations

US (1)