MedTrace Logo

Differentiating the Effects of Substance P and Beta-endorphin

NCT01854177 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2018-10-30

Study results available
· View outcomes & findings →

Summary

In previous studies we demonstrated that endogenous opioids (inhibitory neuropeptides) modulate the perception of breathing difficulty in patients with chronic obstructive pulmonary disease (COPD). Recently, we found that antagonism of substance P (an excitatory neuropeptide) with aprepitant did not affect the perception of breathing difficulty. However, after administration of aprepitant, blood levels of both substance P(+ 54 ± 39%) and beta-endorphin (+ 27 ± 17%) increased significantly. As these blood levels reflect cellular/tissue activity, we postulated that the concomitant release of excitatory (substance P) and inhibitory (beta-endorphin) neuropeptides had opposing effects (counterbalanced each other) on the perception of breathing difficulty.

The objective of the present study is to further examine the possible role of substance P on the perception of breathlessness. We propose to administer oral aprepitant and oral placebo in a randomized clinical trial in patients with COPD. However, four hours after patients take these medications, intravenous naloxone will be administered in order to block the effects of endogenous opioids (beta-endorphin) on opioid receptors. Five minutes later, patients will breathe thru a tube with fine wire mesh to provoke breathing difficulty, and then provide ratings of the intensity and unpleasantness of breathlessness every minute.

The two competing hypothesis of the study are:

1. if breathlessness ratings with aprepitant/naloxone = placebo/naloxone, then substance P has no effect on perception of breathing difficulty;
2. if breathlessness ratings with aprepitant/naloxone ≠ placebo/naloxone, then substance P has an effect on perception of breathing difficulty.

Conditions

Interventions

DRUG

Aprepitant

DRUG

Placebo

Sponsors & Collaborators

  • Dartmouth-Hitchcock Medical Center

    lead OTHER

Principal Investigators

  • Donald A Mahler, M.D. · Dartmouth-Hitchcock Medical Center

Study Design

Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Model
CROSSOVER

Eligibility

Min Age
50 Years
Max Age
90 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2013-07-31
Primary Completion
2013-11-30
Completion
2013-11-30

Countries

  • United States

Study Locations

More Related Trials

Entities

Drugs
Diseases

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT01854177 on ClinicalTrials.gov