Differentiating the Effects of Substance P and Beta-endorphin
Status:
Completed
Trial end date:
2013-11-01
Target enrollment:
Participant gender:
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.
Phase:
N/A
Details
Lead Sponsor:
Dartmouth-Hitchcock Medical Center
Treatments:
Adrenocorticotropic Hormone Aprepitant beta-Endorphin Endorphins Fosaprepitant Melanocyte-Stimulating Hormones Neurokinin A Substance P