Differentiating the Effects of Substance P and Beta-endorphin

Completed · Not applicable · Has a placebo group

Conditions studied: Chronic Obstructive Pulmonary Disease

In brief

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.

Key facts

Study ID

NCT01854177

Run by

Dartmouth-Hitchcock Medical Center

People needed

10

Starts

2013-07-01

Expected to finish

2013-11-01

Last updated by the study team

2018-10-30

Who can join

Age: 50 and older, up to 90. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• male or female patient 50 years of age or older
• a diagnosis of COPD; former smoker with a history of greater than or equal to 10 pack-years
• a clinical diagnosis of chronic bronchitis (productive cough on most days for a minimum of three months per year for at least two successive 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
• a post-bronchodilator FEV1/forced vital capacity (FVC) ratio less than 70%; and clinically stable COPD.

You may not qualify if…

• current smoker
• pregnant women
• current or previous (within the past two weeks) use or of a narcotic medication
• any patient who has a concomitant disease that might interfere with study procedures or evaluation including lactose intolerance
• use of a drug that may cause possible drug interaction with aprepitant [including cilostazol, dofetilide, ergot alkaloids, oral or non-oral contraceptives, progestins, ranolazine, reboxetine, warfarin, ziprasidone, anxiolytic medications, anti-depressive medications, cholesterol lowering drugs (e.g., atorvastatin, simvastatin), theophylline, antifungal antibiotics, and macrolide antibiotics]
• use of a contraindicated medication including astemizole, cisapride, pimozide, and terfenadine;
• use of angiotensin converting enzyme inhibitor

Where it is running

• Dartmouth-Hitchcock Medical Center — Lebanon, New Hampshire, United States

Full record on ClinicalTrials.gov

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