Codeine on Pharyngeal and Esophageal Motility

Effect of Codeine on Pharyngeal and Esophageal Motility in Healthy Subjects: a Double-blind, Placebo-controlled, Randomized, Cross-over Study

Opioids act on opioid receptors located in the brain as well as in the gastrointestinal (GI) tract to induce changes in motility. A variety of studies have linked chronic opioid use with changes in intestinal and to a lesser extent esophageal motility. Less is known about acute administration effects on distal esophageal motility and LES and even less with respect to proximal esophagus, UES and pharynx. Codeine, an opioid receptor agonist, by acting both centrally as well as in the periphery may induce changes in parts of the GI tract implicated in deglutition. Therefore, to evaluate the hypothesis the researchers will study motility patterns in the pharynx, UES, proximal and distal esophagus and LES in 22 healthy volunteers receiving placebo or codeine (60 mg) in a double-blind randomized cross-over controlled fashion. Motility patterns will be studied using state-of-the-art criteria and analytic tools (Chicago 3.0, AIMPlot analysis).

Study Overview

• Status: Completed
• Conditions: Esophageal Motility Disorders
• Intervention / Treatment: Drug: Codeine Phosphate; Drug: Siripus simplex

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Leuven, Belgium, 3000
    • Jan Tack

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers aged between 18-60 years old
• Written informed consent

Exclusion Criteria:

• No chronic disease/medication
• No GI symptoms
• Not pregnant or breast-feeding
• No history of head/neck surgery
• Not allergic to codeine

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Codeine	Drug: Codeine Phosphate; 30 mL of codeine phosphate 10mg/5mL
Placebo Comparator: Siripus simplex	Drug: Siripus simplex; Sugar syrup

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in distal contractile integral	The difference in distal contractile integral between the codeine and placebo condition	1 week
Difference in integrated relaxation pressure	The difference in integrated relaxation pressure between the codeine and placebo condition	1 week
Difference in distal latency	The difference in distal latency between the codeine and placebo condition.	1 week
Difference in pressure flow	The difference in pressure flow between the codeine and placebo condition	1 week

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Geeraerts A, Geysen H, Ballet L, Hofmans C, Clevers E, Omari T, Manolakis AC, Mols R, Augustijns P, Vanuytsel T, Rommel N, Tack J, Pauwels A. Codeine induces increased resistance at the esophagogastric junction but has no effect on motility and bolus flow in the pharynx and upper esophageal sphincter in healthy volunteers: A randomized, double-blind, placebo-controlled, cross-over trial. Neurogastroenterol Motil. 2021 May;33(5):e14041. doi: 10.1111/nmo.14041. Epub 2020 Nov 24.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2017
• Primary Completion (Actual): December 14, 2018
• Study Completion (Actual): December 14, 2018

Study Registration Dates

• First Submitted: December 11, 2018
• First Submitted That Met QC Criteria: December 18, 2018
• First Posted (Actual): December 21, 2018

Study Record Updates

• Last Update Posted (Actual): December 24, 2018
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: codeine; Esophageal motility; Pharyngeal motility
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Deglutition Disorders; Esophageal Diseases; Esophageal Motility Disorders; Esophageal Spasm, Diffuse; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Codeine
• Other Study ID Numbers: S60496

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No