Esophageal Dysfunction Associated With Opioids: Clinical Response and Manometric Findings After Opioid Discontinuation

NCT06522633 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: HCB/2022/0458
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Opioid-induced esophageal dysfunction is characterized by altered motility of the esophageal body or impaired function of the esophageal sphincters secondary to chronic opioid use. The diagnosis of this condition is made through high-resolution manometry. Following the discontinuation of opioid treatment, most patients experience a clear symptomatic improvement. Hypothesis: Opioids induce alterations in esophageal motility and esophageal sphincter function that revert after discontinuation of treatment. Outcome: To demonstrate through high-resolution esophageal manometry that the manometric alterations described in patients with chronic opioid use are secondary to opioid consumption and disappear after discontinuing use. Methods: In a group of patients with chronic opioid use and diagnosed with a major esophageal motor disorder through high-resolution esophageal manometry, a new high-resolution manometry will be performed after discontinuing opioid treatment for at least 7 days to assess any changes compared to the previous manometry. The treating physician will be contacted to inform them about the manometry findings and to consider the possibility of discontinuing opioid treatment. Patients will be informed about the association between opioids and esophageal motor disorders and the benefits of discontinuing the medication to evaluate the resolution of symptoms and the observed disorder. To avoid complications such as withdrawal syndrome or exacerbation of pain due to the reduction of analgesic medication, an alternative medication protocol will be used according to the recommendations of the psychiatry team associated with functional digestive disorders. Relevance: This project will determine whether the manometric alterations are primary or secondary to opioid treatment. If it is confirmed that they are secondary to the treatment, opioid treatment can be replaced with another analgesic treatment, and esophageal symptoms will improve without the need for more aggressive therapies.

Conditions

Opioid Use

Keywords

Opioid-Associated Esophageal Dysfunction, dysphagia, esophageal motility

Outcome Measures

Primary Outcomes (1)

• Improvement in Esophageal Motility Demonstrate the improvement in esophageal motility in chronic opioid users after discontinuation of opioids.

  Assessment Tool: High-resolution esophageal manometry (HREM). Unit of Measure: Manometric parameters (e.g., integrated relaxation pressure (IRP) in mmHg). Prospective multicenter study in patients referred for non-obstructive dysphagia that were on chronic opioid treatment (\> 3 months). Patients were evaluated during the initial referral and then after 7 days without opioid use. In each visit, patients underwent a high-resolution esophageal manometry following the Chicago 4.0 protocol.

  Baseline (prior to opioid discontinuation) and 7 days post-opioid discontinuation

Secondary Outcomes (1)

• Improvement in Dysphagia Severity Demonstrate the improvement in dysphagia severity in chronic opioid users after discontinuation of opioids.

  Baseline (prior to opioid discontinuation) and 7 days post-opioid discontinuation

Study Arms (1)

patients under treatment with opioids referred for study of non-obstructive dysphagia for esophageal

OTHER

In patients with dysphagia referred for esophageal manometry as part of routine clinical practice, if esophageal dysfunction associated with opioid use is diagnosed, such as type III achalasia, esophagogastric junction outflow obstruction, esophageal spasm, or hypercontractile esophagus, the opioid is discontinued and replaced with another analgesic for 7 days. Esophageal manometry is then repeated to determine if the opioid-induced esophageal dysfunction (OIED) has resolved or persists.

Drug: The intervention involves the discontinuation of the opioid.

Interventions

The intervention involves the discontinuation of the opioid. DRUG

Patients with dysphagia and esophageal manometry indicating opioid-induced esophageal dysfunction (OIED) will have the opioid discontinued, and esophageal manometry will be repeated.

patients under treatment with opioids referred for study of non-obstructive dysphagia for esophageal

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with dysphagia on chronic treatment with opioids referred for study using high-resolution esophageal manometry in our motility laboratory

You may not qualify if:

• Those patients who, due to comorbidities, cannot suspend opioid treatment,
• Patients who do not wish to participate,
• Patients who present any symptoms suggestive of withdrawal or who are not able to suspend opioid treatment due to increased pain or discomfort during the seven days prior to the study
• Patients who have received any definitive treatment for the previously diagnosed motor disorder. (pe. Heller myotomy)
• Patients with gastroesophageal junction surgeries (e.g. Nissen type fundoplication)
• Patients with major esophageal endoscopic procedures (e.g. peroral endoscopic myotomy POEM).

Sponsors & Collaborators

• Hospital Clinic of Barcelona: lead
• Vall Hebron Insitut Recerca: collaborator

Study Sites (1)

Hospital Clínic of Barcelona

Barcelona, 08036, Spain

Location

Related Publications (4)

• Snyder DL, Crowell MD, Horsley-Silva J, Ravi K, Lacy BE, Vela MF. Opioid-Induced Esophageal Dysfunction: Differential Effects of Type and Dose. Am J Gastroenterol. 2019 Sep;114(9):1464-1469. doi: 10.14309/ajg.0000000000000369.

  PMID: 31403963 RESULT

• Snyder DL, Vela MF. Impact of opioids on esophageal motility. Neurogastroenterol Motil. 2023 May;35(5):e14587. doi: 10.1111/nmo.14587. Epub 2023 Apr 15.

  PMID: 37060333 RESULT

• Kraichely RE, Arora AS, Murray JA. Opiate-induced oesophageal dysmotility. Aliment Pharmacol Ther. 2010 Mar;31(5):601-6. doi: 10.1111/j.1365-2036.2009.04212.x. Epub 2009 Dec 8.

  PMID: 20003176 RESULT

• Ezquerra-Duran A, Alcala-Gonzalez L, Araujo IK, Alcedo J, Serra J, Barba-Orozco E. Prospective Evaluation of Opioid Cessation in Patients With Suspected Opioid-Induced Esophageal Dysfunction. Am J Gastroenterol. 2025 Jan 10;120(6):1400-1404. doi: 10.14309/ajg.0000000000003297.

  PMID: 39791564 DERIVED

MeSH Terms

Conditions

Deglutition Disorders

Condition Hierarchy (Ancestors)

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Pharyngeal Diseases; Otorhinolaryngologic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Neurogastroenterology and Motility section, Gastroenterology department

Model Details: In patients under regular treatment with opioids referred to the motility unit for dysphagia, esophageal manometry is performed and if they present an OIED, the morphine is removed and the manometry is repeated to evaluated if OIED was resolved with the suspension of opioid

Study Record Dates

• First Submitted: June 30, 2024
• First Posted: July 26, 2024
• Study Start: November 1, 2020
• Primary Completion: February 1, 2024
• Study Completion: August 31, 2024
• Last Updated: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)