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

Phase 3
Completed
Conditions
Opioid Use
Interventions
Drug: The intervention involves the discontinuation of the opioid.
Registration Number
NCT06522633
Lead Sponsor
Hospital Clinic of Barcelona
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.

Detailed Description

Background and Current State of the Topic Chronic opioid consumption has been increasing significantly in recent years. While the side effects on the small intestine and colon are well-studied and well-established, their effects on the upper gastrointestinal tract are not fully understood, despite patients reporting numerous symptoms such as dysphagia, nausea, or chest pain. Recently, a new entity known as opioid-induced esophageal dysfunction has been described, defined as a motility disorder of the esophageal body or dysfunction of the sphincters in patients with chronic opioid use. Within this entity, the following motor disorders have been primarily observed: outflow tract obstruction, distal esophageal spasm, type III achalasia, and Jackhammer esophagus. However, more studies are needed to determine the prevalence of opioid-induced esophageal dysfunction in chronic opioid users, as well as to understand if opioids can cause other esophageal motor disorders besides those described. Although an association between chronic opioid use and an increase in the incidence of esophageal motor disorders has been demonstrated, there are no prospective studies proving that discontinuation of opioid treatment results in the resolution of the esophageal motor disorder.

Hypothesis During the performance of high-resolution esophageal manometries in our unit, we have observed a higher prevalence of motor disorders in patients who consume opioids. Our hypothesis, based on the available literature, is that most of these disorders can reverse upon discontinuation of opioid treatment without the need for more aggressive therapies. To test this hypothesis, a high-resolution manometry will be performed again after the patient has discontinued opioid treatment for at least 7 days.

Outcomes

Primary Outcome Measure:

Improvement in Esophageal Motility Description: Evaluate the improvement in esophageal motility in chronic opioid users after discontinuation of opioids.

Measurement Tool: High-resolution esophageal manometry (HREM). Unit of Measure: Manometric parameters (e.g., integrated relaxation pressure (IRP) in mmHg).

Secondary Outcome Measure:

Improvement in Dysphagia Severity Description: Assess the improvement in dysphagia severity in chronic opioid users after discontinuation of opioids.

Measurement Tool: Dysphagia Severity Score. Unit of Measure: Dysphagia score (e.g., a numeric scale from 0 to 10).

Description: Evaluate in chronic opioid users with esophageal motor disorders, the improvement in esophageal motility after discontinuation of opioids evaluated by high-resolution esophageal manometry.

Secondary outcome:

Determine if the symptoms that prompted the esophageal motility study disappear with the discontinuation of opioid treatment.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
20
Inclusion Criteria
  • Patients with dysphagia on chronic treatment with opioids referred for study using high-resolution esophageal manometry in our motility laboratory
Exclusion Criteria
  • 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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
patients under treatment with opioids referred for study of non-obstructive dysphagia for esophagealThe intervention involves the discontinuation of the opioid.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.
Primary Outcome Measures
NameTimeMethod
Improvement in Esophageal Motility Demonstrate the improvement in esophageal motility in chronic opioid users after discontinuation of opioids.Baseline (prior to opioid discontinuation) and 7 days post-opioid discontinuation

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.

Secondary Outcome Measures
NameTimeMethod
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

Change in dysphagia severity

-Assessment Tool: Dysphagia Severity Score. Unit of Measure: Dysphagia score (numeric scale). Assessment Points: Baseline (during opioid treatment) and after 7 days of opioid discontinuation.

Trial Locations

Locations (1)

Hospital Clínic of Barcelona

🇪🇸

Barcelona, Spain

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