Opioid UsePhase 3NCT06522633
Esophageal Dysfunction Associated With Opioids: Clinical Response and Manometric Findings After Opioid Discontinuation
A Phase 3 study testing The intervention involves the discontinuation of the opioid. in people with Opioid Use, run by Hospital Clinic of Barcelona at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Opioid Use
- What is being tested?
- The intervention involves the discontinuation of the opioid.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSpain
- Study dates
- 1 Nov 2020to 31 Aug 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with dysphagia on chronic treatment with opioids referred for study using high-resolution esophageal manometry in our motility laboratory
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Prospective Evaluation of Opioid Withdrawal in Patients With Suspected Opioid-induced Esophageal Dysfunction (OIED)
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.
Read more
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.
Read the 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.
- Conditions
- Opioid Use
- Being tested
- The intervention involves the discontinuation of the opioid.
- Keywords
- Opioid-Associated Esophageal Dysfunction, dysphagia, esophageal motility
- Medical subject headings
- Deglutition Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: The intervention involves the discontinuation of the opioid. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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.
Measured: Baseline (prior to opioid discontinuation) and 7 days post-opioid discontinuation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2024
- Study start1 Nov 2020
- Primary completion1 Feb 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Opioid UseStudies of the same condition, open and under way.
- More trials run by Hospital Clinic of BarcelonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Clinic of Barcelona
- Sponsor type
- University, hospital or other
- Collaborators
- Vall Hebron Insitut Recerca
- Responsible party
- Principal investigator, Elizabeth Barba, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06522633
- Sponsor's protocol ID
- HCB/2022/0458
- Status last verified
- Oct 2024
- First submitted
- 30 Jun 2024
- Last updated
- 9 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31403963Snyder 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.
PubMed 37060333Kraichely 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.
PubMed 20003176Ezquerra-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.
PubMed 39791564
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of Opioid Withdrawal in Patients With Suspected Opioid-induced Esophageal Dysfunction (OIED)
- ClinicalTrials.gov ID
- NCT06522633
- Acronym / sponsor ID
- HCB/2022/0458
- Conditions
- Opioid Use
- Keywords
- Opioid-Associated Esophageal Dysfunction, dysphagia, esophageal motility
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Hospital Clinic of BarcelonaUniversity, hospital or other
- Collaborators
- Vall Hebron Insitut Recerca
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 1 Feb 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 26 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| patients under treatment with opioids referred for study of non-obstructive dysphagia for esophageal | Other | Drug: The 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with dysphagia on chronic treatment with opioids referred for study using high-resolution esophageal manometry in our motility laboratory
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| The intervention involves the discontinuation of the opioid.Patients with dysphagia and esophageal manometry indicating opioid-induced esophageal dysfunction (OIED) will have the opioid discontinued, and esophageal manometry will be repeated. | Drug | patients under treatment with opioids referred for study of non-obstructive dysphagia for esophageal |
Primary outcome
Improvement in Esophageal Motility Demonstrate the improvement in esophageal motility in chronic opioid users after discontinuation of opioids.
Time frame: 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.
1 secondary outcome
Improvement in Dysphagia Severity Demonstrate the improvement in dysphagia severity in chronic opioid users after discontinuation of opioids.
Time frame: Baseline (prior to opioid discontinuation) and 7 days post-opioid discontinuation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2024.
- Results publication: PubMed 31403963Snyder 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.
- Results publication: PubMed 37060333Snyder 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.
- Results publication: PubMed 20003176Kraichely 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.
- Derived from this study: PubMed 39791564Ezquerra-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing The intervention involves the discontinuation of the opioid. in people with Opioid Use, run by Hospital Clinic of Barcelona at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Improvement in Esophageal Motility Demonstrate the improvement in esophageal motility in chronic opioid users after discontinuation of opioids. (time frame: Baseline (prior to opioid discontinuation) and 7 days post-opioid discontinuation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06522633, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2024.