Opioids and Esophageal Function

• ClinicalTrials.gov Identifier: NCT01012960
• Recruitment Status: Completed
• First Posted: November 13, 2009
• Last Update Posted: December 9, 2011
• Sponsor: Region Örebro County
• Collaborator: Wyeth is now a wholly owned subsidiary of Pfizer
• Information provided by (Responsible Party): Johanna Savilampi, Region Örebro County

Study Description

Brief Summary:

The purpose of this study is to evaluate if opioid-induced effects on the pharynx and esophagus is centrally or peripherally mediated.

Condition or disease	Intervention/treatment	Phase
Pharyngeal Dysfunction; Esophageal Dysfunction	Drug: methylnaltrexone	Phase 4

Detailed Description:

Opioids induce pharyngeal and esophageal dysfunction and reduce the lower esophageal sphincter (LES) pressure, and thereby decreases the barrier pressure between the stomach and esophagus. This contributes to an increased risk of regurgitation and aspiration during anaesthesia induction and in the postoperative period, when the patient is treated with opioids for pain relief. The effects of opioid antagonists on the opioid induced pharyngeal dysfunction and lower esophageal sphincter pressure are unknown. Therefore it is of great clinical value to evaluate if these negative effects are reversed by peripheral opioid antagonist, methylnaltrexone.

Methylnaltrexone is one of the newer agents of peripherally acting opioid antagonists that act to reverse some of the side effects of opioid drugs, such as constipation, without affecting analgesia.

If the opioid induced pharyngeal and esophageal dysfunction and reduction of the lower esophageal sphincter pressure is peripherally induced or mediated via peripheral opioid receptors, methylnaltrexone might reverse these effects and thereby reduce postoperative morbidity by reducing pulmonary complications. On the other hand, if the dysfunction is centrally induced and not mediated via peripheral opioid receptors there is no effect of methylnaltrexone.

The pharyngeal and esophageal motility/function can be registered in an easy and objective way with the high resolution manometry, ManoScan 360. ManoScan 360 is an equipment with 36 sensors at 1 cm spacing with 12 tip transducers at every sensor. The 36 closely spaced sensors automatically capture all relevant motor function from the pharynx to the stomach. The system collects reliable and consistent data records with improved diagnostic accuracy, and the data are analyzed using ManoView analyzes software. ManoScan 360 has a CE mark approval and has been used at Örebro University Hospital during the last two years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Is the Opioid-induced Pharyngeal and Esophageal Dysfunction Peripherally or Central Mediated?
• Study Start Date: November 2009
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: January 2010

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Placebo= normal saline	Drug: methylnaltrexone; 0,15 mg/kg sc ( subcutaneously)once per volunteer; Other Name: Relistor
Active Comparator: methylnaltexone; peripheral opioid antagonist	Drug: methylnaltrexone; 0,15 mg/kg sc ( subcutaneously)once per volunteer; Other Name: Relistor

Outcome Measures

Primary Outcome Measures :

1. Does methylnaltrexone influence the upper and lower esophageal sphincter pressure and the swallowing function following opioid administration? [ Time Frame: 6 hours per volunteer ]

Secondary Outcome Measures :

1. Does methylnaltrexone influence the experience of swallowing function following opioid administration? [ Time Frame: 6 hours per volunteer ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 40 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 18 -40 year old healthy volunteers from both sexes.
• have signed and dated Informed Consent.
• willing and able to comply with the protocol for the duration of the trial.

Exclusion Criteria:

• anamnesis of pharyngoesophageal dysfunction.
• known or history of cardiac, pulmonary or neurological disease.
• ongoing medication.
• allergies to or history of reaction to methylnaltrexone, remifentanil or fentanyl analogues.
• pregnancy or breast feeding.
• participation in another clinical medicinal trial during the last 30 days or where follow-up is not completed.

Contacts and Locations

Locations

Sweden

Department of Anaesthesiology, University Hospital Örebro

Örebro, Sweden, 701 85

University Hospital Örebro

Örebro, Sweden, 701 85

Sponsors and Collaborators

Region Örebro County

Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Principal Investigator: Magnus Wattwil, MD; University Hospital Örebro

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Savilampi J, Ahlstrand R, Magnuson A, Wattwil M. Effects of remifentanil on the esophagogastric junction and swallowing. Acta Anaesthesiol Scand. 2013 Sep;57(8):1002-9. doi: 10.1111/aas.12134. Epub 2013 May 29.

• Responsible Party: Johanna Savilampi, MD, Region Örebro County
• ClinicalTrials.gov Identifier: NCT01012960 History of Changes
• Other Study ID Numbers: JS001
• First Posted: November 13, 2009
• Last Update Posted: December 9, 2011
• Last Verified: December 2011

Keywords provided by Johanna Savilampi, Region Örebro County:

methylnaltrexone; upper esophageal sphincter; lower esophageal sphincter; high resolution solid state manometry; opioid induced pharyngeal and esophageal dysfunction

Additional relevant MeSH terms:

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Analgesics, Opioid; Methylnaltrexone; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Narcotic Antagonists