Opioids and Esophageal Function

Sponsor

Region Örebro County (Other)

Overall Status

Completed

CT.gov ID

NCT01012960

Collaborator

Wyeth is now a wholly owned subsidiary of Pfizer (Industry)

Enrollment

Locations

Arms

Duration (Months)

6.5

Patients Per Site

3.2

Patients Per Site Per Month

Study Details

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

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 :

Nov 1, 2009

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Jan 1, 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 Names: Relistor
Active Comparator: methylnaltexone peripheral opioid antagonist	Drug: methylnaltrexone 0,15 mg/kg sc ( subcutaneously)once per volunteer Other Names: Relistor

Arm

Intervention/Treatment

Placebo Comparator: Placebo

Placebo= normal saline

Drug: methylnaltrexone

0,15 mg/kg sc ( subcutaneously)once per volunteer

Other Names:

Relistor

Active Comparator: methylnaltexone

peripheral opioid antagonist

Drug: methylnaltrexone

0,15 mg/kg sc ( subcutaneously)once per volunteer

Other Names:

Relistor

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Does methylnaltrexone influence the experience of swallowing function following opioid administration? [6 hours per volunteer]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 40 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.