Working… Menu

Opioid Effects on Swallowing and Esophageal Sphincter Pressure

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01191645
Recruitment Status : Completed
First Posted : August 31, 2010
Last Update Posted : February 2, 2012
Information provided by (Responsible Party):
Johanna Savilampi, Region Örebro County

Brief Summary:
The purpose of this study is to determine whether a dopamine receptor antagonist metoclopramide can counteract opioid induced effects on esophageal motility and lower esophageal sphincter. The aim of this study is also to evaluate if the opioid antagonist naloxone reduces the opioid induced pharyngeal and esophageal dysfunction.

Condition or disease Intervention/treatment Phase
Opioid Induced Pharyngeal and Esophageal Dysfunction Drug: naloxone Drug: remifentanil Drug: Sodium Chloride Drug: metoclopramide 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 effect of opioid antagonists on the opioid induced pharyngeal dysfunction and lower esophageal sphincter pressure are unknown. In a recently performed clinical trial we found that the peripheral opioid antagonist methylnaltrexone didn't have effect on the pharyngeal induced pharyngeal and esophageal dysfunction.This indicates that the negative opioid induced effects are not peripherally induced or mediated via peripheral opioid receptors.

In previously performed studies most of the volunteers reported swallowing problems when receiving infusion of the opioid remifentanil, we have also found that remifentanil abolished spontaneous esophageal motility.

The purpose of the study is to evaluate if opioid induced effects on the lower esophageal sphincter can be counteracted by a dopamine receptor antagonist, metoclopramide. It is previously known that dopamine, a catecholamine neurotransmitter, decreases the lower esophageal sphincter pressure and that a dopamine antagonist has the ability to increase the pressure.

Further in this study we want to evaluate if the opioid antagonist naloxone, which affects both peripheral and central opioid receptors, reduces the opioid induced pharyngeal and esophageal dysfunction.

A third aim of the study is to evaluate if the previously reported swallowing difficulties during infusion of opioid remifentanil are dose related, consequently does a higher concentration of opioids increase the swallowing difficulties.

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 three years.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Can Opioid Induced Effects on Esophageal Motility and Lower Esophageal Sphincter be Counteracted by a Dopamine Receptor Antagonist?
Study Start Date : October 2010
Actual Primary Completion Date : November 2010
Actual Study Completion Date : November 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Primperan Drug: metoclopramide
Injection fluid, solution 5 mg/mg Iv injection 0,2 mg/kg at one occasion
Other Name: Primperan

Active Comparator: Naloxon Drug: naloxone
Injection fluid, solution 0,4 mg/kg Bolus infusion 6ug/kg at one occasion Continuous infusion 0,1 ug/kg/minute during 50 min
Other Names:
  • Naloxon
  • ACT-code: V03AB15

Placebo Comparator: Natriumklorid Drug: Sodium Chloride
Infusion fluid, solution 9 mg/ml ( hydrogenic solution )
Other Names:
  • Natriumklorid
  • ACT-code: B05XA03

Experimental: Ultiva Drug: remifentanil
Powder for injection/ infusion fluid solution, 2 mg Infusion TCI 1ng/kg 10 min ( 0,05 ug/kg/min) Infusion TCI 2ng/kg 10 min ( 0.10 ug/kg/min) Infusion TCI 3ng/kg 20 min ( 0,15 ug/kg/min)
Other Names:
  • Ultiva
  • ATC-code: N01AH06

Primary Outcome Measures :
  1. Lower esophageal sphincter pressure [ Time Frame: 2 hours ]

Secondary Outcome Measures :
  1. Swallowing difficulties [ Time Frame: 2 hours ]
    The volunteers will be asked to do dry swallowing and assess the swallowing difficulty on the basis of following criteria: no difficulties, mild, moderate or severe difficulties.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  1. 18 - 40 year old healthy volunteers from both sexes.
  2. Have signed and dated Informed Consent.
  3. Willing and able to comply with the protocol for the duration of the trial.

Exclusion Criteria:

  1. Anamnesis of pharyngoesophageal dysfunction
  2. Known history of cardiac, pulmonary or neurological disease
  3. Ongoing medication
  4. Allergies to or history of reaction to naloxone, remifentanil, fentanyl analogues or metoclopramide
  5. Pregnancy or breast feeding
  6. BMI > 30
  7. Previous participation in a medical clinical trial where opioid has been used or have during last 30 days participated in any other medicinal clinical trial or in a trial where follow-up in not completed.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01191645

Layout table for location information
Örebro University Hospital
Örebro, Sweden, 70185
Sponsors and Collaborators
Region Örebro County
Layout table for investigator information
Principal Investigator: Magnus Wattwil, MD University Hospital Örebro

Layout table for additonal information
Responsible Party: Johanna Savilampi, MD, Region Örebro County Identifier: NCT01191645     History of Changes
Other Study ID Numbers: JS002
First Posted: August 31, 2010    Key Record Dates
Last Update Posted: February 2, 2012
Last Verified: January 2012
Keywords provided by Johanna Savilampi, Region Örebro County:
Lower esophageal sphincter pressure
Esophageal motility
High resolution solid state manometry
Additional relevant MeSH terms:
Layout table for MeSH terms
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists
Autonomic Agents
Gastrointestinal Agents
Dopamine D2 Receptor Antagonists
Dopamine Antagonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action