Opioid Effects on Swallowing and Esophageal Sphincter Pressure

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johanna Savilampi, University Hospital Orebro
ClinicalTrials.gov Identifier:
NCT01191645
First received: August 30, 2010
Last updated: January 31, 2012
Last verified: January 2012
  Purpose

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 Intervention Phase
Opioid Induced Pharyngeal and Esophageal Dysfunction
Drug: naloxone
Drug: remifentanil
Drug: Sodium Chloride
Drug: metoclopramide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Can Opioid Induced Effects on Esophageal Motility and Lower Esophageal Sphincter be Counteracted by a Dopamine Receptor Antagonist?

Resource links provided by NLM:


Further study details as provided by University Hospital Orebro:

Primary Outcome Measures:
  • Lower esophageal sphincter pressure [ Time Frame: 2 hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Swallowing difficulties [ Time Frame: 2 hours ] [ Designated as safety issue: No ]
    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.


Enrollment: 14
Study Start Date: October 2010
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01191645

Locations
Sweden
Örebro University Hospital
Örebro, Sweden, 70185
Sponsors and Collaborators
University Hospital Orebro
Investigators
Principal Investigator: Magnus Wattwil, MD University Hospital Örebro
  More Information

No publications provided

Responsible Party: Johanna Savilampi, MD, University Hospital Orebro
ClinicalTrials.gov Identifier: NCT01191645     History of Changes
Other Study ID Numbers: JS002
Study First Received: August 30, 2010
Last Updated: January 31, 2012
Health Authority: Sweden: Swedish National Council on Medical Ethics

Keywords provided by University Hospital Orebro:
Lower esophageal sphincter pressure
Esophageal motility
Remifentanil
Metoclopramide
Naloxone
High resolution solid state manometry

Additional relevant MeSH terms:
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Metoclopramide
Dopamine Antagonists
Naloxone
Remifentanil
Analgesics, Opioid
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Gastrointestinal Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Narcotic Antagonists
Sensory System Agents
Analgesics
Central Nervous System Depressants
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on July 22, 2014