Opioid-induced Hyperalgesia After Remifentanil Infusion

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Oslo University Hospital
Sponsor:
Information provided by (Responsible Party):
Marlin Comelon, Oslo University Hospital
ClinicalTrials.gov Identifier:
NCT01702389
First received: October 4, 2012
Last updated: October 6, 2012
Last verified: October 2012
  Purpose

Remifentanil is a rapid-acting opioid which has been widely used in pain treatment during surgery for the last 15 years 1. Remifentanil is rapidly eliminated (minutes) from the body after end of infusion, and this makes it easily manageable compared to other opioids. However, there are both experimental and clinical studies indicating that remifentanil, after end of infusion, triggers increased pain sensation and increased opioid consumption post-operatively. Increased post-operative opioid consumption should be avoided due to the adverse effects of these drugs (nausea/vomiting, pruritus, dizziness, fatigue and reduced respiratory rate). Thus, it's important to investigate relevant strategies to avoid the increased pain sensation (opioid-induced hyperalgesia = hypersensitivity to pain stimuli) after end of infusion of remifentanil after surgery. Several experimental and clinical trials have been conducted in this field. Ketamine has been shown to block this effect, but its adverse effect profile (i.a. hallucinations) makes it not suitable in normal clinical use. In a study of healthy volunteers, it has been demonstrated that parecoxib (a COX-2 selective NSAID) can prevent remifentanil-induced hyperalgesia. Our group has previously shown that a relatively COX-1 selective NSAID (ketorolac) can prevent hyperalgesia in an experimental pain model.

This is of interest since NSAIDs are frequently administered as premedication before surgery. There are several disadvantages associated with the use of COX-2 inhibitors, e.g. the risk of myocardial infarction after long-term use (> 1 year), and potentially reduced bone healing after orthopedic surgery. However, this has not been shown with short-term use (days/week). The disadvantages associated with the use of e.g. ketorolac (a COX-1 inhibitor) are i.a. increased bleeding tendency, which is unfavourable for the surgeon, and increased risk of gastric ulcer. Therefore, it is of interest to investigate other ways of preventing opioid-induced hyperalgesia. In a recent animal study it has been shown that gradual dose reduction of remifentanil (vs. abrupt withdrawal of a relatively high remifentanil dose) can prevent the development of hyperalgesia after end of infusion. In this study we will i.a. investigate whether this is also the case in humans. In this new model, the study participants will get remifentanil infusion with two different dose reduction regimes: gradual reduction or abrupt withdrawal.


Condition Intervention Phase
Opioid Induced Hyperalgesia
Drug: Remifentanil
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Can Opioid-induced Hyperalgesia be Prevented by Gradual Dose Reduction vs. Abrupt Withdrawal of Remifentanil?

Resource links provided by NLM:


Further study details as provided by Oslo University Hospital:

Primary Outcome Measures:
  • Hyperalgesia measured by numeric rating scale for pain [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]

    Two pain models will be used - a heat-pain and a cold-pain model. Testing will be done before, during and after remifentanil infusion. NRS (Numeric rating Scale) will be used for pain scoring.

    Heat model:

    A computer-controlled Medoc ATS Thermal stimulator (3 x 3 cm) is applied to the left volar forearm at pre-defined areas.

    Cold model:

    In the cold test the study participant should keep his right hand in circulating cold water (3 ̊C) in up to 90 seconds.

    The pain models will be applied during three separate trials using remifentanil infusion with abrupt withdrawal, remifentanil infusion with gradual withdrawal and saline infusion(placebo).



Estimated Enrollment: 16
Study Start Date: October 2012
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Remifentanil
The study has only one arm. Same group of volunteers will receive remifentanil infusion with abrupt withdrawal, remifentanil infusion with gradual dose reduction and saline infusion at three separate trials.
Drug: Remifentanil
Other Name: Ultiva

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male
  • Age 18-60
  • Body mass index 17-30
  • Healthy volunteers

Exclusion Criteria:

  • Use of medication; alternative medicine
  • Substance abuse
  • Allergies towards medication used in the study
  • Participation in other clinical studies the previous 6 months
  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: NCT01702389

Contacts
Contact: Marlin Comelon, MD +4722119690 marlin.comelon@gmail.com
Contact: Harald Lenz, PhD, MD +4722119690 UXHANZ@ous-hf.no

Locations
Norway
Oslo University Hospital Recruiting
Oslo, Norway, 0424
Contact: Marlin Comelon, MD    +4722119690    marlin.comelon@gmail.com   
Contact: Harald Lenz, PhD, MD    +4722119690    UXHANZ@ous-hf.no   
Principal Investigator: Marlin Comelon, MD         
Sub-Investigator: Harald Lenz, PhD, MD         
Sub-Investigator: Johan C Raeder, PhD, MD         
Sub-Investigator: Tomas Draegni, CPRN         
Sub-Investigator: Audun Stubhaug, PhD, MD         
Sponsors and Collaborators
Oslo University Hospital
Investigators
Principal Investigator: Marlin Comelon, MD Oslo UH
  More Information

Publications:

Responsible Party: Marlin Comelon, Principal Investigator, Oslo University Hospital
ClinicalTrials.gov Identifier: NCT01702389     History of Changes
Other Study ID Numbers: 2011/1639, 2011-002734-39, 11/14666
Study First Received: October 4, 2012
Last Updated: October 6, 2012
Health Authority: Norway: The Regional Comitees for Medical and Health Research Ethics in Norway.
Norway: Norwegian Medicines Agency

Keywords provided by Oslo University Hospital:
opioid induced hyperalgesia
Pain
Postoperative pain
Hyperalgesia

Additional relevant MeSH terms:
Hyperalgesia
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Remifentanil
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Hypnotics and Sedatives
Anesthetics, Intravenous
Anesthetics, General
Anesthetics

ClinicalTrials.gov processed this record on August 28, 2014