search
Back to results

Effects of N-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy

Primary Purpose

Hyperalgesia, Pain, Prostate Cancer

Status
Unknown status
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Amantadine
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional educational/counseling/training trial for Hyperalgesia focused on measuring Hyperalgesia, Quantitative Sensory Testing, Pain, Opioid use, Elderly

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Able to read and write English; Age 18-59 or >= 60 years; American Society of Anesthesiologists Class 1 to 3; Scheduled for elective radical prostatectomy; Body weight between 50-110 kg, body mass index (BMI) <= 30. Exclusion Criteria: Significant central nervous system (CNS), respiratory, cardiac, hepatic, renal or endocrine dysfunction and/or any significant sequelae; Contraindications, allergies to, and/or past adverse reactions to opioid analgesics, amantadine or nonsteroidal anti-inflammatory drugs (NSAIDS); Current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) Axis I disorder or cognitive dysfunction or history of this within the last year; History of epilepsy or other seizures; History of chronic pain of at least 6 months duration; History of long term opioid use for chronic pain of at least 6 months duration; History of long term use of amantadine or other antiparkinsonian drug; Ingestion of antitussive medication (dextromethorphan) within the 48 hours before surgery; History of alcohol or drug dependency/abuse of at least 6 months duration

Sites / Locations

  • University Health NetworkRecruiting

Outcomes

Primary Outcome Measures

To investigate the effects of perioperative NMDA receptor blockade on postoperative hyperalgesia, pain and analgesic consumption in young and elderly men

Secondary Outcome Measures

To assess age differences in the intensity and course of secondary hyperalgesia after surgery

Full Information

First Posted
September 9, 2005
Last Updated
March 13, 2006
Sponsor
University Health Network, Toronto
Collaborators
Canadian Institutes of Health Research (CIHR)
search

1. Study Identification

Unique Protocol Identification Number
NCT00188383
Brief Title
Effects of N-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy
Official Title
Effects of NMDA-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy in Young and Elderly Patients
Study Type
Interventional

2. Study Status

Record Verification Date
September 2005
Overall Recruitment Status
Unknown status
Study Start Date
January 2004 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 2006 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
University Health Network, Toronto
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

5. Study Description

Brief Summary
The primary aim is to determine whether perioperative NMDA-receptor antagonism has differential effects on postoperative pain, hyperalgesia and morbidity in younger and older patients. In order to achieve this aim, the researchers propose to conduct the first randomized, double-blind placebo-controlled study designed to investigate age differences in the effects of perioperative oral administration of an NMDA-receptor antagonist (amantadine) in men undergoing radical prostatectomy. In addition, age differences in psychosocial factors and the pharmacological properties of amantadine and morphine will be measured to control for, and clarify, their contribution to the differences found. The specific objectives of the study are to: investigate the effects of perioperative NMDA receptor blockade on postoperative hyperalgesia, pain and analgesic consumption in young and elderly men assess age differences in the intensity and course of secondary hyperalgesia after surgery
Detailed Description
The immediate postoperative period is associated with spontaneous pain and hyperalgesia, i.e., increased pain response (both intensity and duration) to normally painful stimuli following tissue injury or damage. The development and maintenance of secondary hyperalgesia depend on complex plastic changes in spinal cord dorsal horn cells after peripheral injury or damage. Afferent impulses signaling the damage are carried to the dorsal horn by slowly conducting, unmyelinated C-fibres. C-fibres release glutamate which acts at three receptor types: metabotropic, kainate/AMPA and NMDA. NMDA receptor activation, through a complex cascade of intracellular events, results in dorsal horn neuron hyperexcitability or central sensitization. These cells have increased spontaneous activity, decreased threshold, increased response to afferent input, prolonged afterdischarge to repeated stimulation, and an expansion of receptive fields. Central sensitization is expressed behaviorally as secondary hyperalgesia and contributes to prolonged postoperative pain. It also may trigger pathological reorganization of neural circuitry leading to the development of chronic postsurgical pain. Through these processes, tissue injury may have profound effects on the CNS that long outlast the injury. In animal models of pain, NMDA agonists induce central sensitization and hyperalgesia whereas antagonists decrease or prevent hyperalgesia. In humans, NMDA-receptor antagonism decreases secondary hyperalgesia subsequent to experimentally-induced pain. Perioperative administration of NMDA antagonists, that is, before, during and after surgery, may be the ideal intervention to block the initiation and maintenance of central sensitization. Several studies have found that this intervention reduces postoperative hyperalgesia, pain, and analgesic use; however, others have not found these effects. This is not surprising given the variability across studies in factors such as surgical procedure, extent and nature of tissue damage, duration of surgery, pharmacokinetics of the agent(s) tested, and intraoperative and postoperative analgesia. Nonetheless, the weight of the evidence suggests that preventing or minimizing central sensitization reduces pain and analgesic requirements. Co-administration of NMDA antagonists and opioids has been advocated as an effective approach. The combination of morphine and amantadine should reduce postoperative pain by inducing analgesia through actions on opioid-mediated receptor systems and by reducing hyperalgesia via NMDA receptor-mediated events . The combination also should produce fewer opioid-related adverse effects due to the anticipated opioid-sparing effect. The present proposal describes the first direct comparison of perioperative NMDA receptor blockade coupled with intra- and post-operative opioid administration in young and elderly patients. In order to minimize the influence of other perioperative factors on the outcome variables, all patients will undergo the same surgical procedure and anesthetic protocol. Furthermore, factors that cannot readily be standardized (e.g., surgical duration, mood) will be measured and controlled for statistically. This increases the internal validity of the proposed study and our ability to detect age and drug effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hyperalgesia, Pain, Prostate Cancer
Keywords
Hyperalgesia, Quantitative Sensory Testing, Pain, Opioid use, Elderly

7. Study Design

Primary Purpose
Educational/Counseling/Training
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
132 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Amantadine
Primary Outcome Measure Information:
Title
To investigate the effects of perioperative NMDA receptor blockade on postoperative hyperalgesia, pain and analgesic consumption in young and elderly men
Secondary Outcome Measure Information:
Title
To assess age differences in the intensity and course of secondary hyperalgesia after surgery

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to read and write English; Age 18-59 or >= 60 years; American Society of Anesthesiologists Class 1 to 3; Scheduled for elective radical prostatectomy; Body weight between 50-110 kg, body mass index (BMI) <= 30. Exclusion Criteria: Significant central nervous system (CNS), respiratory, cardiac, hepatic, renal or endocrine dysfunction and/or any significant sequelae; Contraindications, allergies to, and/or past adverse reactions to opioid analgesics, amantadine or nonsteroidal anti-inflammatory drugs (NSAIDS); Current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) Axis I disorder or cognitive dysfunction or history of this within the last year; History of epilepsy or other seizures; History of chronic pain of at least 6 months duration; History of long term opioid use for chronic pain of at least 6 months duration; History of long term use of amantadine or other antiparkinsonian drug; Ingestion of antitussive medication (dextromethorphan) within the 48 hours before surgery; History of alcohol or drug dependency/abuse of at least 6 months duration
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lucia Gagliese, PhD
Phone
416-340-4800
Ext
4296
Email
lucia.gagliese@uhn.on.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lucia Gagliese, PhD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lucia Gagliese, PhD
Phone
416-340-4800
Ext
4296
Email
lucia.gagliese@uhn.on.ca
First Name & Middle Initial & Last Name & Degree
Lucia Gagliese, PhD
First Name & Middle Initial & Last Name & Degree
Vincent Chan, MD
First Name & Middle Initial & Last Name & Degree
Dirk Snijedelaar, MD
First Name & Middle Initial & Last Name & Degree
Joel Katz, PhD
First Name & Middle Initial & Last Name & Degree
Gideon Koren, MD

12. IPD Sharing Statement

Learn more about this trial

Effects of N-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy

We'll reach out to this number within 24 hrs