Memantine for Post-Operative Pain Control

Pain is a common element of surgery. Opiates (morphine, oxycodone, hydrocodone, methadone, fentanyl) are very helpful in decreasing pain after surgery. Unfortunately, with repeated use opiates lose their effectiveness, such that patients need to utilize more opiates to achieve adequate pain relief - a phenomenon called tolerance. Sometimes tolerance to a pain reliever's effects can develop in just a few hours. It is thought that activation of the N-methyl d-aspartate (NMDA) receptor, a "switch" found on the surface of nerves, is partially responsible for opiate tolerance. Memantine is a medication that limits the activity of NMDA receptors in the brain and spinal cord. It has been used for years to help patients with Alzheimer's Disease. In this study, we will study the effects of memantine when combined with opiate medications to see whether it can increase the effectiveness of opiates for pain after surgery and reduce the side effects caused by opiates (e.g., sedation, nausea, itching).

Study Overview

• Status: Unknown
• Conditions: Pain, Post-operative
• Intervention / Treatment: Drug: Memantine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • University of Washington Medical Center
      • Contact: Lydia Stout, BA; Phone Number: 206-914-9253; Email: lstout@uw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Surgery for total hip replacement, knee replacement OR lumbar spinal fusion
• Taking no opiate medication OR taking opiate medication for at least 6 weeks

Exclusion Criteria:

• History of alcohol or drug abuse
• Clinical diagnosis of Alzheimer's Disease
• Prior adverse reaction to memantine
• Severe renal impairment (creatinine clearance <30 ml/min)
• Inability to give informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Opiate Naive; Subjects who have not taken opiate medication in previous 6 weeks before surgery	Drug: Memantine; 7 days prior to surgery, start taking 5mg memantine daily; 4 days prior to surgery, increase dose to 5mg twice daily; 2 days prior to surgery, increase dose to 10mg in the morning, and 5 mg in the evening; on the day of surgery, increase dose to 10mg twice daily, and continue on this dose until 14 days after surgery.; Other Names: Namenda; Drug: Placebo; 7 days prior to surgery, start taking one placebo tablet daily; 4 days prior to surgery, increase dose to one placebo tablet twice daily; 2 days prior to surgery, increase dose to 2 placebo tablets in the morning, and one placebo tablet in the evening; on the day of surgery, increase dose to 2 placebo tablets in the morning and 1 placebo tablet in the evening. On the first day after surgery through 14 days after surgery, take 1 placebo tablet twice daily.
ACTIVE_COMPARATOR: Opiate tolerant; Subjects who have taken opiate medications for the 6 weeks before surgery	Drug: Memantine; 7 days prior to surgery, start taking 5mg memantine daily; 4 days prior to surgery, increase dose to 5mg twice daily; 2 days prior to surgery, increase dose to 10mg in the morning, and 5 mg in the evening; on the day of surgery, increase dose to 10mg twice daily, and continue on this dose until 14 days after surgery.; Other Names: Namenda; Drug: Placebo; 7 days prior to surgery, start taking one placebo tablet daily; 4 days prior to surgery, increase dose to one placebo tablet twice daily; 2 days prior to surgery, increase dose to 2 placebo tablets in the morning, and one placebo tablet in the evening; on the day of surgery, increase dose to 2 placebo tablets in the morning and 1 placebo tablet in the evening. On the first day after surgery through 14 days after surgery, take 1 placebo tablet twice daily.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in numerical ratings on pain diaries as outpatients (pre and post surgery)	For 1 week pre-surgery, through 2 weeks post-surgery
Daily pain numerical ratings at rest and with movement as inpatients.	Immediately post-surgery until discharge (2-3 days)
Total opiate dose via patient controlled IV hydromorphone	Post-surgery day 1
Oxycodone dose taken prn	Post-surgery day 2 through 3 months.

Secondary Outcome Measures

Outcome Measure	Time Frame
Treatment group differences in side effects (nausea, itching, sedation, urinary retention following foley catheter discontinuation)	One week pre-surgery through 3 months post-surgery
Changes in cognitive function, assessed with Digit-Symbol Substitution Test and Trail Making Test B	One week pre-surgery, immediately pre-surgery, and post-surgery days 1, 2, 3
Changes in pain and quality of life questionnaire responses (SF-McGill-2, Brief Pain Questionnaire, SF-36 v2)	One week pre-surgery through 3 months post-surgery, particularly as outpatient

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: Forest Laboratories
• Investigators: Principal Investigator: Gregory Terman, MD, PhD, University of Washington Department of Anesthesiology and Pain Medicine

Publications and helpful links

General Publications

• Grande LA, O'Donnell BR, Fitzgibbon DR, Terman GW. Ultra-low dose ketamine and memantine treatment for pain in an opioid-tolerant oncology patient. Anesth Analg. 2008 Oct;107(4):1380-3. doi: 10.1213/ane.0b013e3181733ddd.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ANTICIPATED): June 1, 2011
• Study Completion (ANTICIPATED): September 1, 2011

Study Registration Dates

• First Submitted: December 29, 2009
• First Submitted That Met QC Criteria: December 30, 2009
• First Posted (ESTIMATE): December 31, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 29, 2010
• Last Update Submitted That Met QC Criteria: June 25, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: Receptors, N-Methyl-D-Aspartate; Pain Measurement; Adjuvants, pharmaceuticals; Drug tolerance
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Memantine
• Other Study ID Numbers: 35063-A; NAM-MD-63