Pain, Post-operative
Conditions
Keywords
Adjuvants, pharmaceuticals, Receptors, N-Methyl-D-Aspartate, Drug tolerance, Pain Measurement
Brief summary
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).
Interventions
DRUGMemantine
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.
DRUGPlacebo
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.
Sponsors
Forest Laboratories
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| Treatment group differences in side effects (nausea, itching, sedation, urinary retention following foley catheter discontinuation) | One week pre-surgery through 3 months post-surgery |
Countries
United States
Contacts
Primary ContactLydia Stout, BA
Outcome results
None listed