Hyperalgesia in Methadone-Maintained Patients: Can it be Treated?

Study Overview
=================
Brief Summary
-----------------
Utilizing a double-blind, placebo-controlled design, the proposed work will evaluate the ability of an adjuvant anticonvulsant analgesic to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by Methadone-Maintained (MM) patients. Specifically, in a sample of MM patients, gabapentin, which has proven efficacy in treating neuropathic pain will be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia.

Official Title
-----------------
Hyperalgesia in Methadone-Maintained Patients: Can it be Treated?

Conditions
-----------------
Opioid-Induced Hyperalgesia

Intervention / Treatment
-----------------
* Drug: Gabapentin;
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Potential participants must: Be between the ages of 21 and 55 years of age. DSM-IVR diagnosis of prescription opioid abuse or dependence disorder Be compliant in methadone treatment On a stable dose of methadone at least 6 weeks. Have provided random urine samples absent of any non-prescribed drugs of abuse x 2 months Be in good physical health or in the case of a medical condition needing ongoing treatment, be in the care of a physician who is willing to take responsibility for such treatment. The same conditions apply in cases of patients with a psychiatric disorder needing ongoing treatment. Be agreeable to and capable of signing an informed consent. Exclusion Criteria: Potential participants must not: Have known sensitivity to gabapentin. Be substance dependent on alcohol, benzodiazepine, methamphetamine, cocaine or other drugs of abuse (except nicotine). Have any acute medical condition that would make participation medically hazardous, (e.g., acute hepatitis, unstable cardiovascular disease, liver or renal disease) or have liver enzyme values (AST or ALT) greater than 5 times normal range. Be acutely psychotic, severely depressed and in need of inpatient treatment, or an immediate suicide risk. Have a neurological or psychiatric illness (i.e., schizophrenia, Raynaud's disease, urticaria, stroke) that would affect pain responses. Be currently taking opioid analgesic medication for a painful condition on a regular basis. Be a nursing or pregnant female. Female of childbearing potential must agree to use a medically acceptable method of birth control, (e.g. oral contraceptives, barrier (diaphragm or condom) with or without spermicide, levonorgestrel implant, intra-uterine progesterone contraceptives system, medroxyprogesterone acetate contraceptive injection) or to complete abstinence. Females who become pregnant during the course of the study will be dropped from the study. Have a current or past history of high blood pressure, heart disease, stroke or currently have a pacemaker.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gabapentin<br> | Drug: Gabapentin;<br>* Gabapentin titrated to daily dose of 2400mg PO over 1 week with established dose taken daily for 5 weeks.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo titrated over 1 week with established dose taken daily for 5 weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Pain Threshold Time From Baseline to Week 5 | Change in pain threshold time from baseline (pre-gabapentin) to week 5 (post gabapentin)measured during cold pressor task administered at peak methadone blood levels. Pain threshold time is the amount of time that passes before pain is detected after administration of the cold pressor. | baseline, 5 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
opioid-induced hyperalgesia, methadone, gabapentin, opioid addiction