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

• ClinicalTrials.gov Identifier: NCT01210079
• Recruitment Status: Completed
• First Posted: September 28, 2010
• Results First Posted: April 6, 2012
• Last Update Posted: April 6, 2012
• Sponsor: University of California, Los Angeles
• Information provided by (Responsible Party): Peggy Compton, University of California, Los Angeles

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Opioid-Induced Hyperalgesia	Drug: Gabapentin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hyperalgesia in Methadone-Maintained Patients: Can it be Treated?
• Study Start Date: September 2002
• Actual Primary Completion Date: March 2008
• Actual Study Completion Date: May 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Gabapentin	Drug: Gabapentin; Gabapentin titrated to daily dose of 2400mg PO over 1 week with established dose taken daily for 5 weeks.
Placebo Comparator: Placebo	Drug: Placebo; Placebo titrated over 1 week with established dose taken daily for 5 weeks.

Outcome Measures

Primary Outcome Measures :

1. Change in Pain Threshold Time From Baseline to Week 5 [ Time Frame: baseline, 5 weeks ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 21 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Potential participants must:

1. Be between the ages of 21 and 55 years of age.
2. DSM-IVR diagnosis of prescription opioid abuse or dependence disorder
3. Be compliant in methadone treatment
4. On a stable dose of methadone at least 6 weeks.
5. Have provided random urine samples absent of any non-prescribed drugs of abuse x 2 months
6. 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.
7. Be agreeable to and capable of signing an informed consent.

Exclusion Criteria:

Potential participants must not:

1. Have known sensitivity to gabapentin.
2. Be substance dependent on alcohol, benzodiazepine, methamphetamine, cocaine or other drugs of abuse (except nicotine).
3. 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.
4. Be acutely psychotic, severely depressed and in need of inpatient treatment, or an immediate suicide risk.
5. Have a neurological or psychiatric illness (i.e., schizophrenia, Raynaud's disease, urticaria, stroke) that would affect pain responses.
6. Be currently taking opioid analgesic medication for a painful condition on a regular basis.
7. 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.
8. Have a current or past history of high blood pressure, heart disease, stroke or currently have a pacemaker.

Contacts and Locations

Locations

United States, California

UCLA School of Nursing

Los Angeles, California, United States, 90095

Sponsors and Collaborators

University of California, Los Angeles

Investigators

• Principal Investigator: Margaret (Peggy) A Compton, RN, PhD; University of California, Los Angeles

More Information

• Responsible Party: Peggy Compton, Professor, Associate Dean for Academic Affairs, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01210079
• Other Study ID Numbers: R01 DA 05463
• First Posted: September 28, 2010
• Results First Posted: April 6, 2012
• Last Update Posted: April 6, 2012
• Last Verified: February 2012

Keywords provided by Peggy Compton, University of California, Los Angeles:

opioid-induced hyperalgesia; methadone; gabapentin; opioid addiction

Additional relevant MeSH terms:

Hyperalgesia; Somatosensory Disorders; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Gabapentin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimanic Agents