Opioid-Induced Hyperalgesia
Conditions
Keywords
opioid-induced hyperalgesia, methadone, gabapentin, opioid addiction
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.
Interventions
DRUGGabapentin;
Gabapentin titrated to daily dose of 2400mg PO over 1 week with established dose taken daily for 5 weeks.
DRUGPlacebo
Placebo titrated over 1 week with established dose taken daily for 5 weeks.
Sponsors
University of California, Los Angeles
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Pain Threshold Time From Baseline to Week 5 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gabapentin Gabapentin titrated to 2400 mg daily PO for 5 weeks | 10 |
| Placebo Matched placebo group underwent identical 'titration' as intervention group. | 16 |
| Total | 26 |
Baseline characteristics
| Characteristic | Placebo | Gabapentin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 10 Participants | 26 Participants |
| Age Continuous | 49.5 years STANDARD_DEVIATION 4.96 | 45.5 years STANDARD_DEVIATION 4.46 | 47.9 years STANDARD_DEVIATION 5.05 |
| Region of Enrollment United States | 16 participants | 10 participants | 26 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 9 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 16 |
| serious Total, serious adverse events | 0 / 10 | 0 / 16 |
Outcome results
Primary
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.
Time frame: baseline, 5 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gabapentin | Change in Pain Threshold Time From Baseline to Week 5 | 2.95 seconds | Standard Error 2.41 |
| Placebo | Change in Pain Threshold Time From Baseline to Week 5 | -3.49 seconds | Standard Error 2.85 |