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

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT01210079
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arms: 2
• Duration (Months): 92
• Patients Per Site Per Month: 0.3

Study Details

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
• 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: Sep 1, 2002
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: May 1, 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 [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

Criteria

• Ages Eligible for Study: 21 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• 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: Sep 28, 2010
• Last Update Posted: Apr 6, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by Peggy Compton, Professor, Associate Dean for Academic Affairs, University of California, Los Angeles: opioid-induced hyperalgesia; methadone; gabapentin; opioid addiction
• Additional relevant MeSH terms: Hyperalgesia; Gabapentin

Study Results

Participant Flow

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	Gabapentin titrated to 2400 mg daily PO for 5 weeks	Matched placebo group underwent identical 'titration' as intervention group.
Period Title: Overall Study
STARTED	10	16
COMPLETED	10	16
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Gabapentin	Placebo	Total
Arm/Group Description	Gabapentin titrated to 2400 mg daily PO for 5 weeks	Matched placebo group underwent identical 'titration' as intervention group.	Total of all reporting groups
Overall Participants	10	16	26
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	16 100%	26 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.5 (4.46)	49.5 (4.96)	47.9 (5.05)
Sex: Female, Male (Count of Participants)
Female	5 50%	7 43.8%	12 46.2%
Male	5 50%	9 56.3%	14 53.8%
Region of Enrollment (participants) [Number]
United States	10 100%	16 100%	26 100%

Outcome Measures

1. Primary Outcome

Title	Change in Pain Threshold Time From Baseline to Week 5
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Gabapentin	Placebo
Arm/Group Description	Gabapentin titrated to 2400 mg daily PO for 5 weeks	Matched placebo group underwent identical 'titration' as intervention group.
Measure Participants	10	16
Mean (Standard Error) [seconds]	2.95 (2.41)	-3.49 (2.85)

Adverse Events

Arm/Group Title	Gabapentin		Placebo
Arm/Group Description	Gabapentin titrated to 2400 mg daily PO for 5 weeks		Matched placebo group underwent identical 'titration' as intervention group.
All Cause Mortality
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Gabapentin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/16 (0%)

Limitations/Caveats

Baseline hyperalgesia not established. Duration of trial only 5 weeks. Findings can only be generalized to methadone-maintained patients who are able to abstain from illicit drug use over an extended period of time.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.