Hyperalgesia in Methadone Patients: Can it be Treated?

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2008 by National Institute on Drug Abuse (NIDA).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier:
NCT00333242
First received: June 1, 2006
Last updated: August 11, 2008
Last verified: August 2008
  Purpose

In the proposed study, we will build upon our previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing a double-blind, placebo-controlled designs, the proposed work will evaluate the ability of dextromethorphan , an N-methyl-D-aspartate (NMDA)-antagonists to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, dextromethorphan, theorized to interfere with the development of opioid-induced hyperalgesia 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 trough 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 Intervention Phase
Opioid-Induced Hyperalgesia
Drug: dextromethorphan
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by National Institute on Drug Abuse (NIDA):

Primary Outcome Measures:
  • Pain tolerance [ Time Frame: 6 week ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pain threshold [ Time Frame: 6 week ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: September 2002
Primary Completion Date: August 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: dextromethorphan
    dextromethorphan PO titrated to 480 mg/day x 5 weeks
Detailed Description:

Addressing the undertreatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01-115). In fact, the undertreatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the undertreatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced.

In the proposed series of studies, the Principal Investigator (a first-time R01 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)-antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each 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 trough 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion criteria: Potential participants must:

    1. Be between the ages of 18 and 55 years of age.
    2. Fulfill DSM-IV criteria for opiate dependence.
    3. Be compliant in MM treatment and on a stable dose of methadone x 6 weeks.
    4. 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.
    5. Be agreeable to and capable of signing an informed consent.

Exclusion Criteria:

  • Exclusion Criteria: Potential participants must not:

    1. Have known sensitivity to dextromethorphan, gabapentin or oxycodone.
    2. Be dependent on alcohol, benzodiazepine 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., peripheral neuropathy, schizophrenia, neuropathic pain, Raynaud's disease, urticaria,) that would affect pain responses.
    6. Be currently taking analgesic medication (opioid or otherwise) 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00333242

Locations
United States, California
UCLA School of Nursing
Los Angeles, California, United States, 90095
Sponsors and Collaborators
Investigators
Principal Investigator: Margaret A Compton, RN, PhD UCLA School of Nursing
  More Information

No publications provided

Responsible Party: Margaret (Peggy) Compton RN PhD, UCLA School of Nursing
ClinicalTrials.gov Identifier: NCT00333242     History of Changes
Other Study ID Numbers: R01-DA15463-04
Study First Received: June 1, 2006
Last Updated: August 11, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute on Drug Abuse (NIDA):
Pain
opioid
hyperalgesia
methadone

Additional relevant MeSH terms:
Hyperalgesia
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Dextromethorphan
Methadone
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses
Respiratory System Agents
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Depressants
Narcotics

ClinicalTrials.gov processed this record on April 22, 2014