Opioid-induced HyperalgesiaPhase 1NCT00333242
Hyperalgesia in Methadone Patients: Can it be Treated?
A Phase 1 study testing dextromethorphan in people with Opioid-induced Hyperalgesia, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Opioid-induced Hyperalgesia
- What is being tested?
- dextromethorphan
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2002to Aug 2006
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Be between the ages of 18 and 55 years of age.
- Fulfill DSM-IV criteria for opiate dependence.
- Be compliant in MM treatment and on a stable dose of methadone x 6 weeks.
- 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.
Who cannot join
- Have known sensitivity to dextromethorphan, gabapentin or oxycodone.
- Be dependent on alcohol, benzodiazepine 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., peripheral neuropathy, schizophrenia, neuropathic pain, Raynaud's disease, urticaria,) that would affect pain responses.
- Be currently taking analgesic medication (opioid or otherwise) 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA School of Nursing
Los Angeles, California, 90095
About this study
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.
Read the 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.
- Conditions
- Opioid-induced Hyperalgesia
- Being tested
- dextromethorphan
- Keywords
- Pain, opioid, hyperalgesia, methadone
- Medical subject headings
- Pain, Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dextromethorphanDrug
dextromethorphan PO titrated to 480 mg/day x 5 weeks
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain tolerance
Measured: 6 week
Secondary outcomes (1)
Pain threshold
Measured: 6 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2006 (estimated)
- Study startSep 2002
- Primary completionAug 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid-induced HyperalgesiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute on Drug Abuse (NIDA)
- Sponsor type
- US National Institutes of Health
- Investigators
- Margaret A Compton, RN, PhD, Principal investigator, UCLA School of Nursing
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00333242
- Sponsor's protocol ID
- R01DA015463-04
- Status last verified
- Aug 2008
- First submitted
- 1 Jun 2006
- Last updated
- 11 Jan 2017
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hyperalgesia in Methadone Patients: Can it be Treated?
- ClinicalTrials.gov ID
- NCT00333242
- Acronym / sponsor ID
- R01DA015463-04
- Conditions
- Opioid-induced Hyperalgesia
- Keywords
- Pain, opioid, hyperalgesia, methadone
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (actual)
- Lead sponsor
- National Institute on Drug Abuse (NIDA)US National Institutes of Health
- Study start
- Sep 2002
- Primary completion
- Aug 2006 (actual)
- First posted
- 2 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
Key exclusion criteria (8 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| dextromethorphandextromethorphan PO titrated to 480 mg/day x 5 weeks | Drug | – |
Primary outcome
Pain tolerance
Time frame: 6 week
1 secondary outcome
Pain threshold
Time frame: 6 week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jan 2017.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Margaret A Compton, RN, PhD principal investigator
UCLA School of Nursing
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing dextromethorphan in people with Opioid-induced Hyperalgesia, run by National Institute on Drug Abuse (NIDA) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 11 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pain tolerance (time frame: 6 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jan 2017; AzTrials last refreshed its copy on 6 Nov 2026.