AmputationPhase 2NCT00383682
Efficacy of Opioids and Mexiletine for the Treatment of Postamputation Pain
A Phase 2 study testing morphine and mexiletine in people with Amputation and Chronic Pain, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
Persistent pain occurs in 50-85 percent of patients who experience the amputation of an extremity. This study will compare the effectiveness of morphine and mexiletine to placebo in the treatment of postamputation pain. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Amputation, Chronic Pain
- What is being tested?
- morphine and mexiletine
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 1997to Apr 2003
- Phase
- Phase 2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults (18 years or older) of both sexes and all races with persistent phantom and or stump pain for 6 months or longer following an amputation will be eligible for enrollment in the study.
Who cannot join
- 1) age less than 18 or over 85 years, 2) history of allergic reaction to the study drugs, i.e., morphine and mexiletine, 3) cardiac conduction defects such as second degree or complete heart block, or a myocardial infarction in the last 3 months, 4) severe pulmonary disease, 5) current history of alcohol or substance abuse, 6) seizures, dementia or encephalopathy, 7) pregnancy and nursing mothers, 8) chronic hepatic disease or hepatic failure, 9) hematological disease associated with leukopenia and/or thrombocytopenia, and 10) other terminal illness with a life expectancy of less than 6 months. 11) Finally, to avoid a bias in patient selection, patients who failed to achieve clinically significant pain relief to a previous optimal trial with morphine and/or mexiletine will be excluded. An optimal trial will be defined as minimum of 3 week trial with either agent using a drug titration paradigm where the dose of the drugs were increased at intervals of one week or less.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Placebo-Controlled, Double-Blind Cross-Over Trial of Opioids Versus Mexiletine in the Treatment of Postamputation Pain
Persistent pain occurs in 50-85 percent of patients who experience the amputation of an extremity. This study will compare the effectiveness of morphine and mexiletine to placebo in the treatment of postamputation pain.
It is hypothesized that the effects of opioids and mexiletine on behavior and mental functioning in patients with postamputation pain are unlikely to be significant barriers to the clinical use of the drugs.
Read the detailed description
The long-term objective of this research is to develop better clinical strategies for alleviating pain resulting from amputation of extremities. Amputation is the most radical form of nerve injury. The two major types of postamputation painful sequela are phantom pain and stump pain. Phantom pain has been defined as painful sensation perceived in the missing body part, or portion thereof (Merskey and Bogduk,1994). Phantom pain is the most distressing, and often difficult to treat, chronic neuropathic pain syndrome that results from direct injury to the peripheral or central nervous system. Recent epidemiological studies indicate that 50-85% of patients experience persistent pain following amputations. This controlled clinical trial will examine the role of opioid analgesics and local anesthetics in the treatment of phantom and associated stump pain resulting from amputations. Specifically, our objectives are to answer the following questions:
- Does therapy with opioids and mexiletine result in better management of postamputation pain than treatment with placebo? Using a randomized, blinded, crossover clinical trial, the effectiveness of therapy with the opioid, morphine, and the oral local anesthetic, mexiletine, will be compared with placebo in the management of phantom and associated stump pain following amputations. The effectiveness of the treatment regimens will be judged by improvements in: a) The intensity of ongoing, stimulus-independent pain using established pain intensity and pain relief scales, b) Stimulus-evoked pain using quantitative sensory tests, and c) Impairment of function using established measures.
- What are the relative effects of opioids and mexiletine on affective and cognitive function in patients with amputated extremities? Using established tests of neuropsychological function, mood, and psychosocial and physical impairment, affective and cognitive changes associated with the opioid and mexiletine therapies will be quantified and compared with changes associated with placebo treatment. These studies will help determine if the effects of opioids and mexiletine on affect and cognition are likely to limit the usefulness of the medications in the treatment of pain following amputations.
- Conditions
- Amputation, Chronic Pain
- Being tested
- morphine and mexiletine
- Keywords
- postamputation pain, phantom pain, stump pain, neuroma pain, opioid, mexiletine
- Medical subject headings
- Chronic Pain, Phantom Limb
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
morphine and mexiletineDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Pain intensity (0-10 numerical rating scale)
Secondary outcomes (2)
Pain relief (0-100%)
Functional activity (Multidimensional Pain Inventory activity and interference subscales
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2006 (estimated)
- Study startJul 1997
- Study completionApr 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AmputationStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 60 participants
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Investigators
- Srinivasa N Raja, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00383682
- Sponsor's protocol ID
- P01HD033990
- Other IDs
- Project 2, P01HD33990
- Status last verified
- Sep 2006
- First submitted
- 29 Sep 2006
- Last updated
- 3 Oct 2006
- Results posted
- No
Publications
Wu CL, Agarwal S, Tella PK, Klick B, Clark MR, Haythornthwaite JA, Max MB, Raja SN. Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial. Anesthesiology. 2008 Aug;109(2):289-96. doi: 10.1097/ALN.0b013e31817f4523.
PubMed 18648238
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2006. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Placebo-Controlled, Double-Blind Cross-Over Trial of Opioids Versus Mexiletine in the Treatment of Postamputation Pain
- ClinicalTrials.gov ID
- NCT00383682
- Acronym / sponsor ID
- P01HD033990
- Conditions
- Amputation, Chronic Pain
- Keywords
- postamputation pain, phantom pain, stump pain, neuroma pain, opioid, mexiletine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Jul 1997
- Study completion
- Apr 2003
- First posted
- 3 Oct 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.
Persistent pain occurs in 50-85 percent of patients who experience the amputation of an extremity. This study will compare the effectiveness of morphine and mexiletine to placebo in the treatment of postamputation pain.
It is hypothesized that the effects of opioids and mexiletine on behavior and mental functioning in patients with postamputation pain are unlikely to be significant barriers to the clinical use of the drugs.
Detailed description
The long-term objective of this research is to develop better clinical strategies for alleviating pain resulting from amputation of extremities. Amputation is the most radical form of nerve injury. The two major types of postamputation painful sequela are phantom pain and stump pain. Phantom pain has been defined as painful sensation perceived in the missing body part, or portion thereof (Merskey and Bogduk,1994). Phantom pain is the most distressing, and often difficult to treat, chronic neuropathic pain syndrome that results from direct injury to the peripheral or central nervous system. Recent epidemiological studies indicate that 50-85% of patients experience persistent pain following amputations. This controlled clinical trial will examine the role of opioid analgesics and local anesthetics in the treatment of phantom and associated stump pain resulting from amputations. Specifically, our objectives are to answer the following questions:
- Does therapy with opioids and mexiletine result in better management of postamputation pain than treatment with placebo? Using a randomized, blinded, crossover clinical trial, the effectiveness of therapy with the opioid, morphine, and the oral local anesthetic, mexiletine, will be compared with placebo in the management of phantom and associated stump pain following amputations. The effectiveness of the treatment regimens will be judged by improvements in: a) The intensity of ongoing, stimulus-independent pain using established pain intensity and pain relief scales, b) Stimulus-evoked pain using quantitative sensory tests, and c) Impairment of function using established measures.
- What are the relative effects of opioids and mexiletine on affective and cognitive function in patients with amputated extremities? Using established tests of neuropsychological function, mood, and psychosocial and physical impairment, affective and cognitive changes associated with the opioid and mexiletine therapies will be quantified and compared with changes associated with placebo treatment. These studies will help determine if the effects of opioids and mexiletine on affect and cognition are likely to limit the usefulness of the medications in the treatment of pain following amputations.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adults (18 years or older) of both sexes and all races with persistent phantom and or stump pain for 6 months or longer following an amputation will be eligible for enrollment in the study.
Key exclusion criteria (1 listed)
- 1) age less than 18 or over 85 years, 2) history of allergic reaction to the study drugs, i.e., morphine and mexiletine, 3) cardiac conduction defects such as second degree or complete heart block, or a myocardial infarction in the last 3 months, 4) severe pulmonary disease, 5) current history of alcohol or substance abuse, 6) seizures, dementia or encephalopathy, 7) pregnancy and nursing mothers, 8) chronic hepatic disease or hepatic failure, 9) hematological disease associated with leukopenia and/or thrombocytopenia, and 10) other terminal illness with a life expectancy of less than 6 months. 11) Finally, to avoid a bias in patient selection, patients who failed to achieve clinically significant pain relief to a previous optimal trial with morphine and/or mexiletine will be excluded. An optimal trial will be defined as minimum of 3 week trial with either agent using a drug titration paradigm where the dose of the drugs were increased at intervals of one week or less.
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 |
|---|---|---|
| morphine and mexiletine | Drug | – |
Primary outcome
Pain intensity (0-10 numerical rating scale)
2 secondary outcomes
Pain relief (0-100%)
Functional activity (Multidimensional Pain Inventory activity and interference subscales
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2006.
- Derived from this study: PubMed 18648238Wu CL, Agarwal S, Tella PK, Klick B, Clark MR, Haythornthwaite JA, Max MB, Raja SN. Morphine versus mexiletine for treatment of postamputation pain: a randomized, placebo-controlled, crossover trial. Anesthesiology. 2008 Aug;109(2):289-96. doi: 10.1097/ALN.0b013e31817f4523.
Related trials for Amputation
RecruitingObservational study
Cryo NerVe Block Extremity AmputatioN RegIStry for Post Operative and pHantom Limb Pain
Amputation, Amputation of Lower Limb
RecruitingObservational study
CNS Changes Following Upper Limb Loss
Amputation, Congenital, Upper Limb; Amelia
Recruiting
Hand Prosthesis Usability and Performance
Amputation
Recruiting
E-Socket, Diagnostic Monitoring
Trans-Tibial Amputation
RecruitingObservational study
Early Postoperative Pain Following a Limb Amputation
Amputation, Surgical, Pain Management
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.
Srinivasa N Raja, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing morphine and mexiletine in people with Amputation and Chronic Pain, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 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 1 inclusion and 1 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: finished, as of the sponsor's last update on 3 Oct 2006. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 intensity (0-10 numerical rating scale). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00383682, which also lists 1 linked publication.
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 3 Oct 2006.