Efficacy of Opioids and Mexiletine for the Treatment of Postamputation Pain

Chronic Pain Clinical Trial

Official title:

Randomized, Placebo-Controlled, Double-Blind Cross-Over Trial of Opioids Versus Mexiletine in the Treatment of Postamputation Pain

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00383682
• Other study ID #: P01HD033990
• Secondary ID: Project 2, P01HD
• Status: Completed
• Phase: Phase 2
• First received: September 29, 2006
• Last updated: September 29, 2006
• Start date: July 1997
• Est. completion date: April 2003

Study information

• Verified date: September 2006
• Source: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical 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.

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.

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:

1. 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.

2. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: April 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amputation
• Chronic Pain

Intervention

Drug:
• morphine and mexiletine

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pain intensity (0-10 numerical rating scale)
Secondary	Pain relief (0-100%)
Secondary	Functional activity (Multidimensional Pain Inventory activity and interference subscales