Efficacy of Opioids and Mexiletine for the Treatment of Postamputation Pain - Full Text View

Sponsored by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00383682

Purpose

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.

Condition	Intervention	Phase
Amputation Chronic Pain	Drug: morphine and mexiletine	Phase II

Drug Information available for: Mexiletine Mexiletine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	Randomized, Placebo-Controlled, Double-Blind Cross-Over Trial of Opioids Versus Mexiletine in the Treatment of Postamputation Pain

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

Pain intensity (0-10 numerical rating scale)

Secondary Outcome Measures:

Pain relief (0-100%)
Functional activity (Multidimensional Pain Inventory activity and interference subscales

Estimated Enrollment:	60
Study Start Date:	July 1997
Estimated Study Completion Date:	April 2003

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.

Eligibility

Ages Eligible for Study:	18 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00383682

Locations

United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287

Sponsors and Collaborators

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

Investigators

Principal Investigator:

Srinivasa N Raja, M.D.

Johns Hopkins University

More Information

No publications provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

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.

Study ID Numbers:	P01HD33990, Project 2, P01HD33990
Study First Received:	September 29, 2006
Last Updated:	September 29, 2006
ClinicalTrials.gov Identifier:	NCT00383682 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

postamputation pain
phantom pain
stump pain

neuroma pain
opioid
mexiletine

Study placed in the following topic categories:

Morphine
Central Nervous System Depressants
Mexiletine
Pain
Peripheral Nervous System Agents
Cardiovascular Agents

Anti-Arrhythmia Agents
Analgesics
Phantom Limb
Neuroma
Analgesics, Opioid

Additional relevant MeSH terms:

Sensory System Agents
Therapeutic Uses
Physiological Effects of Drugs
Central Nervous System Depressants
Mexiletine
Peripheral Nervous System Agents

Analgesics
Cardiovascular Agents
Anti-Arrhythmia Agents
Central Nervous System Agents
Pharmacologic Actions
Analgesics, Opioid

ClinicalTrials.gov processed this record on May 07, 2009