Safety and Efficacy Study of Ethosuximide for the Treatment of Complex Regional Pain Syndrome (CRPS)

A Single Centre. Parallel-Group, Double-Blinded, Randomized, Placebo-Controlled Pilot Clinical Trial on Ethosuximide for the Treatment of Complex Regional Pain Syndrome (CRPS)

Pain remains the most debilitating symptom for adult patients suffering from complex regional pain syndrome (CRPS). Most CRPS patients gain little to no relief from current painkillers. The purpose of this study is to evaluate the efficacy and safety of ethosuximide in search of much-needed adjunctive therapy to relieve the pain and suffering associated with CRPS.

Study Overview

• Status: Terminated
• Conditions: Complex Regional Pain Syndromes
• Intervention / Treatment: Drug: Placebo; Drug: Ethosuximide

Detailed Description

This is a single centre, parallel-group, double-blind, randomized, placebo-controlled pilot clinical trial for adults suffering from complex regional pain syndrome (CRPS).

Twelve (12) subjects diagnosed with CRPS will be enrolled and randomized to receive orally, either ethosuximide or placebo. If the maximum trial medication dosage (1500mg) is reached, the subject will be in the study for a maximum of 10 weeks from screening (Clinic Visit 1) to the end of the drug cessation period. The minimum period a subject could complete the study would be 4 weeks presuming they were not previously on any disallowed drugs and only found the 500mg dose tolerable.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3G 1A4
      • McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female, age ≥18 years old;
• Diagnosis of Complex Regional Pain Syndrome (CRPS) using International Association for the Study of Pain criteria >6 months;
• Normal liver function (AST level <3x normal level);
• Normal kidney function (serum creatinine <133µmol/L);
• Full blood count, haematocrit >38%;
• Willing and able to give informed consent and of completing study questionnaires;
• Stable (no change in past two months) but suboptimal pain pharmacotherapy (i.e. additional pain control felt by patient and physician to be necessary);
• Able to attend research centre according to the visit schedule;
• Women of child-bearing potential must be using a reliable form of contraception i.e. oral contraceptives, a barrier method (condom or diaphragm), intra-uterine device or abstinence.

Exclusion Criteria:

• Optimal response to opioids, antidepressants, anticonvulsants or anti- inflammatory medications;
• Any history or indication of kidney or liver disease;
• Any history of alcohol abuse;
• Presence of diabetes;
• Subjects taking other anti-epileptic drugs, including gabapentin, pregabalin, topiramate, phenytoin, carbamazepine, and oxcarbazepine;
• Pregnancy (a serum bHCG pregnancy test will be performed as part of the initial blood panel);
• Known or suspected allergy to succinimides, ethosuximide, methsuximide (Celontin®), phensuximide;
• Any history of mental illness or disorder, which in the investigators opinion, interferes with the subjects ability to accurately report treatment response;
• Participation in other clinical trial in the 30 days prior to enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 2	Drug: Ethosuximide; 500-1500mg/day over a 1-5 week dose titration period until maximal tolerated dose (MTD) attained, followed by 1 week MTD plateau period.; Other Names: Zarontin
PLACEBO_COMPARATOR: 1	Drug: Placebo; 250mg matching placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (500mg-1500mg per day) and Safety profile	Primary outcomes will consist of the dose attained during the study and the safety (adverse event) profile. Maximum timeframe on study drug is 6 weeks. Adverse events will be collected up to one month after the trial period ends.	up to 10 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity Scores on the Visual Analogue Scale (VAS)	Pain Intensity captured on Day 1 (First study visit post-disallowed drug cessation period) and 7 days after maximal-tolerated dose attained (Final Study Visit)	up to 7 weeks
Pain Intensity Scores on the Numerical Rating Scale (NRS)	Pain Intensity using the Numerical Rating Scale will be captured by telephone every week during dose titration period (Days 3 and 6).	up to 5 weeks
Neuropathic Pain Symptom Inventory (NPSI)	Day 1 (First study visit post-disallowed drug cessation period) and 7 days after maximal-tolerated dose attained (Final Study Visit)	up to 7 weeks
Short Form 12v2 (SF-12v2)	Quality of Life measured on Day 1 (First study visit post-disallowed drug cessation period) and 7 days after maximal-tolerated dose attained (Final Study Visit)	up to 7 weeks
Short Form McGill Pain Questionnaire (SF-MPQ)	Day 1 (First study visit post-disallowed drug cessation period) and 7 days after maximal-tolerated dose attained (Final Study Visit)	up to 7 weeks

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: McGill University
• Investigators: Principal Investigator: Mark A Ware, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (ACTUAL): July 1, 2010
• Study Completion (ACTUAL): July 1, 2010

Study Registration Dates

• First Submitted: May 29, 2008
• First Submitted That Met QC Criteria: May 29, 2008
• First Posted (ESTIMATE): June 3, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): May 13, 2011
• Last Update Submitted That Met QC Criteria: May 11, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Chronic Pain; Complex Regional Pain Syndrome; RSD; Anticonvulsant; Ethosuximide; Reflex Sympathetic Dystrophy; Zarontin
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Disease; Neuromuscular Diseases; Peripheral Nervous System Diseases; Autonomic Nervous System Diseases; Syndrome; Complex Regional Pain Syndromes; Reflex Sympathetic Dystrophy; Somatoform Disorders; Anticonvulsants; Ethosuximide
• Other Study ID Numbers: GEN#07-062