A Phase II/III Double-Blind Study of Amitriptyline and Mexiletine for Painful Neuropathy in HIV Infection
NCT ID: NCT00000793
Last Updated: 2021-10-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
240 participants
INTERVENTIONAL
1997-10-31
Brief Summary
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No large-scale controlled clinical trials of symptomatic therapy for painful HIV-related neuropathy have been attempted. Both amitriptyline and mexiletine have been useful in the management of painful neuropathies; however, both are associated with certain toxicities. In this comparative study of amitriptyline and mexiletine, benztropine mesylate also will be included as an active placebo to mimic the side effects of the study drugs.
Detailed Description
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Patients are randomized to receive amitriptyline, mexiletine, or benztropine mesylate as an active placebo to mimic the mild side effects associated with both amitriptyline and mexiletine. Doses are gradually increased over 4 weeks until a minimum effective dose or MTD is reached, then patients are treated for at least 4 additional weeks at the final dose before gradually tapering off. Neurologic exams are performed at screening and at the end of treatment. Intensity of pain is rated twice daily by the patient. Patients are followed at Weeks 2, 4, and 8, and at 10 days after completely tapering off of drug.
PER 3/16/95 AMENDMENT: Patients with no pain relief 14 days after initiation of study therapy may have dose doubled or increased to maximum allowable dose, whichever is lower. Then if no improvement occurs within 14 days after dose increase, patients have the option of discontinuing study medication.
Conditions
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Keywords
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Study Design
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TREATMENT
DOUBLE
Interventions
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Mexiletine hydrochloride
Benztropine mesylate
Amitriptyline hydrochloride
Eligibility Criteria
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Inclusion Criteria
Allowed:
* Aspirin and acetaminophen.
* Nonsteroidal anti-inflammatory agents.
* Opiates.
* Pyridoxine (only if accompanied by isoniazid).
* ddI, ddC, d4T, and 3TC if on a stable dose.
* AZT.
* Cimetidine if on a stable dose.
NOTE:
* Per 3/16/95 amendment, Lactaid may be taken by lactose-intolerant patients for effects of lactose in placebo capsules.
Concurrent Treatment:
Allowed:
* Acupuncture.
Patients must have:
* Documented HIV infection.
* Painful peripheral neuropathy.
NOTE:
* Patients in ACTG blinded studies of dideoxynucleosides such as ddI, ddC, and d4T are encouraged to enroll in this study.
Prior Medication:
Allowed:
* Prior ddI, ddC, d4T, or 3TC, if on a stable dose for at least 8 weeks prior to study entry.
* Prior cimetidine if on a stable dose for at least 2 weeks prior to study entry.
Exclusion Criteria
Patients with the following symptoms or conditions are excluded:
* Diabetes mellitus.
* Neurological disease of sufficient severity to confound the evaluation of peripheral neuropathy, such as myelopathy without neuropathy. (NOTE: Patients with both myelopathy AND painful peripheral neuropathy are eligible.)
* Electrocardiogram (EKG) indicating malignant arrhythmia or cardiac conduction disturbances (such as second or third degree AV block, anterior hemi-block, or prolonged QT interval).
* Suicidal thoughts of sufficient severity to require treatment with antidepressant medication.
Concurrent Medication:
Excluded:
* Phenytoin or carbamazepine (unless on stable dose for 8 weeks prior to study entry).
* Capsaicin.
* Any MAO inhibitor antidepressants, any tricyclic or tetracyclic antidepressants, certain serotonin re-uptake inhibitors (fluoxetine, paroxetine, and venlafaxine), or mexiletine (except as dispensed for this study).
* Disopyramide.
* Procainamide.
* Quinidine.
* Tocainide.
* Flecainide acetate.
* Encainide.
* Lidocaine.
* Cisplatin.
* Vincristine.
* Chloramphenicol, disulfiram, ethionamide glutethimide, gold, hydralazine, iodoquinol, metronidazole, nitrofurantoin, or ribavirin (only in patients in whom the onset or clear worsening of painful peripheral neuropathy was attributed to previously taking these drugs).
* Any investigational drugs other than 3TC (except with permission of the protocol team).
* Terfenadine (if concurrent with ketoconazole).
Patients with the following prior conditions are excluded:
* Documented history of cardiac disease.
* History of allergy to, or intolerance of, tricyclic antidepressants, mexiletine, or benztropine.
Prior Medication:
Excluded:
* Prior disopyramide.
* Prior procainamide.
* Prior quinidine.
* Prior tocainide.
* Prior flecainide acetate.
* Prior encainide.
* Prior lidocaine.
* Cisplatin or vincristine within 8 weeks prior to study entry.
* Chloramphenicol, disulfiram, ethionamide glutethimide, gold, hydralazine, iodoquinol, metronidazole, nitrofurantoin, or ribavirin within 8 weeks prior to study entry (only in patients in whom the onset or clear worsening of painful peripheral neuropathy was attributed to taking these drugs).
* Any MAO inhibitor antidepressants, any tricyclic or tetracyclic antidepressants, certain serotonin re-uptake inhibitors (fluoxetine, paroxetine, and venlafaxine), or mexiletine, within 4 weeks prior to study entry.
* More than 50 percent change in the weekly dosage of any pain control medications within 2 weeks prior to study entry.
Per 3/16/95 amendment:
* ddI, ddC, d4T, or 3TC within 8 weeks prior to study entry ONLY IF dideoxynucleoside dosing was suspended or permanently discontinued.
Risk Behavior:
Excluded:
* Active drug or alcohol abuse.
18 Years
ALL
No
Sponsors
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Boehringer Ingelheim
INDUSTRY
National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Responsible Party
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Principal Investigators
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K Kieburtz
Role: STUDY_CHAIR
D Simpson
Role: STUDY_CHAIR
Locations
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Alabama Therapeutics CRS
Birmingham, Alabama, United States
UCLA CARE Center CRS
Los Angeles, California, United States
Ucsd, Avrc Crs
San Diego, California, United States
Ucsf Aids Crs
San Francisco, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States
University of Colorado Hospital CRS
Aurora, Colorado, United States
Howard University Hosp., Div. of Infectious Diseases, ACTU
Washington D.C., District of Columbia, United States
Univ. of Miami AIDS CRS
Miami, Florida, United States
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States
Queens Med. Ctr.
Honolulu, Hawaii, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States
Northwestern University CRS
Chicago, Illinois, United States
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States
Weiss Memorial Hosp.
Chicago, Illinois, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, United States
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States
Bmc Actg Crs
Boston, Massachusetts, United States
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States
Hennepin County Med. Ctr., Div. of Infectious Diseases
Minneapolis, Minnesota, United States
University of Minnesota, ACTU
Minneapolis, Minnesota, United States
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St Louis, Missouri, United States
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
Omaha, Nebraska, United States
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States
Univ. of Rochester ACTG CRS
Rochester, New York, United States
Unc Aids Crs
Chapel Hill, North Carolina, United States
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States
Case CRS
Cleveland, Ohio, United States
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States
University of Washington AIDS CRS
Seattle, Washington, United States
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
Mbeya, , Tanzania
Countries
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References
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Lein B. Potential therapy for painful neuropathy. PI Perspect. 1995 May;(no 16):11.
Kieburtz K, Simpson D, Yiannoutsos C, Max MB, Hall CD, Ellis RJ, Marra CM, McKendall R, Singer E, Dal Pan GJ, Clifford DB, Tucker T, Cohen B. A randomized trial of amitriptyline and mexiletine for painful neuropathy in HIV infection. AIDS Clinical Trial Group 242 Protocol Team. Neurology. 1998 Dec;51(6):1682-8. doi: 10.1212/wnl.51.6.1682.
Other Identifiers
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11219
Identifier Type: REGISTRY
Identifier Source: secondary_id
ACTG 242
Identifier Type: -
Identifier Source: org_study_id