A Phase II/III Double-Blind Study of Amitriptyline and Mexiletine for Painful Neuropathy in HIV Infection

This study has been completed.
Sponsor:
Collaborator:
Boehringer Ingelheim
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000793
First received: November 2, 1999
Last updated: April 2, 2012
Last verified: April 2012
  Purpose

To assess the efficacy, safety, and tolerability of amitriptyline hydrochloride versus mexiletine hydrochloride in reducing pain intensity in patients with HIV-related painful peripheral neuropathy.

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.


Condition Intervention Phase
HIV Infections
Peripheral Nervous System Disease
Drug: Mexiletine hydrochloride
Drug: Benztropine mesylate
Drug: Amitriptyline hydrochloride
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase II/III Double-Blind Study of Amitriptyline and Mexiletine for Painful Neuropathy in HIV Infection

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 240
Study Completion Date: October 1997
Detailed Description:

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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

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

Co-existing Condition:

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000793

  Hide Study Locations
Locations
United States, Alabama
Alabama Therapeutics CRS
Birmingham, Alabama, United States, 35294
United States, California
UCLA CARE Center CRS
Los Angeles, California, United States, 90095
Ucsd, Avrc Crs
San Diego, California, United States, 921036325
Ucsf Aids Crs
San Francisco, California, United States
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80262
United States, District of Columbia
Howard University Hosp., Div. of Infectious Diseases, ACTU
Washington, District of Columbia, United States, 20059
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 331361013
United States, Georgia
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, United States
United States, Hawaii
Queens Med. Ctr.
Honolulu, Hawaii, United States, 96816
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, United States, 96816
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60612
Cook County Hosp. CORE Ctr.
Chicago, Illinois, United States, 60612
Weiss Memorial Hosp.
Chicago, Illinois, United States, 60640
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 462025250
Methodist Hosp. of Indiana
Indianapolis, Indiana, United States, 46202
United States, Iowa
Univ. of Iowa Healthcare, Div. of Infectious Diseases
Iowa City, Iowa, United States, 52242
United States, Louisiana
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med. Ctr., ACTG CRS
Boston, Massachusetts, United States, 02215
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
Beth Israel Deaconess - East Campus A0102 CRS
Boston, Massachusetts, United States
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
Hennepin County Med. Ctr., Div. of Infectious Diseases
Minneapolis, Minnesota, United States, 55415
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States, 63112
Washington U CRS
St. Louis, Missouri, United States
United States, Nebraska
Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
Omaha, Nebraska, United States, 681985130
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 13210
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 452670405
Case CRS
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, United States, 19104
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104
Tanzania
Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
Mbeya, Tanzania
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: K Kieburtz
Study Chair: D Simpson
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000793     History of Changes
Other Study ID Numbers: ACTG 242, 11219
Study First Received: November 2, 1999
Last Updated: April 2, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Peripheral Nervous System Diseases
Amitriptyline
Pain
Mexiletine
benzatropine methanesulfonate
Parasympatholytics

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Nervous System Diseases
Peripheral Nervous System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Neuromuscular Diseases
Amitriptyline
Amitriptyline, perphenazine drug combination
Benztropine
Mexiletine
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic Uptake Inhibitors

ClinicalTrials.gov processed this record on April 23, 2014