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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000793
• Other study ID #: ACTG 242
• Secondary ID: 11219
• Status: Completed
• Phase: Phase 2
• Est. completion date: October 1997

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: October 1997
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections
• Nervous System Diseases
• Peripheral Nervous System Disease
• Peripheral Nervous System Diseases

Intervention

Drug:
• Mexiletine hydrochloride

• Benztropine mesylate

• Amitriptyline hydrochloride

Locations

Country	Name	City	State
Tanzania	Mbeya Med. Research Program, Mbeya Referral Hosp. CRS	Mbeya
United States	The Ponce de Leon Ctr. CRS	Atlanta	Georgia
United States	University of Colorado Hospital CRS	Aurora	Colorado
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Alabama Therapeutics CRS	Birmingham	Alabama
United States	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts
United States	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts
United States	Bmc Actg Crs	Boston	Massachusetts
United States	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts
United States	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Cook County Hosp. CORE Ctr.	Chicago	Illinois
United States	Northwestern University CRS	Chicago	Illinois
United States	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois
United States	Weiss Memorial Hosp.	Chicago	Illinois
United States	Univ. of Cincinnati CRS	Cincinnati	Ohio
United States	Case CRS	Cleveland	Ohio
United States	Queens Med. Ctr.	Honolulu	Hawaii
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
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	UCLA CARE Center CRS	Los Angeles	California
United States	Univ. of Miami AIDS CRS	Miami	Florida
United States	Hennepin County Med. Ctr., Div. of Infectious Diseases	Minneapolis	Minnesota
United States	University of Minnesota, ACTU	Minneapolis	Minnesota
United States	Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU	New Orleans	Louisiana
United States	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsd, Avrc Crs	San Diego	California
United States	Ucsf Aids Crs	San Francisco	California
United States	University of Washington AIDS CRS	Seattle	Washington
United States	Harbor-UCLA Med. Ctr. CRS	Torrance	California
United States	Howard University Hosp., Div. of Infectious Diseases, ACTU	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Tanzania, 

References & Publications (2)

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. — View Citation

Lein B. Potential therapy for painful neuropathy. PI Perspect. 1995 May;(no 16):11. — View Citation