A Phase II/III Double-Blind Study of Amitriptyline and Mexiletine for Painful Neuropathy in HIV Infection
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections; Peripheral Nervous System Disease
Intervention: Mexiletine hydrochloride (Drug); Benztropine mesylate (Drug); Amitriptyline hydrochloride (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
K Kieburtz, Study Chair
D Simpson, Study Chair
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.
Clinical Details
Official title: A Phase II/III Double-Blind Study of Amitriptyline and Mexiletine for Painful Neuropathy in HIV Infection
Study design: Treatment, Double-Blind, Safety Study
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
VA Hosp at San Diego / Pediatrics, San Diego, California 92161, United States
San Francisco Gen Hosp, San Francisco, California 941102859, United States
San Francisco AIDS Clinic / San Francisco Gen Hosp, San Francisco, California 941102859, United States
Summitt Med Ctr / San Francisco Gen Hosp, Oakland, California 94609, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
Harbor UCLA Med Ctr, Torrance, California 90502, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Kaiser Permanente Franklin Med Ctr, Denver, Colorado 80262, United States
Rose Med Ctr, Denver, Colorado 80262, United States
Yale Univ / New Haven, New Haven, Connecticut 065102483, United States
Howard Univ, Washington, District of Columbia 20059, United States
Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Emory Univ, Atlanta, Georgia 30308, United States
Queens Med Ctr, Honolulu, Hawaii 96816, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Illinois Masonic Med Ctr, Chicago, Illinois 606575147, United States
Louis A Weiss Memorial Hosp, Chicago, Illinois 60640, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Univ of Iowa Hosp and Clinic, Iowa City, Iowa 52242, United States
Charity Hosp / Tulane Univ Med School, New Orleans, Louisiana 70112, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
St Paul Ramsey Med Ctr, St. Paul, Minnesota 55101, United States
Hennepin County Med Clinic, Minneapolis, Minnesota 55415, United States
St Louis Regional Hosp / St Louis Regional Med Ctr, St. Louis, Missouri 63112, United States
Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
SUNY / State Univ of New York, Syracuse, New York 13210, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Jack Weiler Hosp / Bronx Municipal Hosp, Bronx, New York 10465, United States
Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx, New York 10461, United States
Montefiore Med Ctr / Bronx Municipal Hosp, Bronx, New York 10467, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
North Central Bronx Hosp / Bronx Municipal Hosp, Bronx, New York 10467, United States
Comprehensive Health Care Ctr / Bronx Municipal Hosp, Bronx, New York 10461, United States
Columbia Presbyterian Med Ctr, New York, New York 100323784, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Case Western Reserve Univ, Cleveland, Ohio 44106, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Univ of Pennsylvania at Philadelphia, Philadelphia, Pennsylvania 19104, United States
Thomas Jefferson Univ Hosp, Philadelphia, Pennsylvania 191075098, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Meharry Med College, Nashville, Tennessee 37203, United States
Univ of Texas Galveston, Galveston, Texas 775550435, United States
Univ of Washington, Seattle, Washington 981224304, United States
Additional Information
Related publications: Lein B. Potential therapy for painful neuropathy. PI Perspect. 1995 May;(no 16):11. No abstract available. 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.
Last updated: June 23, 2005
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