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HIV InfectionsPhase 2NCT00000793

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

A Phase 2 study testing Mexiletine hydrochloride, Benztropine mesylate and Amitriptyline hydrochloride in people with HIV Infections and Peripheral Nervous System Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 37 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Mexiletine hydrochloride, Benztropine mesylate and Amitriptyline hydrochloride
How many people
240 participants
Where
37 sitesin 2 countries
Study dates
Start not givento Oct 1997
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Concurrent Medication:
  • Allowed:
  • Aspirin and acetaminophen.
  • Nonsteroidal anti-inflammatory agents.
  • Opiates.
  • Pyridoxine (only if accompanied by isoniazid).
Show all 23Show fewer
  • 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.

Who cannot join

  • 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.
Show all 44Show fewer
  • 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.

Trial locations and contacts

37 sites in 2 countries.

37 sites in 2 countries

United States36 sites

  • The Ponce de Leon Ctr. CRS

    Atlanta, Georgia

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80262

  • Johns Hopkins Adult AIDS CRS

    Baltimore, Maryland, 21287

  • Alabama Therapeutics CRS

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital ACTG CRS

    Boston, Massachusetts, 02114

  • Bmc Actg Crs

    Boston, Massachusetts, 02118

  • Beth Israel Deaconess Med. Ctr., ACTG CRS

    Boston, Massachusetts, 02215

  • Beth Israel Deaconess - East Campus A0102 CRS

    Boston, Massachusetts

  • SUNY - Buffalo, Erie County Medical Ctr.

    Buffalo, New York, 13210

  • Unc Aids Crs

    Chapel Hill, North Carolina, 275997215

  • Northwestern University CRS

    Chicago, Illinois, 60611

  • Cook County Hosp. CORE Ctr.

    Chicago, Illinois, 60612

  • Rush Univ. Med. Ctr. ACTG CRS

    Chicago, Illinois, 60612

  • Weiss Memorial Hosp.

    Chicago, Illinois, 60640

  • Univ. of Cincinnati CRS

    Cincinnati, Ohio, 452670405

  • Case CRS

    Cleveland, Ohio, 44106

  • Queens Med. Ctr.

    Honolulu, Hawaii, 96816

  • Univ. of Hawaii at Manoa, Leahi Hosp.

    Honolulu, Hawaii, 96816

  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic

    Indianapolis, Indiana, 462025250

  • Methodist Hosp. of Indiana

    Indianapolis, Indiana, 46202

  • Univ. of Iowa Healthcare, Div. of Infectious Diseases

    Iowa City, Iowa, 52242

  • UCLA CARE Center CRS

    Los Angeles, California, 90095

  • Univ. of Miami AIDS CRS

    Miami, Florida, 331361013

  • Hennepin County Med. Ctr., Div. of Infectious Diseases

    Minneapolis, Minnesota, 55415

  • University of Minnesota, ACTU

    Minneapolis, Minnesota, 55455

  • Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

    New Orleans, Louisiana

  • Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.

    Omaha, Nebraska, 681985130

  • Hosp. of the Univ. of Pennsylvania CRS

    Philadelphia, Pennsylvania, 19104

  • Univ. of Rochester ACTG CRS

    Rochester, New York, 14642

  • Ucsd, Avrc Crs

    San Diego, California, 921036325

  • Ucsf Aids Crs

    San Francisco, California

  • University of Washington AIDS CRS

    Seattle, Washington, 98104

  • St. Louis ConnectCare, Infectious Diseases Clinic

    St Louis, Missouri, 63112

  • Washington U CRS

    St Louis, Missouri

  • Harbor-UCLA Med. Ctr. CRS

    Torrance, California, 90502

  • Howard University Hosp., Div. of Infectious Diseases, ACTU

    Washington D.C., District of Columbia, 20059

Other trials in United States

Tanzania1 site

  • Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

    Mbeya

Other trials in Tanzania

About this study

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.

Read the 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.

Being tested
Mexiletine hydrochloride, Benztropine mesylate, Amitriptyline hydrochloride
Keywords
Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Peripheral Nervous System Diseases, Amitriptyline, Pain, Mexiletine, benzatropine methanesulfonate, Parasympatholytics
Medical subject headings
HIV Infections, Peripheral Nervous System Diseases, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Mexiletine hydrochlorideDrug

  • Benztropine mesylateDrug

  • Amitriptyline hydrochlorideDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study completionOct 1997

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Masking
Double blind
Enrolment
240 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00000793
Sponsor's protocol ID
ACTG 242
Other IDs
11219
Status last verified
Oct 2021
First submitted
2 Nov 1999
Last updated
29 Oct 2021
Results posted
No

Publications

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

    PubMed 11362419

  • 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.

    PubMed 9855523

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Mexiletine hydrochloride, Benztropine mesylate and Amitriptyline hydrochloride in people with HIV Infections and Peripheral Nervous System Disease, run by National Institute of Allergy and Infectious Diseases (NIAID) at 37 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in United States, Tanzania. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00000793, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2021.

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