Acetyl-L-Carnitine for the Treatment of NRTI-Associated Peripheral Neuropathy

National Institute of Allergy and Infectious Diseases (NIAID)

Status

Completed

Conditions

Peripheral Nervous System Diseases

HIV Infections

Treatments

Drug: Acetyl-L-carnitine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00050271

A5157

ACTG A5157

10004 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to determine if acetyl-L-carnitine (ALC) reduces pain, numbness, and tingling in the feet and legs of patients with nucleoside reverse transcriptase inhibitor (NRTI)-associated peripheral neuropathy. Another purpose is to determine if ALC is safe and tolerable in HIV patients who have taken certain anti-HIV drugs.

Full description

Distal symmetric peripheral neuropathy (DSPN) is the most frequent neurologic complication of HIV infection and its treatments. NRTIs, particularly dideoxy-NRTIs, represent a significant risk factor for developing neuropathy. To date, there are no effective treatments for DSPN. Studies of nonneuronal tissues indicate a beneficial effect of ALC in HIV-1 seropositive individuals, but the role of ALC levels in patients with DSPN is unclear. Despite conflicting data, carnitine and its derivatives are still commonly used.

Patients will have a screening visit and visits at entry and Weeks 6, 12, 18, and 24. Patients are required to fast (no food or drink except water) for 4-12 hours for the screening visit, entry visit, and at Weeks 12 and 24. Targeted physical examinations, blood chemistries, liver function tests, HIV-1 RNA, CD4/CD8 cell counts, hematology, and lactate assessments will be done. Patients will also have a small skin biopsy at entry and Week 24. Patients will begin with 1 tablet of ALC twice daily and escalate dosage to a target dose of 3 tablets daily. They will remain on the 3-tablet dose or a maximum tolerated dose for the duration of the study (24 weeks).

Enrollment

27 patients

Sex

All

Ages

13+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

HIV-1 infection
Viral load <= 10,000 copies/ml within 60 days of entry
On stable antiretroviral medication for 8 weeks prior to entry and plan on staying on current regimen for the duration of the study
Currently taking at least one dideoxynucleoside analogue. Patients discontinuing their dideoxynucleoside analogues or changing their antiretroviral regimen after entry will remain on study drug and continue with the study requirements and evaluation visits.
No significant systemic antiretroviral toxicity
Evidence of predominantly sensory neuropathy, as determined from an examination by a neurologist
Ongoing neuropathy of any duration
Negative pregnancy test performed at screening and within 24 hours of study entry
Agree not to become pregnant or to impregnate; agree to use acceptable methods of contraception

Exclusion criteria

ALC or similar drug within 90 days of entry
Active AIDS-defining opportunistic infection (OI) or OI-defining condition within 30 days prior to entry
Any condition or history of any condition, other than that related to HIV infection or antiretroviral therapy, that would add confusion to the diagnosis of dideoxynucleoside analogue-associated DSPN
Pregnancy or breast-feeding
Active malignancy
Seizure disorder or history of seizure within 90 days of entry
Current or history of bipolar disorder
Certain drugs within 30 days of study entry
Addition of certain pain medication during the 60 days prior to study entry
Allergy/sensitivity to study drug or its formulations
Any condition that, in the opinion of the site investigator, would interfere with the study requirements
Myelopathy
Use of investigational agents that are not FDA-approved within 30 days of study entry, except when approved by the study chair. Investigational antiretroviral drugs available through expanded access or through AACTG trials will be allowed if they do not conflict with study criteria.