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.

Condition	Treatment or Intervention
HIV Infections Peripheral Nervous System Diseases	Drug: Acetyl-L-carnitine

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).

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

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
• Onset or worsening of neuropathic symptoms must have been associated with the initiation or dose escalation of one or more dideoxynucleoside analogues
• 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
• 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.

California
      Univ of Texas, Southwestern Med Ctr, Sacramento,  California,  95814,  United States; Recruiting
      Stanford Univ, Stanford,  California,  94305,  United States; Recruiting
Illinois
      Cook County Hosp Core Ctr, Chicago,  Illinois,  60612,  United States; Recruiting
      Northwestern Univ, Chicago,  Illinois,  60611-3015,  United States; Recruiting
Maryland
      Johns Hopkins University, Baltimore,  Maryland,  21287-8106,  United States; Recruiting
Missouri
      Washington University (St. Louis), St. Louis,  Missouri,  63108-2138,  United States; Recruiting
New York
      Mount Sinai Med Ctr, New York,  New York,  10029,  United States; No longer recruiting
      The Cornell Clinical Trials Unit, New York,  New York,  10021,  United States; Not yet recruiting
      Beth Israel Med Ctr, New York,  New York,  10003,  United States; Recruiting
Texas
      Univ of Texas, Galveston, Galveston,  Texas,  77555-0435,  United States; Recruiting
Washington
      Univ of Washington (Seattle), Seattle,  Washington,  90033-1079,  United States; Recruiting

Study chairs or principal investigators

Victor Valcour, M.D.,  Study Chair,  University of Hawaii   
Russell Bartt, M.D.,  Study Chair,  Cook County Hospital and Rush-Presbyterian St. Luke's Medical Center   

Study ID Numbers:  ACTG A5157
Record last reviewed:  October 2004
Record first received:  December 3, 2002
ClinicalTrials.gov Identifier:  NCT00050271
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-11-08