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

An Open-Label, Dose-Escalation Pilot Study of Acetyl-L-Carnitine for the Treatment of Dideoxynucleoside-Associated Distal Symmetric Peripheral Neuropathy

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Peripheral Nervous System Diseases
• Intervention / Treatment: Drug: Acetyl-L-carnitine

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00936-5067
    • Puerto Rico-AIDS CRS
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford CRS
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • The Ponce de Leon Ctr. CRS
  • Hawaii
    • Honolulu, Hawaii, United States
      • Univ. of Hawaii at Manoa, Leahi Hosp.
  • Illinois
    • Chicago, Illinois, United States, 60611-3015
      • Northwestern University CRS
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp. CORE Ctr.
  • Maryland
    • Baltimore, Maryland, United States, 21287-8106
      • Johns Hopkins Adult AIDS CRS
  • Missouri
    • Saint Louis, Missouri, United States, 63108-2138
      • Washington U CRS
  • New York
    • New York, New York, United States, 10003
      • Beth Israel Med. Ctr., ACTU
    • New York, New York, United States
      • Weill Med. College of Cornell Univ., The Cornell CTU
  • Washington
    • Seattle, Washington, United States, 90033-1079
      • University of Washington AIDS CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Neurologic AIDS Research Consortium (NARC)
• Investigators: Study Chair: Victor Valcour, M.D., University of Hawaii; Study Chair: Russell Bartt, M.D., Cook County Hospital and Rush-Presbyterian St. Luke's Medical Center

Publications and helpful links

General Publications

• Wulff EA, Wang AK, Simpson DM. HIV-associated peripheral neuropathy: epidemiology, pathophysiology and treatment. Drugs. 2000 Jun;59(6):1251-60. doi: 10.2165/00003495-200059060-00005.
• Simpson DM, Katzenstein D, Haidich B, Millington D, Yiannoutsos C, Schifitto G, McArthur J; AIDS Clinical Trials Group Protocol 291/860 Study Team. Plasma carnitine in HIV-associated neuropathy. AIDS. 2001 Nov 9;15(16):2207-8. doi: 10.1097/00002030-200111090-00025. No abstract available.
• Polydefkis M, Yiannoutsos CT, Cohen BA, Hollander H, Schifitto G, Clifford DB, Simpson DM, Katzenstein D, Shriver S, Hauer P, Brown A, Haidich AB, Moo L, McArthur JC. Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology. 2002 Jan 8;58(1):115-9. doi: 10.1212/wnl.58.1.115.
• Scarpini E, Sacilotto G, Baron P, Cusini M, Scarlato G. Effect of acetyl-L-carnitine in the treatment of painful peripheral neuropathies in HIV+ patients. J Peripher Nerv Syst. 1997;2(3):250-2.

Study record dates

Study Major Dates

• Study Start: December 6, 2022
• Primary Completion: December 6, 2022
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: December 3, 2002
• First Submitted That Met QC Criteria: December 3, 2002
• First Posted (Estimate): December 4, 2002

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Acetylcarnitine; Dideoxynucleosides; Epidermis; Biopsy; Immunohistochemistry; Nerve Fibers; Treatment Experienced
• Additional Relevant MeSH Terms: Neuromuscular Diseases; Peripheral Nervous System Diseases; Nervous System Diseases; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Nootropic Agents; Acetylcarnitine
• Other Study ID Numbers: A5157; 10004 (DAIDS ES); ACTG A5157

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No