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

• ClinicalTrials.gov Identifier: NCT00050271
• Recruitment Status: Completed
• First Posted: December 4, 2002
• Last Update Posted: May 21, 2012
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: Neurologic AIDS Research Consortium (NARC)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
HIV Infections; Peripheral Nervous System Diseases	Drug: Acetyl-L-carnitine	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Dose-Escalation Pilot Study of Acetyl-L-Carnitine for the Treatment of Dideoxynucleoside-Associated Distal Symmetric Peripheral Neuropathy
• Actual Study Completion Date: January 2007

Arms and Interventions

Outcome Measures

Eligibility Criteria

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

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
• 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.

Contacts and Locations

Locations

United States, California

Stanford CRS

Palo Alto, California, United States, 94305

United States, Georgia

The Ponce de Leon Ctr. CRS

Atlanta, Georgia, United States, 30308

United States, Hawaii

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, United States

United States, Illinois

Northwestern University CRS

Chicago, Illinois, United States, 60611-3015

Cook County Hosp. CORE Ctr.

Chicago, Illinois, United States, 60612

United States, Maryland

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States, 21287-8106

United States, Missouri

Washington U CRS

St. Louis, Missouri, United States, 63108-2138

United States, New York

Beth Israel Med. Ctr., ACTU

New York, New York, United States, 10003

Weill Med. College of Cornell Univ., The Cornell CTU

New York, New York, United States

United States, Washington

University of Washington AIDS CRS

Seattle, Washington, United States, 90033-1079

Puerto Rico

Puerto Rico-AIDS CRS

San Juan, Puerto Rico, 00936-5067

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

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

More Information

Additional Information:

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Publications:

Wulff EA, Wang AK, Simpson DM. HIV-associated peripheral neuropathy: epidemiology, pathophysiology and treatment. Drugs. 2000 Jun;59(6):1251-60. Review.

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.

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.

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00050271
• Other Study ID Numbers: A5157; 10004 ( Registry Identifier: DAIDS ES ); ACTG A5157
• First Posted: December 4, 2002
• Last Update Posted: May 21, 2012
• Last Verified: May 2012

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Acetylcarnitine; Dideoxynucleosides; Epidermis; Biopsy; Immunohistochemistry; Nerve Fibers; Treatment Experienced

Additional relevant MeSH terms:

Peripheral Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Acetylcarnitine; Vitamin B Complex; Vitamins; Micronutrients; Nutrients; Growth Substances; Physiological Effects of Drugs; Nootropic Agents