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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00050271

Collaborator

Neurologic AIDS Research Consortium (NARC) (Other)

Enrollment

Locations

2.5

Patients Per Site

Study Details

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	N/A

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

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 :

Jan 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford CRS	Palo Alto	California	United States	94305
2	The Ponce de Leon Ctr. CRS	Atlanta	Georgia	United States	30308
3	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States
4	Northwestern University CRS	Chicago	Illinois	United States	60611-3015
5	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
6	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287-8106
7	Washington U CRS	Saint Louis	Missouri	United States	63108-2138
8	Beth Israel Med. Ctr., ACTU	New York	New York	United States	10003
9	Weill Med. College of Cornell Univ., The Cornell CTU	New York	New York	United States
10	University of Washington AIDS CRS	Seattle	Washington	United States	90033-1079
11	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