Nerve Damage in Patients With HIV Infection Who Have Been Treated With Anti-HIV Drugs

NCT ID: NCT00017771

Last Updated: 2013-07-29

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 100 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2001-06-30
• Study Completion Date: 2004-07-31

Brief Summary

The purpose of this study is to find out what might increase nerve damage in people with HIV who have taken drugs for treatment of HIV disease. Another purpose is to see if nerve exams are done correctly before clinical research sites enroll HIV-infected patients.

Nerve damage is common in patients with HIV infection and can cause serious problems. The factors that place patients at risk are not well understood. This study will examine these factors in patients with advanced HIV infection and who have been taking anti-HIV drugs.

Detailed Description

Neurological complications in HIV infection are common and are significant sources of mortality and morbidity. The associated risk factors have not been clearly defined. Several studies have patients who are suited for analysis of peripheral neuropathy and can address the important clinical question of when a subject with asymptomatic neuropathy is most at risk for progressing to painful neuropathy. Some patients in this population with advanced HIV disease will likely have asymptomatic peripheral neuropathy at baseline, and will present an excellent opportunity for prospective study. Detailed quantitative assessments will be carried out to determine the incidence and course of peripheral neuropathy in this population. Risk factors for the development of new peripheral neuropathy, worsening of existing neuropathy, and progression to symptomatic peripheral neuropathy, such as CD4+ cell counts, HIV-1 viral load, and prior nucleoside analogue use, will be evaluated. The potential additive neurotoxic effects of hydroxyurea exposure in this population can also be analyzed.

HIV-infected patients are characterized for the presence or absence of neuropathy at [AS PER AMENDMENT 03/05/02: screening], baseline, Week 24, and Week 48. Entry variables are analyzed to determine predictors of progression from asymptomatic to symptomatic neuropathy or for worsening of symptomatic neuropathy. HIV-uninfected control volunteers have 1 visit [AS PER AMENDMENT 03/05/02: or 2 visits] for nerve conduction and Quantitative Sensory Testing (QST) evaluations to demonstrate proficiency with the testing methods prior to the enrollment of HIV-infected patients. HIV-infected patients are evaluated with the components of the Total Neuropathy Score (TNS) which includes signs (motor function, sensory function, and reflexes), symptoms (motor symptoms and sensory symptoms), QST (CASE IV - vibratory, cooling, and heat pain thresholds), and nerve conduction studies (sural nerve and peroneal nerve). Other evaluations include the Gracely Pain Scale and Visual Analog Scale pain diaries, paired skin biopsies from the right thigh and distal leg (total of 2), and peripheral blood lymphocyte analysis for quantitation of mitochondrial DNA content at entry and final study visit.

Conditions

HIV Infections; Peripheral Nervous System Disease

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

Control volunteers will be eligible for this study if they:

• Are HIV negative.
• Are at least 18 years old.

Patients will be eligible for this study if they:

• Are HIV positive.
• Are at least 13 years old and can provide written consent from parent or guardian if under 18 years of age.
• Have taken anti-HIV drugs for at least 15 straight weeks any time in the past.
• Have a CD4 count of less than 300 cells/mm3.

Exclusion Criteria

Control volunteers will not be eligible for this study if they:

• Have any nerve-related problems.
• Have diabetes and nerve damage related to diabetes.
• Have long-term illness the doctor feels would interfere with the study.

Patients will not be eligible for this study if they:

• Have had spinal surgery.
• Have taken insulin or oral hypoglycemic products for diabetes mellitus within 30 days prior to study entry. Dietary control for diabetes is allowed.
• Have nerve damage related to diabetes.
• Have a nerve condition unrelated to HIV infection or antiretroviral therapy.
• Have alcohol-related medical complications within 6 months of study entry.
• Have vitamin B12 levels of less than 200 pg/ml or a history of vitamin B12 deficiency.

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Simpson

Role: STUDY_CHAIR

Locations

Univ of Alabama at Birmingham

Birmingham, Alabama, United States

UCLA CARE Ctr

Los Angeles, California, United States

Univ of Colorado Health Sciences Ctr

Denver, Colorado, United States

Univ of Hawaii

Honolulu, Hawaii, United States

The CORE Ctr

Chicago, Illinois, United States

Indiana Univ Hosp

Indianapolis, Indiana, United States

Methodist Hosp of Indiana / Life Care Clinic

Indianapolis, Indiana, United States

Wishard Hosp

Indianapolis, Indiana, United States

Johns Hopkins Hosp

Baltimore, Maryland, United States

Washington Univ / St Louis Connect Care

St Louis, Missouri, United States

Washington Univ School of Medicine

St Louis, Missouri, United States

Beth Israel Med Ctr

New York, New York, United States

Cornell Univ Med Ctr

New York, New York, United States

Univ of Rochester Medical Center

Rochester, New York, United States

Univ of Pennsylvania

Philadelphia, Pennsylvania, United States

Mount Sinai Med Ctr

Pittsburgh, Pennsylvania, United States

Univ of Texas, Southwestern Med Ctr of Dallas

Dallas, Texas, United States

Univ of Washington

Seattle, Washington, United States

Countries

United States

References

Simpson DM, Kitch D, Evans SR, McArthur JC, Asmuth DM, Cohen B, Goodkin K, Gerschenson M, So Y, Marra CM, Diaz-Arrastia R, Shriver S, Millar L, Clifford DB; ACTG A5117 Study Group. HIV neuropathy natural history cohort study: assessment measures and risk factors. Neurology. 2006 Jun 13;66(11):1679-87. doi: 10.1212/01.wnl.0000218303.48113.5d.

Reference Type: RESULT

PMID: 16769940 (View on PubMed)

Roda RH, Bargiela D, Chen W, Perry K, Ellis RJ, Clifford DB, Bharti A, Kallianpur AR, Oliveira MF, Diaz MM, Rubin LH, Gavegnano C, McArthur JC, Hoke A, Polydefkis M. Large Mitochondrial DNA Deletions in HIV Sensory Neuropathy. Neurology. 2021 Jul 13;97(2):e156-e165. doi: 10.1212/WNL.0000000000012142. Epub 2021 May 4.

Reference Type: DERIVED

PMID: 33947785 (View on PubMed)

Other Identifiers

AACTG A5117

Identifier Type: -

Identifier Source: secondary_id

ACTG A5117

Identifier Type: -

Identifier Source: secondary_id

10935

Identifier Type: REGISTRY

Identifier Source: secondary_id

A5117

Identifier Type: -

Identifier Source: org_study_id