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

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00017771

Collaborator

(none)

100

Enrollment

Locations

Duration (Months)

5.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections Peripheral Nervous System Disease

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.

Study Design

Study Type:

Observational

Actual Enrollment :

100 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

A Pathophysiologic Study of Development of Distal Symmetrical Polyneuropathy in Individuals With Advanced HIV-1 Infection and Prior Antiretroviral Exposure

Study Start Date :

Jun 1, 2001

Actual Study Completion Date :

Jul 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

This study has been changed to modify the exclusion criteria. Earlier versions did not include some of these exclusion criteria.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Univ of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	UCLA CARE Ctr	Los Angeles	California	United States	90095
3	Univ of Colorado Health Sciences Ctr	Denver	Colorado	United States	80262
4	Univ of Hawaii	Honolulu	Hawaii	United States	96816
5	The CORE Ctr	Chicago	Illinois	United States	60612
6	Indiana Univ Hosp	Indianapolis	Indiana	United States	462025250
7	Methodist Hosp of Indiana / Life Care Clinic	Indianapolis	Indiana	United States	46202
8	Wishard Hosp	Indianapolis	Indiana	United States	46202
9	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
10	Washington Univ / St Louis Connect Care	Saint Louis	Missouri	United States	63108
11	Washington Univ School of Medicine	St Louis	Missouri	United States	63108
12	Beth Israel Med Ctr	New York	New York	United States	10003
13	Cornell Univ Med Ctr	New York	New York	United States	10021
14	Univ of Rochester Medical Center	Rochester	New York	United States	14642
15	Univ of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
16	Mount Sinai Med Ctr	Pittsburgh	Pennsylvania	United States	15213
17	Univ of Texas, Southwestern Med Ctr of Dallas	Dallas	Texas	United States	75390
18	Univ of Washington	Seattle	Washington	United States	98104