A Multicenter Placebo-Controlled Double-Blind Trial to Evaluate Azidothymidine (AZT) Treatment of the AIDS Dementia Complex and Central Nervous System (CNS) Human Immunodeficiency Virus (HIV) Infection

NCT ID: NCT00000702

Last Updated: 2021-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

315 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1990-08-31

Brief Summary

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To test whether zidovudine (AZT) is useful as a treatment for the neurologic syndrome called AIDS dementia complex. To determine how long AZT takes to reach cerebral spinal fluid (CSF), how long, and at what concentration it is found there.

HIV infection can result in impairment in the function of the brain and spinal cord, leading to disturbances in the ability to think clearly and in strength and coordination. This disorder, which has been called the AIDS dementia complex, may be due to a direct effect of HIV on the nervous system. It is known that AZT does get into the brain to some extent, where it may reduce growth of HIV. It is hoped that AZT will stabilize or improve the symptoms of the AIDS dementia complex.

Detailed Description

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HIV infection can result in impairment in the function of the brain and spinal cord, leading to disturbances in the ability to think clearly and in strength and coordination. This disorder, which has been called the AIDS dementia complex, may be due to a direct effect of HIV on the nervous system. It is known that AZT does get into the brain to some extent, where it may reduce growth of HIV. It is hoped that AZT will stabilize or improve the symptoms of the AIDS dementia complex.

The study is done in 2 stages. In Stage 1, patients are randomized to receive placebo or 1 of 2 doses of AZT. Stage 1 lasts for 4 months. In Stage 2, patients who were initially treated with placebo are randomized again and all patients receive AZT. Stage 2 lasts an additional 12 months, during which time there are periodic medical and neurologic evaluations. Before beginning treatment, all patients have a lumbar puncture and a computerized tomographic (CT) scan of the brain. The lumbar puncture is repeated twice during and once at the end of Stage 1; the CT scan is also repeated at the end of Stage 1. Patients receiving AZT in either stage 1 or Stage 2 are seen by their physicians every week for the first 4 weeks and every other week thereafter for the first 4 months of receiving the drug. After 4 months, patients are seen by their physicians at 4 to 12 week intervals.

Conditions

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AIDS Dementia Complex HIV Infections

Keywords

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AIDS Dementia Complex Zidovudine

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Zidovudine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Concurrent Medication:

Allowed:

* Aspirin, in modest doses.
* Ibuprofen, in modest doses.
* Maintenance antibiotic therapy posttherapy for an AIDS-defining opportunistic infection.

Concurrent Treatment:

Allowed:

* Blood transfusion if cardiovascular status is compromised.

Exclusion Criteria

* Active substance abuse.

Co-existing Condition:

Patients with the following conditions will be excluded:

* Concurrent or previous central nervous system infections or neoplasms.
* Active AIDS-defining opportunistic infection.
* Severe premorbid psychiatric illness.
* Confounding neurological disease.
* Concurrent neoplasms.

Concurrent Medication:

Excluded:

* Maintenance methadone or naltrexone.
* Acetaminophen.
* Mood- or central nervous system-altering drugs.
* Zidovudine for Pneumocystis carinii pneumonia (PCP).
* Acyclovir.
* Rifampin or derivatives.
* Drugs with antiretroviral activity.
* Experimental agents.

The following patients will be excluded from the study:

* Patients requiring ongoing therapy for an AIDS-defining opportunistic infection.
* Patients with a history of Mycobacterium avium intracellulare infection.
* Patients with a history of Pneumocystis carinii pneumonia infection.
* Patients with a daily temperature of 38 degrees C or more for 1 month.

Prior Medication:

Excluded:

* Zidovudine (AZT).
* Excluded within 14 days of study entry:
* Systemic anti-infectives.
* Excluded within 30 days of study entry:
* Immunomodulators and biologic response modifiers.
* Any investigational agent.
* Cytotoxic chemotherapy for Kaposi's sarcoma.

Prior Treatment:

Excluded:

* Radiation therapy.

Patients must demonstrate the following clinical and laboratory findings:

* No currently active AIDS-defining opportunistic infections.
* One negative blood culture for Mycobacterium avium intracellulare within 4-6 weeks prior to study entry.
* Constitutionally well without persistent fever.
* Less than 25 Kaposi's sarcoma lesions and less than 10 new lesions during the 30 days prior to study entry. Patients may have stable or indolently progressive mucocutaneous Kaposi's sarcoma.
* Characteristic clinical symptoms and signs of AIDS dementia complex.
* Abnormalities on 2 or more of 7 neuropsychological motor tests in the Neurological Screening Battery.
* Estimated premorbid IQ equal to or greater than 70 (+ or - 5), which is consistent with completion of sixth grade.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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R Price

Role: STUDY_CHAIR

Locations

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UCLA CARE Ctr

Los Angeles, California, United States

Site Status

Univ of California / San Diego Treatment Ctr

San Diego, California, United States

Site Status

Stanford Univ School of Medicine

Stanford, California, United States

Site Status

Univ of Miami School of Medicine

Miami, Florida, United States

Site Status

Charity Hosp / Tulane Univ Med School

New Orleans, Louisiana, United States

Site Status

Louisiana State Univ Med Ctr / Tulane Med School

New Orleans, Louisiana, United States

Site Status

Tulane Univ School of Medicine

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Hosp

Baltimore, Maryland, United States

Site Status

Harvard (Massachusetts Gen Hosp)

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med Ctr

Boston, Massachusetts, United States

Site Status

SUNY / Erie County Med Ctr at Buffalo

Buffalo, New York, United States

Site Status

City Hosp Ctr at Elmhurst / Mount Sinai Hosp

Elmhurst, New York, United States

Site Status

Beth Israel Med Ctr / Peter Krueger Clinic

New York, New York, United States

Site Status

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Site Status

Mem Sloan - Kettering Cancer Ctr

New York, New York, United States

Site Status

Mount Sinai Med Ctr

New York, New York, United States

Site Status

Univ of Rochester Medical Center

Rochester, New York, United States

Site Status

Bronx Municipal Hosp Ctr/Jacobi Med Ctr

The Bronx, New York, United States

Site Status

Jack Weiler Hosp / Bronx Municipal Hosp

The Bronx, New York, United States

Site Status

Julio Arroyo

West Columbia, South Carolina, United States

Site Status

Univ of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Sidtis JJ, Gatsonis C, Price RW, Singer EJ, Collier AC, Richman DD, Hirsch MS, Schaerf FW, Fischl MA, Kieburtz K, et al. Zidovudine treatment of the AIDS dementia complex: results of a placebo-controlled trial. AIDS Clinical Trials Group. Ann Neurol. 1993 Apr;33(4):343-9. doi: 10.1002/ana.410330403.

Reference Type BACKGROUND
PMID: 8489204 (View on PubMed)

Price RW, Koch MA, Sidtis JJ, Feinberg J, Collier A, Kennedy C, Singer E, Price S. Zidovudine (AZT) treatment of the AIDS dementia complex (ADC): results of a placebo-controlled, multicentered therapeutic trial. Int Conf AIDS. 1989 Jun 4-9;5:407 (abstract no WBP331)

Reference Type BACKGROUND

Other Identifiers

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10981

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 005

Identifier Type: -

Identifier Source: org_study_id