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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
This study has been completed.
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000702
  Purpose

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.


Condition Intervention Phase
AIDS Dementia Complex
HIV Infections
Drug: Zidovudine
Phase III

MedlinePlus related topics: AIDS Dementia
Drug Information available for: Zidovudine
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Double-Blind
Official Title: 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

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 315
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000702

Locations
United States, California
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
UCLA CARE Ctr
Los Angeles, California, United States, 90095
Stanford Univ School of Medicine
Stanford, California, United States, 94305
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Louisiana
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, United States, 70112
Louisiana State Univ Med Ctr / Tulane Med School
New Orleans, Louisiana, United States, 70112
Tulane Univ School of Medicine
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Harvard (Massachusetts Gen Hosp)
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
United States, New York
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Mount Sinai Med Ctr
New York, New York, United States, 10029
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, United States, 10003
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
United States, Washington
Univ of Washington
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Investigators
Study Chair: R Price
  More Information

Click here for more information about Zidovudine  This link exits the ClinicalTrials.gov site

Publications:
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.
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)

Study ID Numbers: ACTG 005
Study First Received: November 2, 1999
Last Updated: July 11, 2008
ClinicalTrials.gov Identifier: NCT00000702  
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
AIDS Dementia Complex
Zidovudine

Study placed in the following topic categories:
Sexually Transmitted Diseases, Viral
AIDS Dementia Complex
Acquired Immunodeficiency Syndrome
Zidovudine
Central Nervous System Diseases
Brain Diseases
Immunologic Deficiency Syndromes
Cognition Disorders
Virus Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
HIV Infections
Sexually Transmitted Diseases
Dementia
Retroviridae Infections
Delirium

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Communicable Diseases
RNA Virus Infections
Anti-HIV Agents
Slow Virus Diseases
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Nervous System Diseases
Enzyme Inhibitors
Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009