An Open Trial of Zidovudine (AZT) Treatment of the AIDS Dementia Complex in Patients With AIDS or Low CD4+ Lymphocyte Counts

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000709
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

To provide accurate and complete neurologic assessment of the course of the AIDS dementia complex in patients treated with zidovudine (AZT). The study will determine how frequently patients improve, how long improvement is sustained, and the magnitude and functional significance of improvement.

Individuals with AIDS frequently suffer central nervous system (CNS) problems that are characterized by cognitive, motor, and behavioral deficits, in a disorder known as AIDS dementia complex. Clinical experience suggests that its course is often progressive, going from initial symptoms to moderate or severe dementia within several months. Accumulating evidence now suggests that direct brain infection by the HIV virus is the likely cause of the AIDS dementia complex. Case reports suggest that therapy with AZT, which has been shown to be a strong inhibitor of HIV replication in vitro, may alleviate the AIDS dementia complex. This study will help define the natural history of the AIDS dementia complex in treated patients.


Condition Intervention Phase
AIDS Dementia Complex
HIV Infections
Drug: Zidovudine
Phase 3

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Trial of Zidovudine (AZT) Treatment of the AIDS Dementia Complex in Patients With AIDS or Low CD4+ Lymphocyte Counts

Resource links provided by NLM:


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

Estimated Enrollment: 50
Study Completion Date: February 1990
Detailed Description:

Individuals with AIDS frequently suffer central nervous system (CNS) problems that are characterized by cognitive, motor, and behavioral deficits, in a disorder known as AIDS dementia complex. Clinical experience suggests that its course is often progressive, going from initial symptoms to moderate or severe dementia within several months. Accumulating evidence now suggests that direct brain infection by the HIV virus is the likely cause of the AIDS dementia complex. Case reports suggest that therapy with AZT, which has been shown to be a strong inhibitor of HIV replication in vitro, may alleviate the AIDS dementia complex. This study will help define the natural history of the AIDS dementia complex in treated patients.

All patients receive AZT for 24 weeks. Patients are seen weekly for the first 4 weeks, every other week for the next 8 weeks, and then every 4 weeks until the completion of the study for neuropsychological evaluation. This evaluation includes lumbar puncture, and either computerized tomography or magnetic resonance imaging.

  Eligibility

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

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Prophylactic therapy for Pneumocystis carinii pneumonia (PCP); aerosol pentamidine is the preferred method.
  • Maintenance anticonvulsant therapy following a seizure in the context of the AIDS dementia complex.
  • Patients taking anticonvulsants should have their anticonvulsant blood levels measured prior to starting zidovudine (AZT) or with changes in AZT dosage.
  • Phenytoin, carbamazepine, and valproic acid.
  • Judicious use of benzodiazepams.
  • For analgesia or fever, modest doses of aspirin, Tylenol, or ibuprofen.
  • Use of major mood or central nervous system altering drugs is discouraged and should be documented.

Patients with the following are included:

  • An estimated pre-illness IQ = or > 70.
  • A general neurodiagnostic evaluation before entry which will include a computerized tomographic (CT) scan or magnetic resonance imaging (MRI) scan and a lumbar puncture.
  • Stable or indolently progressive mucocutaneous Kaposi's sarcoma with < 25 lesions and onset of < 10 new lesions during the 30-day period prior to study entry.
  • Chronic seizure disorders requiring anticonvulsant therapy as long as the seizures are not associated with a fixed neurologic deficit.
  • A blood HIV culture and p24 antigen capture assay at the time of the lumbar puncture. A second p24 antigen assay on study entry. Informed consent form must be signed by the patient, legal guardian, or parent.

Active substance abuse that would limit a patient's cooperation or evaluation.

Exclusion Criteria

Co-existing Condition:

Patients with the following will be excluded from the study:

  • Active, symptomatic AIDS-associated opportunistic infections requiring ongoing maintenance therapy.
  • Persistent fever, active persistent diarrhea, or continued severe weight loss.
  • Severe premorbid psychiatric illness.
  • Confounding neurologic disease or deficit.
  • Concurrent or previous central nervous system infections or neoplasms.
  • Concurrent active neoplasms other than basal cell carcinoma of the skin and mucocutaneous Kaposi's sarcoma.

Concurrent Medication:

Excluded:

  • Major psychotropic medication including tricyclic antidepressants, MAO inhibitors, phenothiazines, butyrophenones, barbiturates, or amphetamines.
  • Cimetidine.
  • Ranitidine.
  • Probenecid.
  • Indomethacin.
  • Acyclovir (ACV) prophylaxis for recurrent Herpes simplex.

Patients with the following will be excluded from the study:

  • Active, symptomatic AIDS-associated opportunistic infections requiring ongoing maintenance therapy.
  • Persistent fever, active persistent diarrhea, or continued severe weight loss.
  • Severe premorbid psychiatric illness.
  • Confounding neurologic disease or deficit.
  • Concurrent or previous central nervous system infections or neoplasms.
  • Concurrent active neoplasms other than basal cell carcinoma of the skin and mucocutaneous Kaposi's sarcoma.

Prior Medication:

Excluded within 2 weeks of study entry or for greater than 2 weeks of therapy:

  • Zidovudine (AZT).
  • Patients must not have previously exhibited toxic reaction to AZT.
  • Excluded within 30 days of study entry:
  • Immunomodulators and biologic response modifiers, including systemic steroids.
  • Any investigational agent.
  • Cytotoxic chemotherapy for Kaposi's sarcoma.

Prior Treatment:

Excluded within 30 days of study entry:

  • Radiation therapy.
  • Excluded within 2 weeks of study entry:
  • Blood transfusion.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000709

Locations
United States, California
UCLA CARE Ctr
Los Angeles, California, United States, 90095
United States, Louisiana
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
Charity Hosp / Tulane Univ Med School
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, New York
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
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, Ohio
Univ Hosp of Cleveland / Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
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: RW Price
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000709     History of Changes
Other Study ID Numbers: ACTG 061, 11035
Study First Received: November 2, 1999
Last Updated: March 15, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Neuropsychological Tests
AIDS Dementia Complex
Zidovudine
CD4-Positive T-Lymphocytes

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
AIDS Dementia Complex
Dementia
HIV Infections
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Mental Disorders
Nervous System Diseases
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014