Clinical Trial: 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.

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)

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 Treatment or Intervention Phase
AIDS Dementia Complex
HIV Infections
 Drug: Zidovudine
Phase III

MedlinePlus related topics:  AIDS;   Dementia

Study Type: Interventional
Study Design: Treatment, Open Label

Further Study Details: 

Expected Total Enrollment:  50

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 above,  Genders Eligible for Study:  Both

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.

Location Information


California
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States

Louisiana
      Charity Hosp / Tulane Univ Med School, New Orleans,  Louisiana,  70112,  United States

      Louisiana State Univ Med Ctr / Tulane Med School, New Orleans,  Louisiana,  70112,  United States

      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States

Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States

New York
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States

      Mem Sloan - Kettering Cancer Ctr, New York,  New York,  10021,  United States

      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States

North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States

Ohio
      Univ Hosp of Cleveland / Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States

South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States

Washington
      Univ of Washington, Seattle,  Washington,  98105,  United States

Study chairs or principal investigators

RW Price,  Study Chair

More Information

Click here for more information about Zidovudine

Study ID Numbers:  ACTG 061
Record last reviewed:  May 1999
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000709
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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