Clinical trial NCT00000709: An Open Trial of Zidovudine (AZT) Treatment of the AIDS Dementia Complex in Patients With AIDS or Low CD4+ Lymphocyte Counts
Official title: An Open Trial of Zidovudine (AZT) Treatment of the AIDS Dementia Complex in Patients With AIDS or Low CD4+ Lymphocyte Counts
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: AIDS Dementia Complex
HIV Infections
Keywords: Neuropsychological Tests
AIDS Dementia Complex
Zidovudine
CD4-Positive T-Lymphocytes
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 50
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: New Orleans
country: United States
facility: Charity Hosp / Tulane Univ Med School
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana State Univ Med Ctr / Tulane Med School
state: Louisiana
city: New Orleans
country: United States
facility: Tulane Univ School of Medicine
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hosp
state: Maryland
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mem Sloan - Kettering Cancer Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: Univ Hosp of Cleveland / Case Western Reserve Univ
state: Ohio
city: West Columbia
country: United States
facility: Julio Arroyo
state: South Carolina
city: Seattle
country: United States
facility: Univ of Washington
state: Washington
Study officials:
name: RW Price
role: STUDY_CHAIR
References: