Clinical trial NCT00000702: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: AIDS Dementia Complex
HIV Infections
Keywords: AIDS Dementia Complex
Zidovudine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 315
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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: 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 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Ctr
state: California
city: San Diego
country: United States
facility: Univ of California / San Diego Treatment Ctr
state: California
city: Stanford
country: United States
facility: Stanford Univ School of Medicine
state: California
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
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: Boston
country: United States
facility: Harvard (Massachusetts Gen Hosp)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med Ctr
state: Massachusetts
city: Bronx
country: United States
facility: Bronx Municipal Hosp Ctr/Jacobi Med Ctr
state: New York
city: Bronx
country: United States
facility: Jack Weiler Hosp / Bronx Municipal Hosp
state: New York
city: Buffalo
country: United States
facility: SUNY / Erie County Med Ctr at Buffalo
state: New York
city: Elmhurst
country: United States
facility: City Hosp Ctr at Elmhurst / Mount Sinai Hosp
state: New York
city: New York
country: United States
facility: Beth Israel Med Ctr / Peter Krueger Clinic
state: New York
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: New York
country: United States
facility: Mount Sinai Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
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: R Price
role: STUDY_CHAIR
References:
citation: 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.
citation: 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)