Clinical trial NCT00000867: A Study to Evaluate the Use of Memantine In Combination With Anti-HIV Drugs to Treat AIDS Dementia Complex (ADC)
Official title: A Phase II, Randomized, Double Blind, Placebo-Controlled Trial of Memantine for AIDS Dementia Complex (ADC) as Concurrent Treatment With Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: AIDS Dementia Complex
HIV Infections
Keywords: Drug Therapy, Combination
Administration, Oral
AIDS Dementia Complex
Zidovudine
Anti-HIV Agents
Memantine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the safety and effectiveness of memantine, an experimental drug, in improving AIDS dementia complex (ADC).

The symptoms of ADC can be improved with zidovudine (ZDV). However, ZDV therapy has been associated with significant toxicities, and the effectiveness of ZDV seems to decrease during the second and third years of therapy. The effectiveness of other antiretroviral drugs as treatment for ADC is not known, so it is important to explore alternative therapies.

Detailed description: The signs and symptoms of the AIDS Dementia Complex can be alleviated by zidovudine (ZDV). However, ZDV therapy has been associated with significant toxicities, particularly bone marrow suppression. The efficacy of ZDV appears to decrease during the second and third years of therapy. It is not known whether this reflects cumulative toxicity. In addition, the efficacy of other antiretroviral agents remains uncertain. Hence, adjunctive therapy for cognitive and motor symptoms of AIDS is important.

Patients will be randomized to one of the following 2 arms:

Arm 1 receives memantine plus concurrent antiretroviral therapy; Arm 2 receives placebo plus concurrent antiretroviral therapy. The initial dose of memantine is increased each week for the next 3 weeks, unless a maximum tolerated dose is reached. Following a 16-week evaluation period there is a 4-week washout prior to re-assessment. After the washout period, all patients, including those formerly randomized to the placebo arm, are given the opportunity to receive an open-label, 12-week administration of memantine. \[AS PER AMENDMENT 4/6/99: The open-label phase is extended by 48 weeks to a total of 60 weeks of therapy. Patients who did not receive the initial 12 weeks of open-label treatment are eligible still for the 48-week open-label treatment phase.\]

Eligibility criteria: Inclusion Criteria

You may be eligible for this study if you:

* Are HIV positive.
* Have been diagnosed with AIDS dementia complex (ADC).
* Have an estimated IQ of at least 70 (before the onset of ADC) or the ability to read at a 6th grade level.
* Have impaired mental skills.
* Are age18 or older.

Exclusion Criteria

You will not be eligible for this study if you:

* Have a history of a neurologic disease unrelated to HIV infection.
* Have a history of chronic seizures or head injuries.
* Have a history of central nervous system infections.
* Have certain cancers.
* Have any psychiatric illness.
* Have an active AIDS-defining opportunistic infection.
* Are pregnant or breast-feeding.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Honolulu
country: United States
facility: Queens Med. Ctr.
state: Hawaii
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp. CORE Ctr.
state: Illinois
city: Lexington
country: United States
facility: The Univ. of Kentucky, Lexington A2405 CRS
state: Kentucky
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - East Campus A0102 CRS
state: Massachusetts
city: St. Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Omaha
country: United States
facility: Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
state: Nebraska
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: Beth Israel Med. Ctr. (Mt. Sinai)
state: New York
city: New York
country: United States
facility: Mt. Sinai Med. Ctr. (N.Y.) A1801 CRS
state: New York
city: New York
country: United States
facility: Mt. Sinai Med. Ctr. A0404 CRS
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
name: Bradford Navia
role: STUDY_CHAIR
name: Richard Price
role: STUDY_CHAIR
References:
citation: Letendre S, Zheng J, Yiannoutsos C, Lopez A, Ellis R, Marquie-Beck J, Zimmerman J, Gendelman H, Navia B, and The ACTG 301 and 700 Study Teams. Chemokines Correlate with Cerebral Metabolites on Magnetic Resonance Spectroscopy: A Substudy of ACTG 301 and 700. CROI 2004. Abstract 29.
citation: Schifitto G, Navia BA, Yiannoutsos CT, Marra CM, Chang L, Ernst T, Jarvik JG, Miller EN, Singer EJ, Ellis RJ, Kolson DL, Simpson D, Nath A, Berger J, Shriver SL, Millar LL, Colquhoun D, Lenkinski R, Gonzalez RG, Lipton SA; Adult AIDS Clinical Trial Group (ACTG) 301; 700 Teams; HIV MRS Consortium. Memantine and HIV-associated cognitive impairment: a neuropsychological and proton magnetic resonance spectroscopy study. AIDS. 2007 Sep 12;21(14):1877-86. doi: 10.1097/QAD.0b013e32813384e8.
citation: Zhao Y, Navia BA, Marra CM, Singer EJ, Chang L, Berger J, Ellis RJ, Kolson DL, Simpson D, Miller EN, Lipton SA, Evans SR, Schifitto G; Adult Aids Clinical Trial Group (ACTG) 301 Team. Memantine for AIDS dementia complex: open-label report of ACTG 301. HIV Clin Trials. 2010 Jan-Feb;11(1):59-67. doi: 10.1310/hct1101-59.