The purpose of this study is to evaluate the use of selegiline transdermal system (STS) in the treatment of decreased mental function in patients with HIV. A decrease in mental function often occurs in patients with HIV. Antiretroviral drugs are used to treat this but are not entirely effective. Some other therapy could play a role. The drug selegiline, in a pill form, is used to treat Parkinson's disease, a serious brain disorder. It is believed this drug might protect the brain and repair some damage. This study will use this drug in a "patch" form, which has not been approved by FDA, to see if it helps with decreased mental function in patients with HIV.

Condition	Treatment or Intervention	Phase
Cognition Disorders HIV Infections	Drug: Selegiline hydrochloride	Phase II

Further Study Details: 

Expected Total Enrollment:  120

Cognitive impairment is a common sequela of HIV infection that can progress to dementia. Antiretroviral agents are the only current therapy, but treatment response is frequently unsatisfactory, short lived, or the agents are poorly tolerated in doses adequate for central nervous system penetration. An adjunctive therapy that interferes with the cascade of events triggered by the virus is likely to play an important role. Oral selegiline is an approved and marketed drug for the symptomatic treatment of Parkinson's disease. Studies suggest that selegiline has a neuroprotective effect and that it may exert a "rescue effect" on dying and injured neurons. This study proposes to use transdermal selegiline, which may deliver a greater dose level than oral administration, in the treatment of HIV-associated cognitive impairment.

This is a two step study, with each step lasting 24 weeks. Step 1 is double-blind and Step 2 is open label. At entry, patients are randomized to one of three arms. Arm 1 receives a lower-dose STS, Arm 2 receives a higher-dose STS, and Arm 3 receives a placebo. One STS patch will be applied daily at the same time for 24 weeks. Patients are evaluated at the clinic at entry and at Weeks 2, 4, 8, 12, 16, and 24. Cognitive status will be evaluated by performance on a series of neuropsychological assessments. Patients who complete Step 1 may participate in Step 2 and receive the same or a safer or more effective dose as determined in Step 1. Patients on placebo in Step 1 receive active STS treatment. The STS patch is applied once daily for an additional 24 weeks and patients are evaluated at the clinic at Weeks 28, 36, and 48.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• HIV positive
• Stable anti-HIV therapy or no anti-HIV therapy for at least 8 weeks prior to study screening
• AIDS Dementia Complex Stage > 0
• Decreased mental function as shown by tests during screening
• IQ >= 70
• Acceptable methods of contraception during study and for 3 months following study

Exclusion Criteria

• Tumor other than basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma, that does not involve a large organ or which does not require chemotherapy
• Serious mental illness that, in the opinion of the doctor, might interfere with the study
• Reserpine or meperidine use within 7 days prior to study entry
• Nefazodone within 14 days prior to study entry
• Monoamine oxidase inhibitor, including selegiline, within 30 days prior to study entry
• Sympathomimetic medications, including over the counter diet and cold (oral or nasal) remedies, within 14 days of study entry
• Decreased blood pressure when standing up
• Uncontrolled high blood pressure
• AIDS-related infection within 30 days prior to study entry
• Over-the-counter (OTC) diet or cold drugs within 14 days before study entry
• Nervous system disorders such as multiple sclerosis, stroke, serious head injury, uncontrolled epilepsy, Tourette's syndrome, Huntington's disease, dementias due to alcohol abuse, vitamin B12 deficiency, syphilis, etc.
• Infections or tumors of the central nervous system
• Any other condition that, in the investigator's opinion, would interfere with the study
• Certain investigational drugs within 30 days before study entry
• Pregnant or breast-feeding
• Allergic to selegiline or the STS patch

California
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Univ of California San Francisco, San Francisco,  California,  94110,  United States
      Univ of California, San Diego, San Diego,  California,  92103,  United States
      Univ of Southern California, Los Angeles,  California,  90033-1079,  United States
      Stanford Univ, Stanford,  California,  94305-5107,  United States
      San Mateo County AIDS Program, Stanford,  California,  94305-5107,  United States
      Willow Clinic, Stanford,  California,  94305-5107,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
Hawaii
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
      The CORE Ctr, Chicago,  Illinois,  60612,  United States
      Cook County Hospital Core Center, Chicago,  Illinois,  60612,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
New York
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States
North Carolina
      Univ of North Carolina, Chapel Hill,  North Carolina,  27514,  United States
Pennsylvania
      Univ of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States
Rhode Island
      The Miriam Hosp, Providence,  Rhode Island,  02906,  United States
      Rhode Island Hosp, Providence,  Rhode Island,  02906,  United States
      Stanley Street Treatment and Resource, Providence,  Rhode Island,  02906,  United States
Texas
      Univ of Texas, Southwestern Med Ctr, Dallas,  Texas,  75235-9173,  United States
Washington
      Univ of Washington, Seattle,  Washington,  98104,  United States

Study chairs or principal investigators

Giovanni Schifitto,  Study Chair
Ned Sacktor,  Study Chair
David Simpson,  Study Chair

Study ID Numbers:  ACTG A5090; AACTG A5090
Record last reviewed:  February 2005
Last Updated:  April 7, 2005
Record first received:  March 22, 2001
ClinicalTrials.gov Identifier:  NCT00013585
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08