Safety and Effectiveness of the Selegiline Patch for Decreased Mental Function in HIV Patients

Study Overview
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Brief Summary
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A decrease in mental function often occurs in patients with HIV. Antiretroviral (ARV) drugs are used to treat this but are not entirely effective. Some other therapy could play a role. The drug selegiline in its 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 the Food and Drug Administration (FDA), to see if it helps with decreased mental function in patients with HIV. 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.

Detailed Description
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Cognitive impairment is a common adverse effect of HIV infection that can progress to dementia. ARVs 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 (CNS) 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 randomly assigned to receive either the STS or 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. Patients on placebo in Step 1 will receive active STS treatment in Step 2. 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.

Official Title
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Phase II, Placebo-Controlled, Double-Blind Study of the Selegiline Transdermal System (STS) in the Treatment of HIV-Associated Cognitive Impairment

Conditions
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Cognition Disorders, HIV Infections

Intervention / Treatment
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* Drug: Selegiline hydrochloride


Participation Criteria
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Eligibility Criteria
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Note: This trial closed to accrual on 12/15/04. Use of the lower-dose STS was discontinued on 05/31/05. Any patients joining the study after 05/31/05 assigned to the interventional arm or who are currently enrolled in Step 2 will receive the higher-dose STS. Inclusion Criteria: HIV infected Stable anti-HIV therapy or no anti-HIV therapy for at least 8 weeks prior to study screening AIDS Dementia Complex Stage of greater than 0 Decreased mental function as shown by tests during screening IQ of 70 or greater Willing to use acceptable methods of contraception during study and for 3 months following study Exclusion Criteria: Tumor involving a large organ or requiring chemotherapy. Patients with basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma are not excluded. Serious mental illness that, in the opinion of the investigator, might interfere with the study Reserpine or meperidine 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 Active symptomatic AIDS-defining opportunistic infection within 30 days prior to 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, or syphilis CNS infections or neoplasms including cytomegalovirus (CMV) encephalitis, toxoplasmosis, primary or metastatic CNS lymphoma, progressive multifocal leukoencephalopathy, cryptococcal or other fungal meningitis, tuberculous CNS infection, or untreated neurosyphilis Any other condition that, in the investigator's opinion, would interfere with the study Certain investigational drugs within 30 days before study entry Allergic to selegiline or the STS patch Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Selegiline hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cognitive performance Week 24 from screening |  |  | 
| frequencies of adverse experiences, abnormal results on laboratory tests, changes over time in laboratory tests and vital signs |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical global impression by the investigator comparing selegiline-treated arms with the placebo arm |  |  | 
| clinical global impression by the subject comparing selegiline-treated arms with the placebo arm |  |  | 
| cognitive domain-specific scores compared between selegiline-treated arms and the placebo arm |  |  | 
| neuropsychologic function tests (NPZ-8) |  |  | 
| fatigue scale (quality of life) |  |  | 
| markers of immune activation and oxidative stress/apoptosis |  |  | 
| comparison of selegiline and active metabolite steady-state concentrations at Weeks 4, 12, and 24 to cognitive performance |  |  | 
| comparison of selegiline and active metabolite steady-state concentrations at Weeks 4, 12, and 24 to historical data in normal volunteers after 7 days of transdermal selegiline administration |  |  | 
| comparison of selegiline and active metabolite steady-state concentrations at Week 4 in subjects on ritonavir-containing protease inhibitor (PI) antiviral regimens, subjects on other PI regimens, and subjects on non-PI-containing antiviral regimens |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive Disorders, AIDS Dementia Complex, Selegiline, Administration, Cutaneous, Neuroprotective Agents