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

Condition(s) targeted: Cognition Disorders; HIV Infections

Intervention: Selegiline hydrochloride (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Giovanni Schifitto, M.D., Study Chair, Affiliation: Department of Neurology, University of Rochester Medical Center
Ned Sacktor, M.D., Study Chair, Affiliation: Department of Neurology, Johns Hopkins University Bayview Medical Center
David Simpson, M.D., Study Chair, Affiliation: Department of Clinical Neurophysiology, Mount Sinai School of Medicine

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.

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

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome:

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:

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

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

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

Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States

Univ of Hawaii, Honolulu, Hawaii 96816, United States

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

Johns Hopkins Hosp, Baltimore, Maryland 21287, United States

Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States

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

Univ of North Carolina, Chapel Hill, North Carolina 27514, United States

Univ of Pennsylvania, Philadelphia, Pennsylvania 19104, United States

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

Univ of Texas, Southwestern Med Ctr, Dallas, Texas 75235-9173, United States

Univ of Washington, Seattle, Washington 98104, United States

Haga clic aquí para ver información sobre este ensayo clínico en español.

Related publications:

Bell JE. An update on the neuropathology of HIV in the HAART era. Histopathology. 2004 Dec;45(6):549-59. Review.

Koutsilieri E, Scheller C, ter Meulen V, Riederer P. Monoamine oxidase inhibition and CNS immunodeficiency infection. Neurotoxicology. 2004 Jan;25(1-2):267-70. Review.

McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004 Dec;157(1-2):3-10. Review.

Sacktor N, Schifitto G, McDermott MP, Marder K, McArthur JC, Kieburtz K. Transdermal selegiline in HIV-associated cognitive impairment: pilot, placebo-controlled study. Neurology. 2000 Jan 11;54(1):233-5.

Schifitto G, Kieburtz K, McDermott MP, McArthur J, Marder K, Sacktor N, Palumbo D, Selnes O, Stern Y, Epstein L, Albert S. Clinical trials in HIV-associated cognitive impairment: cognitive and functional outcomes. Neurology. 2001 Feb 13;56(3):415-8.

Last updated: January 31, 2008