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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00013585

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH), Neurologic AIDS Research Consortium (NARC) (Other)

127

Enrollment

Locations

8.5

Patients Per Site

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cognition Disorders HIV Infections	Drug: Selegiline hydrochloride	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

127 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

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

Actual Study Completion Date :

Dec 1, 2005

Outcome Measures

Primary Outcome Measures

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

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA CARE Center CRS	Los Angeles	California	United States	90095
2	Ucsd, Avrc Crs	San Diego	California	United States	92103
3	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
4	Northwestern University CRS	Chicago	Illinois	United States	60611
5	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
6	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
7	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
8	Washington U CRS	Saint Louis	Missouri	United States
9	Beth Israel Med. Ctr., ACTU	New York	New York	United States	10003
10	Columbia Univ., HIV Prevention and Treatment Medical Ctr.	New York	New York	United States	10032
11	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
12	Unc Aids Crs	Chapel Hill	North Carolina	United States	27514
13	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
14	The Miriam Hosp. ACTG CRS	Providence	Rhode Island	United States	02906
15	University of Washington AIDS CRS	Seattle	Washington	United States	98104

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Neurological Disorders and Stroke (NINDS)
Neurologic AIDS Research Consortium (NARC)

Investigators

Study Chair: Giovanni Schifitto, M.D., Department of Neurology, University of Rochester Medical Center
Study Chair: Ned Sacktor, M.D., Department of Neurology, Johns Hopkins University Bayview Medical Center
Study Chair: David Simpson, M.D., Department of Clinical Neurophysiology, Mount Sinai School of Medicine