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

NCT ID: NCT00013585

Last Updated: 2021-11-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

127 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2005-12-31

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.

Conditions

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Cognition Disorders HIV Infections

Keywords

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Cognitive Disorders AIDS Dementia Complex Selegiline Administration, Cutaneous Neuroprotective Agents

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Interventions

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Selegiline hydrochloride

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Neurologic AIDS Research Consortium (NARC)

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Giovanni Schifitto, M.D.

Role: STUDY_CHAIR

Department of Neurology, University of Rochester Medical Center

Ned Sacktor, M.D.

Role: STUDY_CHAIR

Department of Neurology, Johns Hopkins University Bayview Medical Center

David Simpson, M.D.

Role: STUDY_CHAIR

Department of Clinical Neurophysiology, Mount Sinai School of Medicine

Locations

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UCLA CARE Center CRS

Los Angeles, California, United States

Site Status

Ucsd, Avrc Crs

San Diego, California, United States

Site Status

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Cook County Hosp. CORE Ctr.

Chicago, Illinois, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

Beth Israel Med. Ctr., ACTU

New York, New York, United States

Site Status

Columbia Univ., HIV Prevention and Treatment Medical Ctr.

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Site Status

The Miriam Hosp. ACTG CRS

Providence, Rhode Island, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Bell JE. An update on the neuropathology of HIV in the HAART era. Histopathology. 2004 Dec;45(6):549-59. doi: 10.1111/j.1365-2559.2004.02004.x.

Reference Type BACKGROUND
PMID: 15569045 (View on PubMed)

Koutsilieri E, Scheller C, ter Meulen V, Riederer P. Monoamine oxidase inhibition and CNS immunodeficiency infection. Neurotoxicology. 2004 Jan;25(1-2):267-70. doi: 10.1016/S0161-813X(03)00105-0.

Reference Type BACKGROUND
PMID: 14697901 (View on PubMed)

McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004 Dec;157(1-2):3-10. doi: 10.1016/j.jneuroim.2004.08.042.

Reference Type BACKGROUND
PMID: 15579274 (View on PubMed)

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. doi: 10.1212/wnl.54.1.233.

Reference Type BACKGROUND
PMID: 10636157 (View on PubMed)

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. doi: 10.1212/wnl.56.3.415.

Reference Type BACKGROUND
PMID: 11171916 (View on PubMed)

Evans SR, Yeh TM, Sacktor N, Clifford DB, Simpson D, Miller EN, Ellis RJ, Valcour V, Marra CM, Millar L, Schifitto G; AIDS Clinical Trials Group and the Neurologic AIDS Research Consortium. Selegiline transdermal system (STS) for HIV-associated cognitive impairment: open-label report of ACTG 5090. HIV Clin Trials. 2007 Nov-Dec;8(6):437-46. doi: 10.1310/hct0806-437.

Reference Type RESULT
PMID: 18042509 (View on PubMed)

Schifitto G, Deng L, Yeh TM, Evans SR, Ernst T, Zhong J, Clifford D. Clinical, laboratory, and neuroimaging characteristics of fatigue in HIV-infected individuals. J Neurovirol. 2011 Feb;17(1):17-25. doi: 10.1007/s13365-010-0010-5. Epub 2010 Dec 23.

Reference Type RESULT
PMID: 21181521 (View on PubMed)

Other Identifiers

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10075

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5090

Identifier Type: -

Identifier Source: secondary_id

AACTG A5090

Identifier Type: -

Identifier Source: secondary_id

A5090

Identifier Type: -

Identifier Source: org_study_id