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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00013585
• Other study ID #: A5090
• Secondary ID: 10075ACTG A5090A
• Status: Completed
• Phase: Phase 2
• Est. completion date: December 2005

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: December 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognition Disorders
• HIV Infections

Intervention

Drug:
• Selegiline hydrochloride

Locations

Country	Name	City	State
United States	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland
United States	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts
United States	Unc Aids Crs	Chapel Hill	North Carolina
United States	Cook County Hosp. CORE Ctr.	Chicago	Illinois
United States	Northwestern University CRS	Chicago	Illinois
United States	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii
United States	UCLA CARE Center CRS	Los Angeles	California
United States	Beth Israel Med. Ctr., ACTU	New York	New York
United States	Columbia Univ., HIV Prevention and Treatment Medical Ctr.	New York	New York
United States	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania
United States	The Miriam Hosp. ACTG CRS	Providence	Rhode Island
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	Washington U CRS	Saint Louis	Missouri
United States	Ucsd, Avrc Crs	San Diego	California
United States	University of Washington AIDS CRS	Seattle	Washington

Sponsors (3)

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

Country where clinical trial is conducted

United States, 

References & Publications (7)

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

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 — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in cognitive performance Week 24 from screening
Primary	frequencies of adverse experiences, abnormal results on laboratory tests, changes over time in laboratory tests and vital signs
Secondary	Clinical global impression by the investigator comparing selegiline-treated arms with the placebo arm
Secondary	clinical global impression by the subject comparing selegiline-treated arms with the placebo arm
Secondary	cognitive domain-specific scores compared between selegiline-treated arms and the placebo arm
Secondary	neuropsychologic function tests (NPZ-8)
Secondary	fatigue scale (quality of life)
Secondary	markers of immune activation and oxidative stress/apoptosis
Secondary	comparison of selegiline and active metabolite steady-state concentrations at Weeks 4, 12, and 24 to cognitive performance
Secondary	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
Secondary	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

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