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

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

127

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (ACTUAL)

December 1, 2005

Study Registration Dates

First Submitted

March 22, 2001

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ACTUAL)

November 1, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A5090
  • 10075 (Other Identifier: CTEP)
  • ACTG A5090
  • AACTG A5090

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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