Back to resultsSafety and Effectiveness of the Selegiline "Patch" for Decreased Mental Function in HIV Patients
Primary Purpose
Cognition Disorders, HIV Infections
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Selegiline hydrochloride
Sponsored by
About this trial
This is an interventional treatment trial for Cognition Disorders focused on measuring Cognitive Disorders, AIDS Dementia Complex, Selegiline, Administration, Cutaneous, Neuroprotective Agents
Eligibility 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
Sites / Locations
- UCLA CARE Center CRS
- Ucsd, Avrc Crs
- Univ. of Hawaii at Manoa, Leahi Hosp.
- Northwestern University CRS
- Cook County Hosp. CORE Ctr.
- Johns Hopkins Adult AIDS CRS
- Massachusetts General Hospital ACTG CRS
- Washington U CRS
- Beth Israel Med. Ctr., ACTU
- Columbia Univ., HIV Prevention and Treatment Medical Ctr.
- Univ. of Rochester ACTG CRS
- Unc Aids Crs
- Hosp. of the Univ. of Pennsylvania CRS
- The Miriam Hosp. ACTG CRS
- University of Washington AIDS CRS
Outcomes
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
Full Information
NCT ID
NCT00013585
First Posted
March 22, 2001
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Neurologic AIDS Research Consortium (NARC)
1. Study Identification
Unique Protocol Identification Number
NCT00013585
Brief Title
Safety and Effectiveness of the Selegiline "Patch" for Decreased Mental Function in HIV Patients
Official Title
Phase II, Placebo-Controlled, Double-Blind Study of the Selegiline Transdermal System (STS) in the Treatment of HIV-Associated Cognitive Impairment
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 2005 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators
National Institute of Neurological Disorders and Stroke (NINDS), Neurologic AIDS Research Consortium (NARC)
4. Oversight
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cognition Disorders, HIV Infections
Keywords
Cognitive Disorders, AIDS Dementia Complex, Selegiline, Administration, Cutaneous, Neuroprotective Agents
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
127 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Selegiline hydrochloride
Primary Outcome Measure Information:
Title
Change in cognitive performance Week 24 from screening
Title
frequencies of adverse experiences, abnormal results on laboratory tests, changes over time in laboratory tests and vital signs
Secondary Outcome Measure Information:
Title
Clinical global impression by the investigator comparing selegiline-treated arms with the placebo arm
Title
clinical global impression by the subject comparing selegiline-treated arms with the placebo arm
Title
cognitive domain-specific scores compared between selegiline-treated arms and the placebo arm
Title
neuropsychologic function tests (NPZ-8)
Title
fatigue scale (quality of life)
Title
markers of immune activation and oxidative stress/apoptosis
Title
comparison of selegiline and active metabolite steady-state concentrations at Weeks 4, 12, and 24 to cognitive performance
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giovanni Schifitto, M.D.
Organizational Affiliation
Department of Neurology, University of Rochester Medical Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ned Sacktor, M.D.
Organizational Affiliation
Department of Neurology, Johns Hopkins University Bayview Medical Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
David Simpson, M.D.
Organizational Affiliation
Department of Clinical Neurophysiology, Mount Sinai School of Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
UCLA CARE Center CRS
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Ucsd, Avrc Crs
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Univ. of Hawaii at Manoa, Leahi Hosp.
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96816
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cook County Hosp. CORE Ctr.
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Beth Israel Med. Ctr., ACTU
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Columbia Univ., HIV Prevention and Treatment Medical Ctr.
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Facility Name
Hosp. of the Univ. of Pennsylvania CRS
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
The Miriam Hosp. ACTG CRS
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02906
Country
United States
Facility Name
University of Washington AIDS CRS
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
15569045
Citation
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.
Results Reference
background
PubMed Identifier
14697901
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. doi: 10.1016/S0161-813X(03)00105-0.
Results Reference
background
PubMed Identifier
15579274
Citation
McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004 Dec;157(1-2):3-10. doi: 10.1016/j.jneuroim.2004.08.042.
Results Reference
background
PubMed Identifier
10636157
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. doi: 10.1212/wnl.54.1.233.
Results Reference
background
PubMed Identifier
11171916
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. doi: 10.1212/wnl.56.3.415.
Results Reference
background
PubMed Identifier
18042509
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 impairment: open-label report of ACTG 5090. HIV Clin Trials. 2007 Nov-Dec;8(6):437-46. doi: 10.1310/hct0806-437.
Results Reference
result
PubMed Identifier
21181521
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.
Results Reference
result
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Safety and Effectiveness of the Selegiline "Patch" for Decreased Mental Function in HIV Patients
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