Cognition DisordersPhase 2NCT00013585
Safety and Effectiveness of the Selegiline "Patch" for Decreased Mental Function in HIV Patients
A Phase 2 study testing Selegiline hydrochloride in people with Cognition Disorders and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cognition Disorders, HIV Infections
- What is being tested?
- Selegiline hydrochloride
- How many people
- 127 participants
- Where
- 15 sitesUnited States
- Study dates
- Start not givento Dec 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, 02114
Unc Aids Crs
Chapel Hill, North Carolina, 27514
Northwestern University CRS
Chicago, Illinois, 60611
Cook County Hosp. CORE Ctr.
Chicago, Illinois, 60612
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816
UCLA CARE Center CRS
Los Angeles, California, 90095
Beth Israel Med. Ctr., ACTU
New York, New York, 10003
Columbia Univ., HIV Prevention and Treatment Medical Ctr.
New York, New York, 10032
Hosp. of the Univ. of Pennsylvania CRS
Philadelphia, Pennsylvania, 19104
The Miriam Hosp. ACTG CRS
Providence, Rhode Island, 02906
Univ. of Rochester ACTG CRS
Rochester, New York, 14642
Ucsd, Avrc Crs
San Diego, California, 92103
University of Washington AIDS CRS
Seattle, Washington, 98104
Washington U CRS
St Louis, Missouri
About this study
Official title: 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.
Read the 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.
- Conditions
- Cognition Disorders, HIV Infections
- Being tested
- Selegiline hydrochloride
- Keywords
- Cognitive Disorders, AIDS Dementia Complex, Selegiline, Administration, Cutaneous, Neuroprotective Agents
- Medical subject headings
- Cognition Disorders, HIV Infections, Cognitive Dysfunction, AIDS Dementia Complex
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Selegiline hydrochlorideDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (9)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Cognition DisordersStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Neurologic AIDS Research Consortium (NARC)
- Responsible party
- Sponsor
- Investigators
- Giovanni Schifitto, M.D., Study chair, Department of Neurology, University of Rochester Medical CenterNed Sacktor, M.D., Study chair, Department of Neurology, Johns Hopkins University Bayview Medical CenterDavid Simpson, M.D., Study chair, Department of Clinical Neurophysiology, Mount Sinai School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00013585
- Sponsor's protocol ID
- A5090
- Other IDs
- 10075, ACTG A5090, AACTG A5090
- Status last verified
- Oct 2021
- First submitted
- 22 Mar 2001
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
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.
PubMed 15569045Koutsilieri 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.
PubMed 14697901McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004 Dec;157(1-2):3-10. doi: 10.1016/j.jneuroim.2004.08.042.
PubMed 15579274Sacktor 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.
PubMed 10636157Schifitto 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.
PubMed 11171916Evans 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.
PubMed 18042509Schifitto 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.
PubMed 21181521
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Placebo-Controlled, Double-Blind Study of the Selegiline Transdermal System (STS) in the Treatment of HIV-Associated Cognitive Impairment
- ClinicalTrials.gov ID
- NCT00013585
- Acronym / sponsor ID
- A5090
- Conditions
- Cognition Disorders, HIV Infections
- Keywords
- Cognitive Disorders, AIDS Dementia Complex, Selegiline, Administration, Cutaneous, Neuroprotective Agents
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Neurologic AIDS Research Consortium (NARC)
- Study completion
- Dec 2005 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Selegiline hydrochloride | Drug | – |
Primary outcome
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
9 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Background: PubMed 15569045Bell 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.
- Background: PubMed 14697901Koutsilieri 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.
- Background: PubMed 15579274McArthur JC. HIV dementia: an evolving disease. J Neuroimmunol. 2004 Dec;157(1-2):3-10. doi: 10.1016/j.jneuroim.2004.08.042.
- Background: PubMed 10636157Sacktor 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.
- Background: PubMed 11171916Schifitto 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 publication: PubMed 18042509Evans 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 publication: PubMed 21181521Schifitto 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.
Related trials for Cognition Disorders
Recruiting
Metabolic Health, Bones and Nuts During Weight Loss in Adults
Weight Loss, Bone Density
Not yet recruitingPhase 2
Lisdexamfetamine For the Treatment of Conduct Disorder in Children
Conduct Disorder
Recruiting
HEARS-NPS: Addressing Hearing Loss as a Common Unmet Contributor of Neuropsychiatric Symptoms
Alzheimer Disease, Dementia
RecruitingObservational study
Locus Coeruleus and CCHS (Congenital Central Hypoventilation Syndrome)
Ondine Syndrome (Congenital Central Hypoventilation Syndrome)
RecruitingPhase 1
PET Imaging of Phosphodiesterase-4 (PDE4) in Volunteers With Alzheimer Disease (AD) or Mild Cognitive Impairment (MCI)
Alzheimer s Disease, Mild Cognitive Impairment
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giovanni Schifitto, M.D. study chair
Department of Neurology, University of Rochester Medical Center
Ned Sacktor, M.D. study chair
Department of Neurology, Johns Hopkins University Bayview Medical Center
David Simpson, M.D. study chair
Department of Clinical Neurophysiology, Mount Sinai School of Medicine
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Selegiline hydrochloride in people with Cognition Disorders and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in cognitive performance Week 24 from screening. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00013585, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.