- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT03244488
Mental Ability Challenge Study in Adults With and Without HIV
21. februar 2019 opdateret af: Asante Kamkwalala, Vanderbilt University Medical Center
Cholinergic Correlates of Impaired Cognitive Ability in HIV-Associated Neurocognitive Disorders
It is estimated that by 2016, nearly 50% of HIV-positive individuals in the US will be aged 50 or older, and up to 60% of those will experience some degree of cognitive impairment as they age.
The purpose of this study is to evaluate the contribution of the neuronal cholinergic receptor system to the cognitive impairments seen in adults aging with chronic HIV Infection.
By using anti-cholinergic challenge drugs to reversibly "stress" cognitive functioning, the investigators hope to understand whether the presence of the HIV virus in the brain impairs the neural system necessary for normal cognition, more than would be expected from normal cognitive aging.
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
This study is intended to evaluate the involvement of the neuronal cholinergic receptor system in the accelerated cognitive aging profile seen in adults living with chronic HIV-1 infection.
It is estimated by the CDC that by the year 2016, nearly 50% of the US' HIV-positive population will be 50 or older.
The HIV-1 virus is known to enter the CNS very rapidly after initial infection, and cause a pattern of persistent neural inflammation, which is deleterious to neurons and glia.
This damage is believed to be the basis of cognitive impairment associated with long-term chronic HIV infection, known as HIV-Associated Neurocognitive Disorders (HAND).
Successful introduction of Anti-Retroviral Treatment (ART) has greatly reduced the likelihood of progressing to the most severe category of HAND (HIV-Associated Dementia), however the mild and moderate forms (Asymptomatic Neurocognitive Impairment and Mild Neurocognitive Disorder, respectively) are still fairly common even in adults declared "virally suppressed", with little to no detectable peripheral viral DNA/RNA.
Prior studies have shown that over the lifetime, more than 50% of adults diagnosed with HIV will experience some degree of cognitive impairment as they age.
Some of these changes may be due to cholinergic dysfunction.
The acetylcholinergic receptor system is necessary for normal cognitive performance, and is active during working memory, executive functioning, attention, and learning tasks.
It has been shown that as the human brain ages, cognitive ability begins to decline, and correlates with declining acetylcholinergic activity.
The cholinergic theory of cognitive aging postulates that this loss of activity at cholinergic receptors with age is at least partly responsible for poorer cognitive performance in aging.
I will use this model to examine the impact of HIV infection on cholinergic system functioning.
This study will use a well-established anti-cholinergic drug challenge model to evaluate cognitive performance in domains of cognitive functioning relevant to cholinergic functioning.
Under conditions of temporary muscarinic or nicotinic blockade, or a combination of both, I aim to explore the contribution of putative cholinergic receptor dysfunction to the observed symptoms of HAND.
I also intend to determine whether age and HIV-status interact to produce an accelerated pattern of cholinergic cognitive aging that would indicate that older adults with HIV are at higher risk for more rapid cognitive aging than HIV-negative individuals.
If successful, the outcome of this study would support the future exploration of novel pro-cholinergic medications to treat cognitive symptoms of HAND, which may improve quality of life for adults living with chronic HIV infection, as they survive into old age.
Undersøgelsestype
Observationel
Tilmelding (Faktiske)
22
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
-
-
Tennessee
-
Nashville, Tennessee, Forenede Stater, 37212
- Vanderbilt University Medical Center
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
35 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ja
Køn, der er berettiget til at studere
Alle
Prøveudtagningsmetode
Ikke-sandsynlighedsprøve
Studiebefolkning
HIV-Positive Healthy older adults and HIV-Negative Healthy older adults
Beskrivelse
Inclusion Criteria:
- 35 years of age or older;
- HIV-Positive (must be on ART's for at least 6 months, most recent viral load (within 6 months) <50, CD4+ count >200, must be diagnosed HIV-positive at least 5 years) or HIV-Negative, At-Risk Individuals
- Able and willing to give written informed consent
- Negative urine pregnancy test
- Adequate visual and auditory acuity to allow neuropsychological testing.
Exclusion Criteria:
- Unmanaged HIV Infection, identified by no current medication regimen or the presence of one or more AIDS-defining conditions
- Fagerstrom cigarettes per day (CPD) score of '2' indicating heavy use of nicotine
- An ART regimen including a Protease Inhibitor Medication
- A documented history of cardiac disease or abnormal ECG at Screening
- Current alcohol or substance abuse, particularly intravenously
- Current use of psychoactive medications (antipsychotics, benzodiazepines, etc.)
- Current Axis I or Axis II psychiatric disorder
- History of myocardial infarction in the past year or unstable or severe cardiovascular disease
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
Kohorter og interventioner
Gruppe / kohorte |
Intervention / Behandling |
---|---|
HIV-Positive
Patients will be administered each of 4 possible treatments: high dose (5 mcg/kg) scopolamine, high dose (20 mg) mecamylamine, a low dose combination (2.5mcg/kg and 10 mg) of scopolamine and mecamylamine, or placebo.
|
2.5 or 5 mcg/kg of scopolamine via IV
10 or 20mg of mecamylamine orally
|
HIV-Negative
Patients will be administered each of 4 possible treatments: high dose (5 mcg/kg) scopolamine, high dose (20 mg) mecamylamine, a low dose combination (2.5mcg/kg and 10 mg) of scopolamine and mecamylamine, or placebo.
|
2.5 or 5 mcg/kg of scopolamine via IV
10 or 20mg of mecamylamine orally
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Cognitive Outcome - Lower verbal memory score
Tidsramme: 2 hours
|
Cognitive performance will be more significantly impaired by study medications in HIV-positive participants relative to HIV-negative participants, indicating impairment of cholinergic neurotransmitter system.
|
2 hours
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Age and HIV-Status Interaction - Slower CRTreaction time
Tidsramme: 2 hours
|
Older age and positive HIV status will interact to more significantly impair cognitive performance as measured by reaction time on the Choice Reaction Time task under the influence of study medications, than either variable alone.
|
2 hours
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Faktiske)
1. december 2015
Primær færdiggørelse (Faktiske)
1. december 2018
Studieafslutning (Faktiske)
1. december 2018
Datoer for studieregistrering
Først indsendt
27. juli 2017
Først indsendt, der opfyldte QC-kriterier
4. august 2017
Først opslået (Faktiske)
9. august 2017
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
25. februar 2019
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
21. februar 2019
Sidst verificeret
1. februar 2019
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Psykiske lidelser
- Hjernesygdomme
- Sygdomme i centralnervesystemet
- Sygdomme i nervesystemet
- RNA-virusinfektioner
- Virussygdomme
- Infektioner
- Blodbårne infektioner
- Overførbare sygdomme
- Seksuelt overførte sygdomme, virale
- Seksuelt overførte sygdomme
- Lentivirus infektioner
- Retroviridae infektioner
- Immunologiske mangelsyndromer
- Sygdomme i immunsystemet
- Neurokognitive lidelser
- Demens
- HIV-infektioner
- AIDS demenskompleks
- Aldring, for tidligt
- Lægemidlers fysiologiske virkninger
- Neurotransmittermidler
- Molekylære mekanismer for farmakologisk virkning
- Antihypertensive midler
- Parasympatholytika
- Autonome agenter
- Agenter fra det perifere nervesystem
- Muskarine antagonister
- Kolinerge antagonister
- Kolinerge midler
- Antiemetika
- Gastrointestinale midler
- Adjuvanser, anæstesi
- Mydriatics
- Ganglionblokkere
- Nikotiniske antagonister
- Mecamylamin
- Scopolamin
- Butylscopolammoniumbromid
Andre undersøgelses-id-numre
- 150929
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ja
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
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