- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT03244488
Mental Ability Challenge Study in Adults With and Without HIV
21. februar 2019 oppdatert av: 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.
Studieoversikt
Status
Fullført
Forhold
Intervensjon / Behandling
Detaljert 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.
Studietype
Observasjonsmessig
Registrering (Faktiske)
22
Kontakter og plasseringer
Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.
Studiesteder
-
-
Tennessee
-
Nashville, Tennessee, Forente stater, 37212
- Vanderbilt University Medical Center
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-
Deltakelseskriterier
Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
35 år og eldre (Voksen, Eldre voksen)
Tar imot friske frivillige
Ja
Kjønn som er kvalifisert for studier
Alle
Prøvetakingsmetode
Ikke-sannsynlighetsprøve
Studiepopulasjon
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
Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.
Hvordan er studiet utformet?
Designdetaljer
Kohorter og intervensjoner
Gruppe / Kohort |
Intervensjon / 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
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
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 |
Tiltaksbeskrivelse |
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
|
Samarbeidspartnere og etterforskere
Det er her du vil finne personer og organisasjoner som er involvert i denne studien.
Studierekorddatoer
Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.
Studer hoveddatoer
Studiestart (Faktiske)
1. desember 2015
Primær fullføring (Faktiske)
1. desember 2018
Studiet fullført (Faktiske)
1. desember 2018
Datoer for studieregistrering
Først innsendt
27. juli 2017
Først innsendt som oppfylte QC-kriteriene
4. august 2017
Først lagt ut (Faktiske)
9. august 2017
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
25. februar 2019
Siste oppdatering sendt inn som oppfylte QC-kriteriene
21. februar 2019
Sist bekreftet
1. februar 2019
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Psykiske lidelser
- Hjernesykdommer
- Sykdommer i sentralnervesystemet
- Sykdommer i nervesystemet
- RNA-virusinfeksjoner
- Virussykdommer
- Infeksjoner
- Blodbårne infeksjoner
- Smittsomme sykdommer
- Seksuelt overførbare sykdommer, virale
- Seksuelt overførbare sykdommer
- Lentivirus infeksjoner
- Retroviridae-infeksjoner
- Immunologiske mangelsyndromer
- Sykdommer i immunsystemet
- Nevrokognitive lidelser
- Demens
- HIV-infeksjoner
- AIDS demenskompleks
- Aldring, for tidlig
- Fysiologiske effekter av legemidler
- Nevrotransmittere agenter
- Molekylære mekanismer for farmakologisk virkning
- Antihypertensive midler
- Parasympatholytika
- Autonome agenter
- Agenter fra det perifere nervesystemet
- Muskariniske antagonister
- Kolinerge antagonister
- Kolinerge midler
- Antiemetika
- Gastrointestinale midler
- Adjuvanser, anestesi
- Mydriatics
- Ganglionblokkere
- Nikotiniske antagonister
- Mecamylamin
- Skopolamin
- Butylskopolammoniumbromid
Andre studie-ID-numre
- 150929
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
NEI
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Ja
Studerer et amerikansk FDA-regulert enhetsprodukt
Nei
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