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Imaging CRF X NOP Interactions in Alcohol Use Disorder

1. juni 2026 oppdatert av: Rajesh Narendran

Does a Hyperactive Nociceptin Opioid Peptide Receptor System Promote Relapse in Heavy Drinking AUD Subjects: a [C-11]NOP-1A and Hydrocortisone PET Study

This positron emission tomography imaging study uses [C-11]NOP-1A and hydrocortisone to image stress-modulating proteins in heavy drinking alcohol use disorder (AUD) subjects and healthy controls (HC). It will also characterize the role of these stress-regulating proteins in a relapse to alcohol.

Studieoversikt

Detaljert beskrivelse

Hydrocortisone administration leads to a 10 to 15% increase in [11C]NOP-1A VT in brain regions, including the amygdala. Increased NOP measured in response to cortisol, and by extension, corticotrophin-releasing factor (CRF), in this paradigm reflects an individual's ability to enhance N/OFQ transmission during stress. Here, the investigators propose to use this novel imaging paradigm to compare hydrocortisone-induced increases in [11C]NOP-1A binding (DVT) in the amygdala (and secondary reward regions) in heavy drinking AUD subjects Vs. HC. The hypothesis that hydrocortisone-induced increases in [11C]NOP-1A binding (DVT) will be larger in heavy drinking AUD relative to HC (aim 1), and this will predict relapse to alcohol (aim 2). Such a result will support the presence of a hyperactive NOP receptor system in response to increases in cortisol/CRF during conditions such as stress, chronic pain, etc., promoting relapse in heavy drinking AUD subjects.

Studietype

Intervensjonell

Registrering (Antatt)

90

Fase

  • Tidlig fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studiesteder

    • Pennsylvania
      • Pittsburgh, Pennsylvania, Forente stater, 15213
        • Rekruttering
        • University of Pittsburgh

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

  • Voksen

Tar imot friske frivillige

Ja

Beskrivelse

Heavy drinking alcohol use disorder subjects (AUD)

  1. Males or females between 18 and 55 years old
  2. fulfill DSM-5 criteria for moderate or severe ( > or = 4 criteria) alcohol use disorder
  3. fulfill both NIAAA heavy drinking91 (consuming for males > or = 5 drinks on any day; for females > or = 4 drinks on any day) and WHO high-risk/very high-risk drinking level criteria66 (for males > or = 30 drinks/week; for females > or = 20 drinks/week) in the past four weeks prior to enrollment
  4. No lifetime DSM-5 psychiatric disorders, including schizophrenia, schizoaffective disorder, bipolar disorder, or developmental disorders.
  5. No comorbid current DSM-5 depressive or anxiety disorders
  6. No other current DSM-5 substance use disorders, including opioids, cocaine, amphetamines, sedative-hypnotics, hallucinogens, and inhalants. Subjects with current moderate and severe DSM-5 cannabis use disorder will also be excluded
  7. Not currently on psychotropic medications that can directly (e.g., buprenorphine) or indirectly influence binding to NOP (e.g., medications that alter dopamine, GABA, glutamate, etc.) or modify alcohol consumption patterns (e.g., naltrexone, acamprosate, disulfiram);
  8. No regular use of medical medications that can potentially interact with hydrocortisone (other corticosteroids, mifepristone, etc.) or increase the risks associated with arterial line removal (warfarin, clopidogrel, aspirin, naproxen, ibuprofen, etc.)
  9. No clinically significant medical or neurological illnesses, including a history of immune compromise, HPA-axis dysfunction, Cushing's syndrome, glaucoma, morbid obesity, severe hyperglycemia, and hyperlipidemia, all of which are contraindications for hydrocortisone
  10. No history of anemia or history of deep vein thrombosis, pulmonary embolism, thrombocytopenia or thrombocytosis
  11. Not currently pregnant or breast-feeding
  12. No history of complicated alcohol withdrawal symptoms such as seizures, alcoholic hallucinosis, delirium tremens, or required admission to an inpatient detox program to prevent such symptoms
  13. Not currently employed as a radiation worker or has participated in a radiation-related research protocol within the previous year such that the total cumulative annual radiation dose (i.e., from participation in previous radioactive drug studies and this study) would exceed the radiation dose limits specified in the FDA regulations (i.e., 21 CFR 361.1) that govern the research use of radiotracers
  14. No metallic objects in the body that are contraindicated for MRI.

Healthy Control subjects (HC)

  1. Males or females between 18 and 55 years old
  2. No DSM-5 psychiatric or substance use disorders other than tobacco use disorder
  3. No NIAAA heavy drinking in the past year (> or = 5 drinks on any day or more than 14 drinks per week for males; > or = 4 drinks on any day or more than 7 drinks per week for females)
  4. 7 to 14 above.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Grunnvitenskap
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: KJÆLEDYR
[C-11]NOP-1A
Radiotracer
Intravenous, 1 mg/Kg
Radiotracer

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Amygdala DELTA VT
Tidsramme: Baseline/pre hydrocortisone, and 3-hours post hydrocortisone
VT is the volume of distribution expressed relative to total plasma radioligand concentration; DELTA VT is the change from baseline to post-hydrocortisone
Baseline/pre hydrocortisone, and 3-hours post hydrocortisone
Total number of negative ETG tests
Tidsramme: over 8-week follow-up
Represents level of abstinence in contingency management
over 8-week follow-up

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Midbrain DELTA VT
Tidsramme: Baseline/pre hydrocortisone and 3-hours post hydrocortisone
VT is the volume of distribution expressed relative to total plasma radioligand
Baseline/pre hydrocortisone and 3-hours post hydrocortisone
Ventral striatum DELTA VT
Tidsramme: Baseline/pre hydrocortisone and 3-hours post hydrocortisone
VT is the volume of distribution expressed relative to total plasma radioligand
Baseline/pre hydrocortisone and 3-hours post hydrocortisone
Orbitofrontal Cortex DELTA VT
Tidsramme: Baseline/pre hydrocortisone and 3-hours post hydrocortisone
VT is the volume of distribution expressed relative to total plasma radioligand
Baseline/pre hydrocortisone and 3-hours post hydrocortisone
Relapse to alcohol
Tidsramme: over 8-weeks follow up
Abstained; Relapsed; Drop-out
over 8-weeks follow up
Relapse to alcohol severity (self-reported)
Tidsramme: over 8- week follow up
Heavy drinking days/week and Abstinent days/week
over 8- week follow up

Andre resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Perceived Stress Scale
Tidsramme: over 8-week follow up
mean and peak scores during follow-up
over 8-week follow up
Penn Alcohol Craving Scale
Tidsramme: over 8-week follow up
mean and peak score during follow up
over 8-week follow up
Plasma cortisol
Tidsramme: Baseline/pre hydrocortisone and post-hydrocortisone
Plasma cortisol measured in blood
Baseline/pre hydrocortisone and post-hydrocortisone

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

  • Hovedetterforsker: Rajesh Narendran, University of Pittsburgh

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. juni 2026

Primær fullføring (Antatt)

30. juni 2031

Studiet fullført (Antatt)

30. juni 2032

Datoer for studieregistrering

Først innsendt

16. mai 2026

Først innsendt som oppfylte QC-kriteriene

22. mai 2026

Først lagt ut (Faktiske)

29. mai 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

3. juni 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

1. juni 2026

Sist bekreftet

1. juni 2026

Mer informasjon

Begreper knyttet til denne studien

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

JA

IPD-planbeskrivelse

All individual participant data that underlie the results reported in the publication or upon study completion will be shared after de-identification via the NIAAA Data Archive

IPD-delingstidsramme

Upon publication or study completion. Data will be available indefinitely on the data archives

Tilgangskriterier for IPD-deling

Available as per the NIAAA Data Archive repository criteria for access

IPD-deling Støtteinformasjonstype

  • STUDY_PROTOCOL

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

produkt produsert i og eksportert fra USA

Nei

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