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Imaging CRF X NOP Interactions in Alcohol Use Disorder

1. juni 2026 opdateret af: 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.

Studieoversigt

Detaljeret 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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

90

Fase

  • Tidlig fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

Studiesteder

    • Pennsylvania
      • Pittsburgh, Pennsylvania, Forenede Stater, 15213
        • Rekruttering
        • University of Pittsburgh

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

  • Voksen

Tager imod sunde 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

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Grundvidenskab
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: KÆLEDYR
[C-11]NOP-1A
Radiotracer
Intravenous, 1 mg/Kg
Radiotracer

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
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
Foranstaltningsbeskrivelse
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

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Efterforskere

  • Ledende efterforsker: Rajesh Narendran, University of Pittsburgh

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. juni 2026

Primær færdiggørelse (Anslået)

30. juni 2031

Studieafslutning (Anslået)

30. juni 2032

Datoer for studieregistrering

Først indsendt

16. maj 2026

Først indsendt, der opfyldte QC-kriterier

22. maj 2026

Først opslået (Faktiske)

29. maj 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

3. juni 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

1. juni 2026

Sidst verificeret

1. juni 2026

Mere information

Begreber relateret til denne undersøgelse

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (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

IPD-delingsadgangskriterier

Available as per the NIAAA Data Archive repository criteria for access

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

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