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RecruitingNCT07612631Updated Jun 3, 2026

Imaging CRF X NOP Interactions in Alcohol Use Disorder

An Early Phase 1 interventional study of Baseline [C-11]NOP-1A PET scan and Hydrocortisone in Alcohol Use Disorder, sponsored by Rajesh Narendran. Recruiting at 1 site in United States. Open to participants aged 18 Years to 55 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-03.

Sponsored by Rajesh Narendran · Early Phase 1, Interventional, and Basic science

Phase
Early Phase 1
Study type
Interventional
Enrollment
90
Allocation
Not applicable
Ages
18 Years to 55 Years
Sex
All
01

Study summary

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.

Read the detailed description

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.

02

Conditions studied

  • Alcohol Use Disorder

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Keywords

  • [C-11]NOP-1A PET
  • Nociceptive opioid peptide receptor
03

Who can participate

Ages eligible
18 Years to 55 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Eligibility criteria

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.
04

Study design

Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
90 participants (estimated)

Study arms

  • Experimental
    PET

    \[C-11\]NOP-1A

    Radiation: Baseline [C-11]NOP-1A PET scan · Drug: Hydrocortisone · Radiation: Post-hydrocortisone [C-11]NOP-1A PET scan

Interventions

  • RadiationBaseline [C-11]NOP-1A PET scan

    Radiotracer

  • DrugHydrocortisone

    Intravenous, 1 mg/Kg

  • RadiationPost-hydrocortisone [C-11]NOP-1A PET scan

    Radiotracer

05

What researchers measure

Primary outcomes

  1. Amygdala DELTA VT

    VT is the volume of distribution expressed relative to total plasma radioligand concentration; DELTA VT is the change from baseline to post-hydrocortisone

    Time frame: Baseline/pre hydrocortisone, and 3-hours post hydrocortisone

  2. Total number of negative ETG tests

    Represents level of abstinence in contingency management

    Time frame: over 8-week follow-up

Secondary outcomes

  1. Midbrain DELTA VT

    VT is the volume of distribution expressed relative to total plasma radioligand

    Time frame: Baseline/pre hydrocortisone and 3-hours post hydrocortisone

  2. Ventral striatum DELTA VT

    VT is the volume of distribution expressed relative to total plasma radioligand

    Time frame: Baseline/pre hydrocortisone and 3-hours post hydrocortisone

  3. Orbitofrontal Cortex DELTA VT

    VT is the volume of distribution expressed relative to total plasma radioligand

    Time frame: Baseline/pre hydrocortisone and 3-hours post hydrocortisone

  4. Relapse to alcohol

    Abstained; Relapsed; Drop-out

    Time frame: over 8-weeks follow up

  5. Relapse to alcohol severity (self-reported)

    Heavy drinking days/week and Abstinent days/week

    Time frame: over 8- week follow up

Other outcomes

  1. Perceived Stress Scale

    mean and peak scores during follow-up

    Time frame: over 8-week follow up

  2. Penn Alcohol Craving Scale

    mean and peak score during follow up

    Time frame: over 8-week follow up

  3. Plasma cortisol

    Plasma cortisol measured in blood

    Time frame: Baseline/pre hydrocortisone and post-hydrocortisone

06

Study locations

1 of 1 sites recruiting
  • University of Pittsburgh
    Pittsburgh, Pennsylvania 15213, United States
    Recruiting
07

References and documents

Individual participant data

Plan to share: Yes — 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

Supporting information: Study protocol

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT07612631
Lead sponsor
Rajesh Narendran
Collaborators
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Responsible party
Rajesh Narendran (Professor of Radiology and Psychiatry, University of Pittsburgh) — Sponsor-investigator
First posted
May 29, 2026
Start date
Jun 1, 2026
Primary completion
Jun 30, 2031 (estimated)
Completion
Jun 30, 2032 (estimated)
Last update
Jun 3, 2026

Study contacts

Rajesh Narendran
Contact
narendranr@upmc.edu
412-647-5176
Rajesh Narendran
principal investigator · University of Pittsburgh

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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