Imaging CRF X NOP Interactions in Alcohol Use Disorder

NCT07612631 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: STUDY25050039R01AA032487
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Alcohol Use Disorder

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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

  Baseline/pre hydrocortisone, and 3-hours post hydrocortisone

• Total number of negative ETG tests

  Represents level of abstinence in contingency management

  over 8-week follow-up

Secondary Outcomes (5)

• Midbrain DELTA VT

  Baseline/pre hydrocortisone and 3-hours post hydrocortisone

• Ventral striatum DELTA VT

  Baseline/pre hydrocortisone and 3-hours post hydrocortisone

• Orbitofrontal Cortex DELTA VT

  Baseline/pre hydrocortisone and 3-hours post hydrocortisone

• Relapse to alcohol

  over 8-weeks follow up

• Relapse to alcohol severity (self-reported)

  over 8- week follow up

Other Outcomes (3)

• Perceived Stress Scale

  over 8-week follow up

• Penn Alcohol Craving Scale

  over 8-week follow up

• Plasma cortisol

  Baseline/pre hydrocortisone and post-hydrocortisone

Study Arms (1)

PET

EXPERIMENTAL

\[C-11\]NOP-1A

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

Interventions

Hydrocortisone DRUG

Intravenous, 1 mg/Kg

PET

Post-hydrocortisone [C-11]NOP-1A PET scan RADIATION

Radiotracer

PET

Baseline [C-11]NOP-1A PET scan RADIATION

Radiotracer

PET

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Rajesh Narendran: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Alcoholism

Interventions

BaseLine dental cement; Hydrocortisone

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Rajesh Narendran

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rajesh Narendran

CONTACT

412-647-5176; narendranr@upmc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Radiology and Psychiatry

Model Details: Alcohol use disorder and controls will receive the same intervention

Study Record Dates

• First Submitted: May 16, 2026
• First Posted: May 29, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): June 30, 2032
• Last Updated: June 3, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Upon publication or study completion. Data will be available indefinitely on the data archives
• Access Criteria: Available as per the NIAAA Data Archive repository criteria for access

Locations

US (1)