Imaging CRF X NOP Interactions in Alcohol Use Disorder

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.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Use Disorder
• Intervention / Treatment: Radiation: Baseline [C-11]NOP-1A PET scan; Drug: Hydrocortisone; Radiation: Post-hydrocortisone [C-11]NOP-1A PET scan

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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Rajesh Narendran; Phone Number: 412-647-5176; Email: narendranr@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PET; [C-11]NOP-1A	Radiation: Baseline [C-11]NOP-1A PET scan; Radiotracer; Drug: Hydrocortisone; Intravenous, 1 mg/Kg; Radiation: Post-hydrocortisone [C-11]NOP-1A PET scan; Radiotracer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perceived Stress Scale	mean and peak scores during follow-up	over 8-week follow up
Penn Alcohol Craving Scale	mean and peak score during follow up	over 8-week follow up
Plasma cortisol	Plasma cortisol measured in blood	Baseline/pre hydrocortisone and post-hydrocortisone

Collaborators and Investigators

• Sponsor: Rajesh Narendran
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Rajesh Narendran, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2026
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): June 30, 2032

Study Registration Dates

• First Submitted: May 16, 2026
• First Submitted That Met QC Criteria: May 22, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: [C-11]NOP-1A PET; Nociceptive opioid peptide receptor
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Alcoholism; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids; Hydrocortisone; BaseLine dental cement
• Other Study ID Numbers: STUDY25050039; R01AA032487 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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 Sharing Time Frame: Upon publication or study completion. Data will be available indefinitely on the data archives
• IPD Sharing Access Criteria: Available as per the NIAAA Data Archive repository criteria for access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No