Imaging CRF X NOP Interactions in CUD

NCT ID: NCT05008146

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-31
• Study Completion Date: 2028-09-01

Brief Summary

This study uses [11C]NOP-1A positron emission tomography (PET) and a hydrocortisone challenge to image the interaction between nociceptive opioid peptide (NOP) receptors and cortisol/corticotrophin releasing factor (CRF) in subjects with cocaine use disorders (CUD) and matched healthy controls (HC). It will also examine whether alterations in CRF x NOP interactions predict relapse in subjects with CUD.

Detailed Description

Cocaine use disorder (CUD) is a chronic disorder associated with numerous relapses and periods of abstinence.

Studies in CUD suggest that ~ 60 to 75% of abstinent addicts relapse over twelve months Documenting specific neurochemical abnormalities that lead to relapse in individuals with CUD has the potential to accelerate the development of medications to prevent relapse. Basic investigations postulate an imbalance between brain stress and anti-stress/resilience systems as the underlying mechanism that drives negative reinforcement, craving, and relapse in addiction. Nociceptin (N/OFQ), which binds to the nociceptive opioid peptide receptors (NOP) is a critical component of the brain's anti-stress system. N/OFQ counteracts the functional effects of the primary stress-promoting neuropeptide corticotrophin releasing factor (CRF) in the brain to exert its anti-stress effects. Studies have also shown that acute increases in CRF and stress are countered by increased NOP receptor expression (~ 10% ) in brain regions that regulate stress such as bed nucleus of the stria terminalis. PET studies with the NOP radiotracer [11C]NOP-1A show increased binding to NOP in CUD compared to HC. PET studies also show NOP receptors to upregulate (~ 15%) in response to an acute intravenous hydrocortisone challenge (1 mg/Kg). NOP upregulation may represent an adaptive mechanism in the brain to counteract stress-induced increases in cortisol and CRF. Here, we postulate a failure in this adaptive mechanism as a reason that leads to relapse in CUD. CUD subjects and HC will be studied with [11C]NOP-1A before and after an intravenous hydrocortisone challenge (aim 1). Hydrocortisone is used as a challenge because it increases cortisol and CRF in brain regions that regulate stress. We hypothesize that hydrocortisone-induced increases in [11C]NOP-1A binding (DELTA VT) will be smaller in CUD relative to HC, and this will be associated with less time to relapse in a 12-week follow up.

Conditions

Cocaine Use Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

PET

\[C-11\]NOP-1A

Group Type: EXPERIMENTAL

Baseline [C-11]NOP-1A PET Scan

Intervention Type: RADIATION

Radiotracer

Hydrocortisone

Intervention Type: DRUG

Intravenous, 1mg/Kg

Post-hydrocortisone [C-11]NOP-1A PET Scan

Intervention Type: RADIATION

Radiotracer

Interventions

Baseline [C-11]NOP-1A PET Scan

Radiotracer

Intervention Type: RADIATION

Hydrocortisone

Intravenous, 1mg/Kg

Intervention Type: DRUG

Post-hydrocortisone [C-11]NOP-1A PET Scan

Radiotracer

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

Cocaine use disorders (CUD)

1. Males or females between 18 and 55 years old

2. Fulfil DSM-5 criteria for cocaine use disorder

3. No other current DSM-5 psychiatric or addictive disorders (such as major depressive disorder, bipolar disorders, psychotic disorders, etc.,)

4. No current abuse (six months) of opiates, sedative-hypnotics, amphetamines, MDMA, etc., as well as moderate to severe alcohol or cannabis use (twice a week). Nicotine use will be quantified and controlled between groups using the Fagerstrom Test for Nicotine Dependence (Heatherton et al., 1991);

5. Not currently on prescription medical or psychotropic medications

6. No current or past severe medical, endocrine or neurological illnesses including glaucoma, seizure disorders, hypertension, hypercholesterolemia as assessed by a complete medical history and physical

7. Not currently pregnant or breastfeeding

8. No history of significant radioactivity exposure in past year from another research study or occupation that exceeds RDRC guidelines

9. No metallic objects in the body that are contraindicated for MRI

Healthy Controls (HC)

1. Males or females between 18 and 55 years old

2. No present or past DSM-5 disorders (other than nicotine dependence)

3. Criteria 5 to 9 as listed previously.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Rajesh Narendran

OTHER

Sponsor Role: lead

Responsible Party

Rajesh Narendran

Professor of Radiology and Psychiatry

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Rajesh Narendran, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Rajesh Narendran, MD

Role: CONTACT

narendranr@upmc.edu

4126475176

Facility Contacts

Rajesh Narendran

Role: primary

narendranr@upmc.edu

4126475176

Other Identifiers

R01DA026472

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY19110156

Identifier Type: OTHER

Identifier Source: secondary_id

STUDY20060171 (Aim 1)

Identifier Type: -

Identifier Source: org_study_id