[C-11]NPA PET-amphetamine in Cocaine Use Disorders

NCT ID: NCT05011760

Last Updated: 2025-06-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-31
• Study Completion Date: 2028-09-01

Brief Summary

This study uses [11C]NPA positron emission tomography (PET) and a d-amphetamine challenge to image amphetamine induced dopamine release in the striatum in subjects with cocaine use disorders (CUD). Amphetamine-induced dopamine release data from this study will be correlated with [11C]NOP-1A VT measured at baseline in the midbrain. [11C]NOP-1A PET data will be used from aim 1 (see, Study Record: Imaging CRF X NOP interactions in Cocaine Use Disorders)

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 exerts its anti-stress effect by counteracting the functional effects of the primary stress-promoting neuropeptide corticotrophin releasing factor (CRF) in the brain. 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. Mechanistic studies have also shown N/OFQ to act on ventral tegmental area/midbrain NOP receptors to inhibit the firing of dopamine neurons and limit reward to cocaine. Imaging amphetamine-induced dopamine release in a subset of CUD subjects who participate in aim 1 will allow us to link midbrain NOP receptor expression with ventral striatum (VST) dopamine release and examine its role in reinforcement (aim 2). The aims proposed in this study have the potential to clarify the role of N/OFQ and NOP in stress, reward, and relapse in CUD.

Conditions

Cocaine Use Disorder

Study Design

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

Study Groups

PET

\[C-11\]NPA PET Scan

Group Type: EXPERIMENTAL

Baseline [C-11]NPA PET Scan

Intervention Type: RADIATION

Radiotracer

d-amphetamine

Intervention Type: DRUG

Oral, 0.5 mg/Kg

Post-amphetamine [C-11]NPA PET Scan

Intervention Type: RADIATION

Radiotracer

Interventions

Baseline [C-11]NPA PET Scan

Radiotracer

Intervention Type: RADIATION

d-amphetamine

Oral, 0.5 mg/Kg

Intervention Type: DRUG

Post-amphetamine [C-11]NPA PET Scan

Radiotracer

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

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, and MDMA 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

10. No baseline BP ≥ 140/90 and/or HR ≥ 100.

11. No first-degree relative with an MI or stroke prior to middle age

12. No first-degree relative with psychosis or mania.

13. Completed a baseline [11C]NOP-1A PET scan in Aim 1 (Study Record: Imaging CRF X NOP interactions in Cocaine Use Disorders)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

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

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

412-647-5176

Other Identifiers

R01DA026472

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY20060171 (Aim 2)

Identifier Type: -

Identifier Source: org_study_id