Imaging CRF X NOP Interactions in CUD

Early Phase 1

Recruiting

• Conditions: Cocaine Use Disorder
• Interventions: Radiation: Baseline [C-11]NOP-1A PET Scan; Drug: Hydrocortisone; Radiation: Post-hydrocortisone [C-11]NOP-1A PET Scan

• Registration Number: NCT05008146
• Lead Sponsor: Rajesh Narendran

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.

Study Timeline

• Study Start: 2020-12-31
• Study First Submitted: 2021-08-11
• Study First Submitted QC: 2021-08-13
• Study First Posted: 2021-08-17
• Status Verified: 2024-05
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-13
• Primary Completion: 2028-09-01
• Study Completion: 2028-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PET	Baseline [C-11]NOP-1A PET Scan	\[C-11\]NOP-1A
PET	Post-hydrocortisone [C-11]NOP-1A PET Scan	\[C-11\]NOP-1A
PET	Hydrocortisone	\[C-11\]NOP-1A

Primary Outcome Measures

Name	Time	Method
DELTA VT	Baseline, and 3 hours post-hydrocortisone	VT is the volumes of distribution expressed relative to total plasma ligand concentration; Delta VT is the change in VT from baseline to 3-hours post-hydrocortisone.

Trial Locations

Locations (1)

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States