- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05011760
[C-11]NPA PET-amphetamine in Cocaine Use Disorders
[C-11]NPA PET-amphetamine in Cocaine Use Disorders (Aim 2)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Rajesh Narendran, MD
- Phone Number: 4126475176
- Email: narendranr@upmc.edu
Study Locations
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15213
- Recruiting
- University of Pittsburgh
-
Contact:
- Rajesh Narendran
- Phone Number: 412-647-5176
- Email: narendranr@upmc.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Males or females between 18 and 55 years old
- Fulfil DSM-5 criteria for cocaine use disorder
- No other current DSM-5 psychiatric or addictive disorders (such as major depressive disorder, bipolar disorders, psychotic disorders, etc.,)
- 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);
- Not currently on prescription medical or psychotropic medications
- 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
- Not currently pregnant or breastfeeding
- No history of significant radioactivity exposure in past year from another research study or occupation that exceeds RDRC guidelines
- No metallic objects in the body that are contraindicated for MRI
- No baseline BP ≥ 140/90 and/or HR ≥ 100.
- No first-degree relative with an MI or stroke prior to middle age
- No first-degree relative with psychosis or mania.
- Completed a baseline [11C]NOP-1A PET scan in Aim 1 (Study Record: Imaging CRF X NOP interactions in Cocaine Use Disorders)
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)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PET
[C-11]NPA PET Scan
|
Radiotracer
Oral, 0.5 mg/Kg
Radiotracer
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
DELTA binding potential relative to non displaceable uptake (BPND)
Time Frame: Baseline, and 2.5 to 3 hours post-amphetamine
|
DELTA BPND is the change in BPND from the baseline PET scan to post-amphetamine PET scan that will be acquired 2.5 to 3 hours after d-amphetamine administration (0.5 mg/Kg, oral)
|
Baseline, and 2.5 to 3 hours post-amphetamine
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Rajesh Narendran, University of Pittsburgh
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Disease
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Dopamine Agents
- Dopamine Uptake Inhibitors
- Central Nervous System Stimulants
- Sympathomimetics
- Adrenergic Uptake Inhibitors
- Amphetamine
- Dextroamphetamine
Other Study ID Numbers
- STUDY20060171 (Aim 2)
- R01DA026472 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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