Imaging Synaptic Density in Cocaine and Opiate Addiction In Vivo Using 11UCB-J PET

This study aims to measure synaptic density in the brains (including in ventral striatum [VS] and medial prefrontal cortex [mPFC]) of abstinent subjects with Cocaine Use Disorder (CUD) or Opiate Use Disorder (OUD) as compared to healthy control (HC) subjects using 11C-UCB-J PET. Subjects will undergo a single 11C-UCB-J (also known as 11C-APP311) PET scan.

This would be the very first to image synaptic density in human cocaine and opiate users, thereby testing whether altered synaptic density in the rodent brain is recapitulated in CUD and OUD humans. If confirmed, the current study would provide compelling clinical-translational support for an important pathophysiological mechanism of addiction - aberrant structural synaptic plasticity. As such, the current study has considerable potential for advancing the neurobiological understanding of human cocaine and opiate addiction.

Study Overview

• Status: Completed
• Conditions: Cocaine Dependence; Opiate Dependence
• Intervention / Treatment: Diagnostic test: 11UCB-J PET Scan

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marcella Mignosa, MD; Phone Number: (203) 974-7253; Email: marcella.mignosa@yale.edu

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • CT Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 21-55 years;
• Voluntary, written, informed consent;
• Physically healthy by medical history, physical, neurological, ECG and laboratory examinations;
• DSM-5 criteria for Cocaine Use Disorder or Opiate Use Disorder;
• Documented evidence (by urine toxicology) of 2 weeks abstinence from cocaine and 4 weeks abstinence from opiates;
• For females, a negative serum pregnancy (HCG) test;
• Full scale and verbal IQs > 80 (Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV)).

Exclusion Criteria:

• A history of other substance dependence (e.g., alcohol, sedative hypnotics), except for nicotine;
• A primary DSM-5 Axis I major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) as determined by the Structured Clinical Interview for DSM-5 (SCID-5);
• A history of significant and uncontrolled medical (e.g., cardiovascular, diabetic/metabolic) or neurological (e.g., cerebrovascular, seizures, traumatic brain injury) illness;
• A history of seizures;
• Current use of psychotropic and/or potentially psychoactive prescription medications;
• Medical contraindications to participation in a magnetic resonance (MR) imaging procedure (e.g., ferromagnetic implants/foreign bodies, claustrophobia, cardiac pacemaker, prosthetic valve, otologic implant, etc.) as recorded on the MR safety sheet;
• For females, physical or laboratory (HCG) evidence of pregnancy;
• PTT and PT/INR lab results not appropriate for arterial line placement;
• Taking anticoagulants;
• Being prescribed methadone/buprenorphine upon screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Opiate Use Disorder (OUD); 30 subjects meeting opiate dependence criteria will receive 11UCB-J PET Scan.	Diagnostic test: 11UCB-J PET Scan; 11UCB-J PET Scan
Other: Cocaine Use Disorder (CUD); 30 subjects meeting cocaine dependence criteria 11UCB-J PET Scan.	Diagnostic test: 11UCB-J PET Scan; 11UCB-J PET Scan
Other: Healthy Controls (HC); 30 healthy controls; no substance dependence or mental health issues 11UCB-J PET Scan.	Diagnostic test: 11UCB-J PET Scan; 11UCB-J PET Scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
11C-UCB-J PET synaptic density	PET scan	90 minute scan

Collaborators and Investigators

• Sponsor: Yale University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2019
• Primary Completion (Actual): March 28, 2023
• Study Completion (Actual): March 28, 2023

Study Registration Dates

• First Submitted: April 19, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 17, 2018

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Cocaine-Related Disorders
• Other Study ID Numbers: 2000021843

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No