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

Not Applicable

Completed

• Conditions: Opiate Dependence; Cocaine Dependence
• Interventions: Diagnostic Test: 11UCB-J PET Scan

• Registration Number: NCT03527485
• Lead Sponsor: Yale University

Brief Summary

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.

Detailed Description

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.

A separate protocol from the study team, identified by the ClinicalTrials.gov ID NCT04721418, is conducting a comprehensive investigation into the cocaine use disorder group. Therefore, data for participants with cocaine use disorder are not included in the results for the current registration.

Study Timeline

• Study First Submitted: 2018-04-19
• Study First Submitted QC: 2018-05-16
• Study First Posted: 2018-05-17
• Study Start: 2019-01-01
• Primary Completion: 2023-03-28
• Study Completion: 2023-03-28
• Results First Submitted: 2024-02-23
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-24
• Last Update Submitted: 2024-06-24
• Results First Posted: 2024-07-16
• Last Update Posted: 2024-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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 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)).

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Healthy Controls (HC)	11UCB-J PET Scan	30 healthy controls; no substance dependence or mental health issues 11UCB-J PET Scan.
Opiate Use Disorder (OUD)	11UCB-J PET Scan	30 subjects meeting opiate dependence criteria will receive 11UCB-J PET Scan.

Primary Outcome Measures

Name	Time	Method
11C-UCB-J PET Synaptic Density	90 minute scan	PET scan- Participants underwent a single 11C-UCB-J PET scan to obtain measures of synaptic density (BPND). Structural magnetic resonance imaging (MRI) scans were also obtained for anatomical registration/partial volume correction (PVC) with the iterative Yang (IY) algorithm. BPND is a unitless metric. The study aimed to explore synaptic density differences in subjects with opioid use disorder compared to a control group within the sample.

Trial Locations

Locations (1)

CT Mental Health Center; 🇺🇸 New Haven, Connecticut, United States