Cocaine Dependence, Opiate Dependence
Conditions
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.
Interventions
DIAGNOSTIC_TEST11UCB-J PET Scan
11UCB-J PET Scan
Sponsors
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
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)).
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Opiate Use Disorder (OUD) 15 subjects meeting opiate dependence criteria will receive 11UCB-J PET Scan.
11UCB-J PET Scan: 11UCB-J PET Scan | 15 |
| Healthy Controls (HC) 26 healthy controls; no substance dependence or mental health issues 11UCB-J PET Scan.
11UCB-J PET Scan: 11UCB-J PET Scan | 26 |
| Total | 41 |
Baseline characteristics
| Characteristic | Opiate Use Disorder (OUD) | Healthy Controls (HC) | Total |
|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 6.5 | 36.7 years STANDARD_DEVIATION 10.6 | 37.0 years STANDARD_DEVIATION 9.2 |
| Race/Ethnicity, Customized African American/Black (Non-Hispanic) | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other or Unknown | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White (Non-Hispanic) | 15 Participants | 22 Participants | 37 Participants |
| Region of Enrollment United States | 15 participants | 26 participants | 41 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 12 Participants |
| Sex: Female, Male Male | 10 Participants | 19 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 26 |
| other Total, other adverse events | 0 / 15 | 0 / 26 |
| serious Total, serious adverse events | 0 / 15 | 0 / 26 |
Outcome results
Primary
11C-UCB-J PET Synaptic Density
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.
Time frame: 90 minute scan
Population: All participants who underwent 11C-UCB-J PET and MRI scans
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Opiate Use Disorder (OUD) | 11C-UCB-J PET Synaptic Density | Region of Interest: Ventral Striatum (VS) | 4.01 unitless | Standard Deviation 0.7 |
| Opiate Use Disorder (OUD) | 11C-UCB-J PET Synaptic Density | Region of Interest: Prefrontal Cortex (PFC) | 4.62 unitless | Standard Deviation 0.87 |
| Healthy Controls (HC) | 11C-UCB-J PET Synaptic Density | Region of Interest: Ventral Striatum (VS) | 4.52 unitless | Standard Deviation 0.53 |
| Healthy Controls (HC) | 11C-UCB-J PET Synaptic Density | Region of Interest: Prefrontal Cortex (PFC) | 5.09 unitless | Standard Deviation 0.61 |
p-value: 0.011ANOVA
p-value: 0.044ANOVA