Investigation of Cocaine Addiction Using mGluR5 PET and fMRI
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|ClinicalTrials.gov Identifier: NCT03471182|
Recruitment Status : Recruiting
First Posted : March 20, 2018
Last Update Posted : March 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Cocaine Dependence||Behavioral: Psychiatric and Cognitive Testing Drug: Cocaine Self-adminstration Radiation: Positron Emission Tomography Other: Magnetic Resonance Imaging||Phase 1|
Cocaine use disorder (CUD) remains a significant public health concern that is resistant to current treatments. Challenges to treating CUD include an imbalance in neurobiological systems that 're-wire' the brain such that appetitive and habitual processes influence decision-making and behavior. This research project aims to provide insight into this reorganized circuitry in CUD by investigating neurofunctional systems related to glutamatergic plasticity and functional brain networks during initial (2-5 days) abstinence. To target this potentially critical period of recovery, currently-using and non-treatment-seeking individuals with CUD will undergo a cocaine self-administration paradigm 2-5 days prior to completing [18F]FPEB positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Healthy comparison (HC) subjects that have participated in [18F]FPEB PET as part of other Yale approved protocols will be recruited to participate in the fMRI portion of this study.
Aim 1: To determine the availability of mGluR5 using [18F]FPEB PET during initial abstinence in individuals with CUD. The investigators hypothesize individuals with CUD, relative to HC, will exhibit concurrently and regionally specific increases (e.g., in the striatum) and decreases (e.g., in the prefrontal cortex) in mGluR5 availability.
Aim 2: To determine patterns of resting-state, response-inhibition, an automaticity related connectivity within and between large-scale functional networks using fMRI during initial abstinence in individuals with CUD. The investigators hypothesize network-based analyses of fMRI will reveal lower frontoparietal and greater limbic network modulation in CUD as compared to HC.
Aim 3: To explore the relationships between mGluR5 availability and functional network activity during initial abstinence in individuals with CUD. The investigators will perform multi-modal analysis of PET and fMRI data to examine links between molecular and functional systems in CUD using emerging 'fusion' approaches. While exploratory in nature, the investigators expect to find links between alterations in mGluR5 systems and functional reorganization in CUD (e.g., greater dorsostriatal mGluR5 may be linked to blunted frontoparietal inhibition).
Aim 4: To explore the relationships between mGluR5 availability, functional network activity (and their linkages) with cocaine self-administration, disease severity and chronicity, and psychometric assessments of impulsivity and compulsivity. While exploratory in nature, the investigators expect more substantial neurofunctional alterations during initial abstinence will be associated with greater cocaine self-administration, disease severity, impulsivity and compulsivity in individuals with CUD.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Investigation of Cocaine Addiction Using mGluR5 PET and fMRI|
|Actual Study Start Date :||February 26, 2018|
|Estimated Primary Completion Date :||June 2022|
|Estimated Study Completion Date :||June 2022|
Active Comparator: Psychiatric and Cognitive Testing
All participants will complete psychiatric assessment and cognitive testing.
Behavioral: Psychiatric and Cognitive Testing
Interviews, questionnaires, and computer testing.
Active Comparator: Cocaine Self-adminstration
This arm plans to assess the subjective (e.g., euphoric) and behavioral effects (e.g., self-administration) of cocaine in experienced, non-treatment seeking users of the drug in a human laboratory study of self-regulated cocaine administration.
Drug: Cocaine Self-adminstration
The intervention will include a training and safety session that consists of physician/nurse-administered cocaine followed by a self-regulated cocaine administration period under carefully controlled and closely monitored conditions.
Other Name: cocaine hydrochloride
Active Comparator: Positron Emission Tomography
All participants will complete a PET scan to assess mGluR5 receptors using [18-F]FPEB
Radiation: Positron Emission Tomography
PET scans will be performed on a High Resolution Research Tomograph (HRRT), the highest resolution human brain scanner available. Antecubital venous catheters will be used for IV administration of the radiotracer and for venous blood sampling. A radial artery catheter may also be inserted by an experienced physician before the PET scan. At the beginning of each scan, the participants's head will be immobilized and a 6-minute transmission scan, using an orbiting 137Cs point-source, is obtained and used for attenuation correction. PET scans will be acquired using bolus or bolus plus constant infusion administration of [18F]FPEB.
Other Name: PET
Active Comparator: Magnetic Resonance Imaging
All participants will complete one MRI scan to assess brain structure and function.
Other: Magnetic Resonance Imaging
Structural and functional MRI data will be acquired using a Siemens Trio TIM 3.0T system at the Yale Magnetic Resonance Research Center. High-resolution structural MRI data will be acquired to facilitate analysis of PET data and may be used in additional analysis of tissue volume and brain structure. Resting-state and task-based functional MRI data will be acquired using state-of-the-art multiband echo-planar imaging (EPI) gradient-echo sequences. Diffusion-weighted MRI data will also be acquired using multiband imaging sequences to investigate anatomical connectivity.
Other Name: MRI, functional MRI
- Glutamate receptor (mGluR5) availability [ Time Frame: Within 2-5 days of self-administration in cocaine participants; within 5 days of fMRI as possible for healthy comparison participants ]Glutamate receptor (mGluR5) availability as measured during [18F]FPEB PET
- Brain activity patterns [ Time Frame: Within 2-5 days of self-administration in cocaine participants; within 5 days of PET as possible for healthy comparison participants ]Brain activity patterns as measured during task-based and resting-state fMRI
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03471182
|Contact: Jessica Costeines, MAemail@example.com|
|United States, Connecticut|
|Connecticut Mental Health Center||Recruiting|
|New Haven, Connecticut, United States, 06519|
|Contact: Jessica Costeines 203-974-7559 firstname.lastname@example.org|
|Principal Investigator: Patrick Worhunsky, PhD|
|Principal Investigator:||Patrick Worhunsky, PhD||Assistant Professor|