A Phase 1 interventional study of Psychiatric and Cognitive Testing and Cocaine Self-adminstration in Cocaine Dependence, sponsored by Yale University. Completed at 1 site in United States. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-02-29.
Sponsored by Yale University · Phase 1, Interventional, and Other
The proposed research program will investigate the changes in brain chemistry and circuitry that 're-wire' the brain during chronic cocaine use, promote relapse, and complicate treatment efforts. Currently-using and non-treatment-seeking individuals with a cocaine use disorder will undergo a cocaine self-administration paradigm 2-5 days prior to completing positron emission tomography (PET) and functional magnetic resonance imaging (fMRI).
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.
416 studies on the registry are indexed under Cocaine-Related Disorders; 12 are open to participants now.
This study's enrollment of 32 is below the median of 60 across 313 interventional studies indexed under Cocaine-Related Disorders.
Browse Cocaine-Related Disorders studies →Yale University is the lead sponsor of 1,770 studies on the registry; 294 are open to participants now.
Of its 221 completed or terminated interventional studies of FDA-regulated products, 129 (58%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
All participants:
Participants with a cocaine use disorder:
Healthy comparison participants:
Exclusion Criteria:
All participants:
Participants with a cocaine use disorder:
Healthy comparison participants:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All participants will complete psychiatric assessment and cognitive testing.
Behavioral: Psychiatric and Cognitive Testing
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
All participants will complete a PET scan to assess mGluR5 receptors using \[18-F\]FPEB
Radiation: Positron Emission Tomography
All participants will complete one MRI scan to assess brain structure and function.
Other: Magnetic Resonance Imaging
Interviews, questionnaires, and computer testing.
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.
Also known as: cocaine hydrochloride
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.
Also known as: PET
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.
Also known as: MRI, functional MRI
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5)
Receptor availability assessed as the volume of distribution (VT) of \[18F\]FPEB radiotracer, measured using positron emission tomography (PET). Higher \[18F\]FPEB VT values indicate a greater availability of mGluR5 receptors.
Time frame: Following 2-5 days of cocaine abstinence
Functional Brain Network Engagement Associated With Response Inhibition
Independent component analysis (ICA) of functional MRI data separates brain activity associated with distinct functional networks. Comparing the activity in these networks to the fMRI task events using a regression analysis produces a beta-weight where a larger beta indicates the network was more activated or 'engaged' in processing the task demands. In this study, participants completed a Go/NoGo task to assess brain processing associated with infrequent-stimulus response inhibition (i.e., correct NoGo's) compared to frequent-stimulus responses (i.e., correct Go's).
Time frame: Following 2-5 days of cocaine abstinence.
Resting-state Functional Brain Network Activity, Fractional Amplitude of Low-frequency Fluctuations (fALFF)
Independent component analysis (ICA) of functional MRI data separates brain activity associated with distinct functional networks. The fractional amplitude of low-frequency fluctuations (fALFF) during resting-state reflects a measure of the general health status of a network, comprised of both the strength of network activity and within-network connectivity absent of any specific cognitive demands.
Time frame: Following 2-5 days of cocaine abstinence.
Participants were recruited from the New Haven, CT community, through current/past enrollment in similar research at the Cocaine Research Clinic and Yale PET Center as well as through community advertising (e.g., flyers). The first participant was enrolled on February 26, 2018 and the last participant was enrolled on June 30, 2022.
| Milestone | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) | Historical Healthy Comparison Adults, PET (HHC-PET) |
|---|---|---|---|
| Started | 17 | 8 | 20 |
| Completed mri procedures | 16 | 7 | 0 |
| Completed pet procedures | 15 | 0 | 0 |
| Completing both mri and pet | 14 | 0 | 0 |
| Completed | 14 | 7 | 20 |
| Not completed | 3 | 1 | 0 |
| Withdrew: Withdrawal by subject | 1 | 1 | 0 |
| Withdrew: Technical failure | 2 | 0 | 0 |
Receptor availability assessed as the volume of distribution (VT) of \[18F\]FPEB radiotracer, measured using positron emission tomography (PET). Higher \[18F\]FPEB VT values indicate a greater availability of mGluR5 receptors.
| mL*cm^3 | Adults With a Cocaine-use Disorder (CUD) | Historical Healthy Comparison Adults, PET (HHC-PET) |
|---|---|---|
| Ventral striatum | 36.48 ± 8.05 | 32.19 ± 5.58 |
| Caudate | 25.67 ± 7.29 | 22.41 ± 4.75 |
| Putamen | 30.31 ± 5.84 | 26.06 ± 5.26 |
| Orbitofrontal cortex | 30.40 ± 6.13 | 26.36 ± 4.61 |
| Anterior cingulate cortex | 32.54 ± 6.88 | 28.73 ± 5.54 |
| Ventromedial prefrontal cortex | 33.95 ± 7.21 | 29.41 ± 5.34 |
| Inferior frontal gyrus | 28.42 ± 6.08 | 24.78 ± 4.25 |
| Middle frontal gyrus | 28.37 ± 6.94 | 24.95 ± 4.36 |
| Superior frontal gyrus | 27.55 ± 6.33 | 23.65 ± 4.30 |
Independent component analysis (ICA) of functional MRI data separates brain activity associated with distinct functional networks. Comparing the activity in these networks to the fMRI task events using a regression analysis produces a beta-weight where a larger beta indicates the network was more activated or 'engaged' in processing the task demands. In this study, participants completed a Go/NoGo task to assess brain processing associated with infrequent-stimulus response inhibition (i.e., correct NoGo's) compared to frequent-stimulus responses (i.e., correct Go's).
| Unitless beta coefficient | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) |
|---|---|---|
| Right frontoparietal network | 0.409 ± 0.103 | 0.125 ± 0.156 |
| Left frontoparietal network | 0.349 ± 0.159 | 0.037 ± 0.241 |
| Basal ganglia network | 0.175 ± 0.103 | -0.240 ± 0.156 |
| Cingulo-insula network | 0.103 ± 0.121 | -0.271 ± 0.183 |
Independent component analysis (ICA) of functional MRI data separates brain activity associated with distinct functional networks. The fractional amplitude of low-frequency fluctuations (fALFF) during resting-state reflects a measure of the general health status of a network, comprised of both the strength of network activity and within-network connectivity absent of any specific cognitive demands.
| Unitless ratio | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) |
|---|---|---|
| Default-mode network | 0.747 ± 0.021 | 0.726 ± 0.030 |
| Right frontoparietal network | 0.749 ± 0.019 | 0.772 ± 0.026 |
| Left frontoparietal network | 0.739 ± 0.021 | 0.734 ± 0.030 |
| Basal ganglia network | 0.636 ± 0.036 | 0.590 ± 0.051 |
| Cingulo-insula network | 0.707 ± 0.029 | 0.726 ± 0.041 |
Collected over Less than 30 days, typically 1-2weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Adults With a Cocaine-use Disorder (CUD) | 0/17 (0%) | 0/17 (0%) | 0/17 (0%) |
| Healthy Comparison Adults, MRI (HC-MRI) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) |
In addition to participants enrolled in this study (N=17 CUD, N=8 HC-MRI), baseline characteristics are provided for the sample of comparison adults completing PET procedures (N=20 HC-PET) as part of other studies.
| Age, Continuous(years) | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) | Historical Healthy Comparison Adults, PET (HHC-PET) | Total |
|---|---|---|---|---|
| Mean | 49.3 ± 6.5 | 36.6 ± 4.8 | 49.0 ± 7.4 | 46.5 ± 8.2 |
| Sex: Female, Male(Participants) | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) | Historical Healthy Comparison Adults, PET (HHC-PET) | Total |
|---|---|---|---|---|
| Female | 5 | 1 | 7 | 13 |
| Male | 12 | 7 | 13 | 32 |
| Ethnicity (NIH/OMB)(Participants) | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) | Historical Healthy Comparison Adults, PET (HHC-PET) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 2 | 0 | 1 | 3 |
| Not Hispanic or Latino | 15 | 8 | 19 | 42 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) | Historical Healthy Comparison Adults, PET (HHC-PET) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 2 | 0 | 2 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 8 | 1 | 8 | 17 |
| White | 9 | 5 | 12 | 26 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) | Historical Healthy Comparison Adults, PET (HHC-PET) | Total |
|---|---|---|---|---|
| United States | 17 | 8 | 20 | 45 |
| Positive toxicology screen indicating recent cocaine use(Participants) | Adults With a Cocaine-use Disorder (CUD) | Healthy Comparison Adults, MRI (HC-MRI) | Historical Healthy Comparison Adults, PET (HHC-PET) | Total |
|---|---|---|---|---|
| Count of participants | 17 | 0 | 0 | 17 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Consistent with NIH Grants Policy on Sharing of Unique Research Resources, including the "Sharing of Biomedical Research Resources: Principles and Guidelines for Recipients of NIH Grants and Contracts" (December, 1999), all research resources generated will be freely distributed, as available, to appropriate, qualified academic investigators for non-commercial research purposes. All data will be de-identified before sharing, using procedures in compliance with HIPPA and Yale Human Investigation Committee standards. No available data sets or supporting information will contain subject names, addresses or other specific personal identification.
Supporting information: Study protocol, Statistical analysis plan, Clinical study report, Analytic code
Time frame: In accordance with institutional standards and guidelines, after termination of this study and completion of all analysis and publications, all data and screening information will be anonymized and kept in a secure fashion for the purpose of further analyses indefinitely unless prevailing University or Federal guidelines at the time require a change.
Access criteria: In accordance with institutional standards and guidelines, researchers must submit a requisition form that describes their specific hypotheses and details specific data or supporting information being requested. Requests will be reviewed by senior study personnel.
Ran from Feb 2018 to primary completion in Aug 2022, 53 months.
Results were first posted in Oct 2023, 1 year 1 month after primary completion.
Of 14 phase 1 interventional studies under Cocaine-Related Disorders, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 14 and three quarters within 53. This study's 53 months is above that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Cocaine