Trial Outcomes & Findings for Investigation of Cocaine Addiction Using mGluR5 PET and fMRI (NCT NCT03471182)

Last Updated: 2024-02-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

32 participants

Primary outcome timeframe

Following 2-5 days of cocaine abstinence

Results posted on

2024-02-29

Participant Flow

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.

Of 32 enrolled individuals, 17 met inclusion criteria for participants with cocaine-use disorder and 8 met criteria as healthy-comparison participants. Twenty historical healthy-comparison participants were not considered enrolled in this study.

Participant milestones

Participant milestones
Measure	Adults With a Cocaine-use Disorder (CUD) Non-treatment-seeking, medically healthy adults meeting DSM-5 criteria for a moderate or severe cocaine-use disorder.	Healthy Comparison Adults, MRI (HC-MRI) Medically and psychologically healthy adults enrolled in this study to complete the magnetic resonance imaging (MRI) procedures as part of a comparison Group to examine MRI Outcome Measures.	Historical Healthy Comparison Adults, PET (HHC-PET) A historical sample of medically and psychologically healthy adults completing positron emission tomography (PET) procedures. This sample was compiled uniquely for this study from a larger set of historical data to form a comparison Group to examine PET Outcome Measures.
Overall Study STARTED	17	8	20
Overall Study Completed MRI Procedures	16	7	0
Overall Study Completed PET Procedures	15	0	0
Overall Study Completing Both MRI and PET	14	0	0
Overall Study COMPLETED	14	7	20
Overall Study NOT COMPLETED	3	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Adults With a Cocaine-use Disorder (CUD) Non-treatment-seeking, medically healthy adults meeting DSM-5 criteria for a moderate or severe cocaine-use disorder.	Healthy Comparison Adults, MRI (HC-MRI) Medically and psychologically healthy adults enrolled in this study to complete the magnetic resonance imaging (MRI) procedures as part of a comparison Group to examine MRI Outcome Measures.	Historical Healthy Comparison Adults, PET (HHC-PET) A historical sample of medically and psychologically healthy adults completing positron emission tomography (PET) procedures. This sample was compiled uniquely for this study from a larger set of historical data to form a comparison Group to examine PET Outcome Measures.
Overall Study Withdrawal by Subject	1	1	0
Overall Study Technical failure	2	0	0

Baseline Characteristics

Investigation of Cocaine Addiction Using mGluR5 PET and fMRI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adults With a Cocaine-use Disorder (CUD) n=17 Participants Non-treatment-seeking, medically healthy adults meeting DSM-5 criteria for a moderate or severe cocaine-use disorder.	Healthy Comparison Adults, MRI (HC-MRI) n=8 Participants Medically and psychologically healthy adults enrolled in this study to complete the magnetic resonance imaging (MRI) procedures as part of a comparison Group to examine MRI Outcome Measures.	Historical Healthy Comparison Adults, PET (HHC-PET) n=20 Participants A historical sample of medically and psychologically healthy adults completing positron emission tomography (PET) procedures. This sample was compiled uniquely for this study from a larger set of historical data to form a comparison Group to examine PET Outcome Measures.	Total n=45 Participants Total of all reporting groups
Age, Continuous	49.3 years STANDARD_DEVIATION 6.5 • n=5 Participants	36.6 years STANDARD_DEVIATION 4.8 • n=7 Participants	49.0 years STANDARD_DEVIATION 7.4 • n=5 Participants	46.5 years STANDARD_DEVIATION 8.2 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants	13 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants	32 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	8 Participants n=7 Participants	19 Participants n=5 Participants	42 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants	17 Participants n=4 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants	26 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	17 participants n=5 Participants	8 participants n=7 Participants	20 participants n=5 Participants	45 participants n=4 Participants
Positive toxicology screen indicating recent cocaine use	17 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	17 Participants n=4 Participants

PRIMARY outcome

Timeframe: Following 2-5 days of cocaine abstinence

Population: Standard analysis of PET data requires a high-resolution MRI image for anatomical localization; thus only participants with a CUD completing both PET and MRI procedures(N=14 CUD) were analyzed. PET data was not collected on the Group healthy comparison adults completing only MRI procedures (HC-MRI).

Outcome measures

Outcome measures
Measure	Adults With a Cocaine-use Disorder (CUD) n=14 Participants Non-treatment-seeking, medically healthy adults meeting DSM-5 criteria for a moderate or severe cocaine-use disorder.	Historical Healthy Comparison Adults, PET (HHC-PET) n=20 Participants A historical sample of medically and psychologically healthy adults completing positron emission tomography (PET) procedures. This sample was compiled uniquely for this study from a larger set of historical data to form a comparison Group to examine PET Outcome Measures.
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Ventral striatum	36.48 mL*cm^3 Standard Deviation 8.05	32.19 mL*cm^3 Standard Deviation 5.58
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Caudate	25.67 mL*cm^3 Standard Deviation 7.29	22.41 mL*cm^3 Standard Deviation 4.75
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Putamen	30.31 mL*cm^3 Standard Deviation 5.84	26.06 mL*cm^3 Standard Deviation 5.26
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Orbitofrontal cortex	30.40 mL*cm^3 Standard Deviation 6.13	26.36 mL*cm^3 Standard Deviation 4.61
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Anterior cingulate cortex	32.54 mL*cm^3 Standard Deviation 6.88	28.73 mL*cm^3 Standard Deviation 5.54
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Ventromedial prefrontal cortex	33.95 mL*cm^3 Standard Deviation 7.21	29.41 mL*cm^3 Standard Deviation 5.34
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Inferior frontal gyrus	28.42 mL*cm^3 Standard Deviation 6.08	24.78 mL*cm^3 Standard Deviation 4.25
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Middle frontal gyrus	28.37 mL*cm^3 Standard Deviation 6.94	24.95 mL*cm^3 Standard Deviation 4.36
Regional Availability of Metabotropic Glutamate Type-5 Receptors (mGluR5) Superior frontal gyrus	27.55 mL*cm^3 Standard Deviation 6.33	23.65 mL*cm^3 Standard Deviation 4.30

PRIMARY outcome

Timeframe: Following 2-5 days of cocaine abstinence.

Population: All participants who performed a Go/NoGo task during MRI procedures. Functional MRI data of Go/NoGo performance was not collected on the Group historical healthy comparison adults who had completed PET procedures (HHC-PET).

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).

Outcome measures

Outcome measures
Measure	Adults With a Cocaine-use Disorder (CUD) n=16 Participants Non-treatment-seeking, medically healthy adults meeting DSM-5 criteria for a moderate or severe cocaine-use disorder.	Historical Healthy Comparison Adults, PET (HHC-PET) n=7 Participants A historical sample of medically and psychologically healthy adults completing positron emission tomography (PET) procedures. This sample was compiled uniquely for this study from a larger set of historical data to form a comparison Group to examine PET Outcome Measures.
Functional Brain Network Engagement Associated With Response Inhibition Right frontoparietal network	0.409 Unitless beta coefficient Standard Error 0.103	0.125 Unitless beta coefficient Standard Error 0.156
Functional Brain Network Engagement Associated With Response Inhibition Left frontoparietal network	0.349 Unitless beta coefficient Standard Error 0.159	0.037 Unitless beta coefficient Standard Error 0.241
Functional Brain Network Engagement Associated With Response Inhibition Basal ganglia network	0.175 Unitless beta coefficient Standard Error 0.103	-0.240 Unitless beta coefficient Standard Error 0.156
Functional Brain Network Engagement Associated With Response Inhibition Cingulo-insula network	0.103 Unitless beta coefficient Standard Error 0.121	-0.271 Unitless beta coefficient Standard Error 0.183

PRIMARY outcome

Timeframe: Following 2-5 days of cocaine abstinence.

Population: Participants who completed resting-state functional MRI procedures. Two the 16 CUD participants completing MRI were excluded from analysis due to insufficient data and poor image quality resulting from excessive head motion. Resting-state functional MRI data were not available on the Group historical healthy comparison adults who had completed PET procedures (HHC-PET).

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.

Outcome measures

Outcome measures
Measure	Adults With a Cocaine-use Disorder (CUD) n=14 Participants Non-treatment-seeking, medically healthy adults meeting DSM-5 criteria for a moderate or severe cocaine-use disorder.	Historical Healthy Comparison Adults, PET (HHC-PET) n=7 Participants A historical sample of medically and psychologically healthy adults completing positron emission tomography (PET) procedures. This sample was compiled uniquely for this study from a larger set of historical data to form a comparison Group to examine PET Outcome Measures.
Resting-state Functional Brain Network Activity, Fractional Amplitude of Low-frequency Fluctuations (fALFF) Cingulo-insula network	0.707 Unitless ratio Standard Error 0.029	0.726 Unitless ratio Standard Error 0.041
Resting-state Functional Brain Network Activity, Fractional Amplitude of Low-frequency Fluctuations (fALFF) Default-mode network	0.747 Unitless ratio Standard Error 0.021	0.726 Unitless ratio Standard Error 0.030
Resting-state Functional Brain Network Activity, Fractional Amplitude of Low-frequency Fluctuations (fALFF) Right frontoparietal network	0.749 Unitless ratio Standard Error 0.019	0.772 Unitless ratio Standard Error 0.026
Resting-state Functional Brain Network Activity, Fractional Amplitude of Low-frequency Fluctuations (fALFF) Left frontoparietal network	0.739 Unitless ratio Standard Error 0.021	0.734 Unitless ratio Standard Error 0.030
Resting-state Functional Brain Network Activity, Fractional Amplitude of Low-frequency Fluctuations (fALFF) Basal ganglia network	0.636 Unitless ratio Standard Error 0.036	0.590 Unitless ratio Standard Error 0.051

Adverse Events

Adults With a Cocaine-use Disorder (CUD)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Comparison Adults, MRI (HC-MRI)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Patrick Worhunsky

Yale University School of Medicine

Phone: 203-737-2668

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place