Longitudinal Assessment of Functional Connectivity in Treatment Engaged Cocaine Users

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ClinicalTrials.gov Identifier: NCT03554928

Recruitment Status : Completed

First Posted : June 13, 2018

Last Update Posted : July 23, 2019

Sponsor:

Information provided by (Responsible Party):

Colleen A Hanlon, PhD, Medical University of South Carolina

Study Description

Brief Summary:

High-relapse rates to addiction are likely due to motivational (limbic) and cognitive (executive) factors. The purpose of this proposal is to determine the relationship between functional connectivity in executive control regions (namely the dorsolateral prefrontal cortex) and both proximal and extended outcomes in treatment seeking cocaine and opiate users. This longitudinal neuroimaging study will assess the integrity of executive and limbic circuits 4 timepoints before and after a 28-day intensive outpatient treatment program. Controls will also be recruited as a comparison group. The fundamental neuroscience knowledge gained from this proposal will be used to develop new evidence-based brain stimulation treatment strategies to enhance the integrity of these circuits and subsequent outcomes in traditional treatment programs.

The purpose of this study is not only to look at the integrity of these circuits in individuals entering treatment but also to see how these circuits change after treatment and if this can be used to predict outcomes. From the larger societal perspective this research may help us determine which individuals are likely going to benefit the most from treatment and perhaps those that are at a greater risk for relapse.

Condition or disease	Intervention/treatment
Cocaine Dependence Substance Use Disorders	Diagnostic Test: magnetic resonance imaging

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Detailed Description:

Chronic cocaine use is among the most difficult substance-use disorders to treat. High relapse rates are likely due to a combination of factors that involve limbic and executive circuits in the brain, including vulnerability to salient cues and loss of cognitive control . This may be due to elevated functional activity within limbic neural circuitry, in the presence of a salient cue or to attenuated activity in executive control circuitry, which is impaired in users and is likely required to resist the limbic drive to use cocaine among individuals trying to remain abstinent.

Although predicting cocaine relapse after traditional outpatient treatment programs has largely focused on behavioral metrics, emerging literature suggests that neurofunctional activity may be a more robust predictor of relapse. While drug cue-reactivity in limbic processing regions (including the medial prefrontal cortex (MPFC), insula, and striatum) may predict relapse, activity in executive control regions (including the dorsolateral PFC (DLPFC)) is associated with sustained abstinence . Specifically, individuals that remain abstinent for 3 or more months have higher PFC gray matter integrity and baseline functional activity in their PFC relative to active users or recently abstinent peers . Most of these studies however are cross-sectional and assess these brain regions in isolation rather than as integrated networks.

Through interleaved transcranial magnetic stimulation (TMS) in the MRI environment, it is possible to differentially activate executive control and limbic circuitry by applying pulses of stimulation to the dorsolateral PFC (DLPFC) and MPFC respectively [31]. Extending decades of knowledge about the top-down influence of executive control circuitry on limbic circuitry, functional connectivity analysis revealed that TMS-induced DLPFC activity is negatively correlated with frontal and striatal elements of limbic circuit activity, including the medial and orbital PFC and the caudate. This 'negative' functional connectivity between the DLPFC and limbic regions however, was not present in a cohort of cocaine users with a history of relapse (see Significance). The overarching goal of this longitudinal imaging study is to use the novel probe to determine the relationship between executive and limbic circuit integrity as it relates to immediate and extended outcomes after an intensive outpatient treatment program. This will be achieved by assessing functional connectivity in treatment-seeking cocaine users and non-drug using controls at baseline (Aim1), and after a 28-day cognitive-behavioral treatment program (users only)(Aim 2). The relationship between the integrity of these circuits and clinically meaningful outcome measures will be determines 60 days and 90 days after baseline (Aim 3).

Aim 1: Investigate baseline executive and limbic circuit connectivity in treatment-seeking users and controls. Hypothesis: Interleaved imaging will demonstrate that cocaine users (n=55) have significantly lower % signal change in the DLPFC than controls, lower positive connectivity between the DLPFC (low integrity of executive circuitry) and the dorsal striatum, and lower negative connectivity between the DLPFC and the MPFC (low executive influence on limbic circuitry), suggesting that the DLPFC does not effectively modulate limbic circuitry in cocaine users.

Aim 2: Quantify changes in executive and limbic circuit connectivity that may occur following a 28-day cognitive-behavioral treatment program. Hypothesis: Cocaine users will have an elevation in the % signal change in the DLPFC (relative to Aim1), and the functional connectivity between the DLPFC and the limbic circuitry will increase (elevated influence of executive on limbic circuitry). Secondary hypothesis: This change in functional connectivity will be associated with a change in cognitive control on a battery of tests.

Aim 3: Determine the extent to which functional connectivity at baseline (Aim 1) or after treatment (Aim 2) is related to clinically-relevant metrics of drug use, cognitive control, and sustained connectivity after treatment commencement. Hypothesis: Within the 55 cocaine users, individuals that have the highest DLPFC % signal change or the highest negative correlation coefficient between the DLPFC and MPFC (at baseline and immediately after treatment), will be the individuals with the lowest number of drug positive urines, and will be the most likely to remain in the sample after 60 and 90 days of abstinence.

Study Design

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Study Type :	Observational
Actual Enrollment :	24 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Longitudinal Assessment of Functional Connectivity in Treatment Engaged Cocaine Users
Actual Study Start Date :	August 1, 2015
Actual Primary Completion Date :	June 9, 2019
Actual Study Completion Date :	June 9, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Cocaine hydrochloride

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Cocaine Dependent Individuals with cocaine dependence	Diagnostic Test: magnetic resonance imaging Participants will receive a 60 minute magnetic resonance imaging assessment
Not Cocaine Dependent Individuals without cocaine dependence	Diagnostic Test: magnetic resonance imaging Participants will receive a 60 minute magnetic resonance imaging assessment

Outcome Measures

Primary Outcome Measures :

Percent change of Blood oxygen level dependent (BOLD) signal in executive compared to limbic brain regions [ Time Frame: This will happen at the baseline MRI scan (Day 1), the 2nd MRI scan (1 month after Day 1), the 3rd MRI scan (2 months after Day 1), the 4th MRI scan (3 months after Day 1) ]
Blood oxygen level dependent signal will be measured in several areas of the brain

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	21 Years to 50 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Individuals enrolled in an intensive outpatient rehabilitation program will be invited to enroll in this observational study.

Criteria

Inclusion Criteria:

Currently enrolled in an intensive outpatient treatment program for cocaine dependence

Exclusion Criteria:

metal in the body below the neck
history of traumatic brain injury

Contacts and Locations

Information from the National Library of Medicine

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): NCT03554928

Locations

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United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

Investigators

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Principal Investigator:	Colleen A Hanlon, PhD	Medical University of South Carolina

More Information

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Responsible Party:	Colleen A Hanlon, PhD, Associate Professor, Medical University of South Carolina
ClinicalTrials.gov Identifier:	NCT03554928
Other Study ID Numbers:	33406
First Posted:	June 13, 2018 Key Record Dates
Last Update Posted:	July 23, 2019
Last Verified:	July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Deidentified data will be shared on the NIH neuroimaging biorepository at the conclusion of data analysis
Supporting Materials:	Study Protocol Informed Consent Form (ICF) Analytic Code
Time Frame:	These data will be shared within 6 months of the final enrollment and data analysis.
Access Criteria:	Access is open to the public

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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Substance-Related Disorders Cocaine-Related Disorders Chemically-Induced Disorders Mental Disorders

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