Clinical Intervention in Alcohol Use Disorder

April 24, 2023 updated by: University of Minnesota

Combining Neuro-Imaging and Non-Invasive Brain Stimulation for Clinical Intervention in Alcohol Use Disorder

Long-term abstinence from alcohol is supported by a compensatory mechanism in functional brain connectivity, a potential brain biomarker that could be an intervention target. These findings provide a compelling case to explore whether this brain biomarker can be modulated to enhance patients' ability to remain abstinent. There is a need to investigate methods that can be used to increase functional brain connectivity. The overall objective of this proposal is to enhance brain functional connectivity in short-term abstinent alcoholics as a therapeutic intervention that supports abstinence.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The relapsing nature of alcoholism is a major obstacle to successful treatment. About 60% of those entering treatment will relapse within one year. To improve treatment outcome, new interventions targeting the underlying brain biomarkers of relapse vulnerability hold significant promise in reducing this critical public health problem. Using resting functional magnetic resonance imaging (fMRI) the investigators have identified brain biomarkers that support long-term abstinence. Cross-sectional and longitudinal findings provide evidence that higher functional connectivity (FC), particularly between nucleus accumbens (NAcc) and dorsolateral prefrontal cortex (DLPFC), is a potential brain biomarker that supports abstinence. Long-term abstinent alcoholics (7 years of abstinence) have higher resting FC between NAcc and DLPFC when compared to controls. Short-term abstinent alcoholics (11 weeks of abstinence) have intermediate FC (lower than long-term abstinent alcoholics and higher than controls). Further, lower FC between NAcc and DLPFC at 11 weeks of abstinence can be a predictor of subsequent relapse (with 74% accuracy). Moreover, in a pilot longitudinal FC study examining resting FC of NAcc at 5 and 13 weeks of abstinence in individuals with substance use disorder, the investigators found that FC between NAcc and DLPFC decreased from 5 to 13 weeks of abstinence in subsequent relapsers, while it increased in subsequent abstainers. Based on the above, the investigators believe that long-term abstinence is supported by a compensatory mechanism that mediates proper executive function over reward (mediated by PFC-NAcc FC), a potential brain biomarker that could be an intervention target. These findings provide a compelling case to explore whether this brain biomarker can be modulated to enhance patients' ability to remain abstinent. There is a need to investigate methods that can be used to increase FC between DLPFC and NAcc.

Cognitive flexibility, the ability to change maladaptive behavior, depends on DLPFC input to NAcc. DLPFC transmits reward representations to NAcc through glutamatergic projections that guide goal-directed behavior. If DLPFC fails to activate when required, a common observation in substance use disorder, target neurons in the NAcc core do not receive critical information needed to select the appropriate outcome, causing acquired maladaptive response patterns to persist (e.g. drug consumption). Higher FC between DLPFC and NAcc may be achieved by stimulating DLPFC while subjects perform a task that requires cognitive flexibility, the reversal learning task.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modulate brain connectivity. DLPFC stimulation may increase input to NAcc to facilitate proper selection of goal-directed behavior and may also decrease craving in individuals with substance use disorder.

Genetics and treatment response: A source of treatment response variability could stem from differences between participants in baseline genetic profiles or epigenetic changes over the course of treatment. Genetic polymorphisms, especially in genes important for neuroplasticity, may also mediate neuroplastic changes underlying the effects of tDCS, as has been demonstrated with gene BDNF. In light of these genetic influences on key tenants of the study - i.e. treatment response in alcohol use disorder and psychological effects of tDCS - the investigators will collect genetic samples from participants to determine whether genetic or epigenetic variations may affect response to the cognitive training and tDCS intervention. As the secondary aim, participants will be given the choice in the consent form to opt in or out of the genetic sampling procedure.

In a double-blind randomized design, up to 100 abstinent (2 weeks abstinent) individuals with alcohol use disorder (AUD) recruited from Lodging Plus Program will receive 10 sessions (2 sessions per day for 5 days) of either (i) transcranial direct current stimulation (tDCS) to PFC or (ii) sham-tDCS. All subjects will perform the reversal learning task during tDCS intervention (active or sham) to prime the engagement of the NAcc-PFC brain circuit that mediates cognitive flexibility. Rest fMRI and craving measures will be collected before the first and after the last day of tDCS sessions. Monthly follow-up interviews will be conducted for 6 months after study completion to query relapse status. Dependent variables will be (i) change in NAcc-PFC FC between 2 and 3 weeks of abstinence, (ii) change in craving scores between 2 and 3 weeks of abstinence and (iii) relapse status ~8 months after study participation. Aim 1: To investigate whether NAcc-PFC FC can be modulated, the investigators will compare magnitude and durability of change in NAcc-PFC FC between active-tDCS and sham-tDCS groups. Aim 2: To determine if PFC stimulation has a short-term effect on behavior related to clinical outcome, the investigators will compare change in craving scores (difference in craving scores between 2 and 3 weeks of abstinence) between active-tDCS and sham-tDCS groups. Aim 3: To correlate neuromodulation intervention with long-term clinical outcome, the investigators will record craving and relapse status during the ~8 months following treatment discharge. The investigators will examine the relationship between change in NAcc-PFC FC between 2 and 3 weeks of abstinence and subsequent (i) monthly craving scores and (ii) relapse status. Aim 4: Examine relationship between genetic variants, epigenetic changes and treatment outcome (e.g. durability, functional connectivity).

Study Type

Interventional

Enrollment (Actual)

86

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Jazmin Camchong, PhD
  • Phone Number: (612) 624-0134

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55414
        • University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • up to 75 abstinent individuals (18-65 years old; 2 weeks of abstinence) who meet DSM-V criteria for alcohol use disorder (AUD) will be recruited from the Lodging Plus Program, part of University of Minnesota Medical Center
  • This 28-day program provides a supervised environment to treat alcoholism in which patients receive random drug/alcohol screenings daily. Lodging Plus has 50 beds and admits an average of 20 patients per week and 59% of patients admitted have a diagnosis of alcohol use disorder.

Inclusion criteria:

  • ability to provide written consent and comply with study procedures
  • meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria for AUD. Subjects may have current comorbid drug use, but their primary substance use disorder diagnosis needs to be based on alcohol use. Subjects must have the intention to remain in program until the end of the study (3 weeks). Vulnerable populations will not be included

Exclusion Criteria:

  • any medical condition or treatment with neurological sequelae (i.e. stroke, tumor, loss of consciousness of more than 30 min, HIV)
  • a head injury resulting in a skull fracture or loss of consciousness exceeding 30 minutes (i.e., moderate or severe TBI)
  • any contraindications for tDCS or MRI scanning (tDCS contraindications: history of seizures; MRI contraindications; metal implants, pacemakers or any other implanted electrical device, injury with metal, braces, dental implants, non-removable body piercings, pregnancy, breathing or moving disorder.)
  • any primary psychotic disorder (e.g. schizophrenia, schizoaffective disorder). Participants with other treated and stable psychiatric disorders will be included.
  • presence of a condition that would render study measures difficult or impossible to administer or interpret
  • age outside the range of 18 to 65
  • primary current substance use disorder diagnosis on a substance other than alcohol except for caffeine or nicotine
  • clinical evidence of Wernicke-Karsakoff syndrome
  • left handedness
  • entrance to the treatment program. under court mandate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: active tDCS
Subjects that are randomly assigned to this arm will receive 10 active transcranial direct current stimulation (tDCS) sessions
Device: Transcranial Direct Current Stimulation (tDCS)
tDCS will be performed with Neuroelectrics Starstim Enobio 20, a non-invasive investigational device that has been labeled as a non-significant risk device by the FDA. This study is regulated by the FDA as an Abbreviated IDE. It has built-in safety mechanisms which allow for immediate cessation of stimulation if the subject becomes uncomfortable. The current will be administered via two electrode sponges for 25 mins with 1-2 milliamperes. These administration protocols are in line with protocols that have outlined safe administration (Nitsche 2007; 2008). No side-effects have been reported with the exception of slight itching under the electrode and occasional occurrence of headache, fatigue, or nausea (Poreisz 2007). Electrodes placement: dorsolateral prefrontal cortex (DLPFC); cathode on left DLPFC, anode on right DLPFC.
Other Names:
  • Starstim
Sham Comparator: sham tDCS
Subjects randomly assigned to sham-tDCS (transcranial direct current stimulation) will receive very low current stimulation at beginning and end of session, mimicking the feeling of current stimulation in the scalp, but not reaching levels that will stimulate brain function.
Device: Transcranial Direct Current Stimulation (tDCS)
tDCS will be performed with Neuroelectrics Starstim Enobio 20, a non-invasive investigational device that has been labeled as a non-significant risk device by the FDA. This study is regulated by the FDA as an Abbreviated IDE. It has built-in safety mechanisms which allow for immediate cessation of stimulation if the subject becomes uncomfortable. The current will be administered via two electrode sponges for 25 mins with 1-2 milliamperes. These administration protocols are in line with protocols that have outlined safe administration (Nitsche 2007; 2008). No side-effects have been reported with the exception of slight itching under the electrode and occasional occurrence of headache, fatigue, or nausea (Poreisz 2007). Electrodes placement: dorsolateral prefrontal cortex (DLPFC); cathode on left DLPFC, anode on right DLPFC.
Other Names:
  • Starstim

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Brain Functional Connectivity
Time Frame: 1 week
Measured by fMRI scans
1 week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between functional connectivity change and craving scores
Time Frame: approximately 1 week
Craving scores from various self report questionnaires in active vs. sham groups and functional connectivity between them.
approximately 1 week
Correlation between functional connectivity change and clinical outcome
Time Frame: 8 months
Relapse status at 8 month follow up in active and sham groups
8 months
Correlation between genetic variants
Time Frame: Approximately 8 months
Using saliva collection to analyze genetic variations in groups that relapse and groups that do not
Approximately 8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Minnesota

Collaborators

National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institutes of Health (NIH)

Investigators

  • Principal Investigator: Jazmin Camchong, PhD, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 7, 2016

Primary Completion (Actual)

November 17, 2022

Study Completion (Actual)

November 17, 2022

Study Registration Dates

First Submitted

June 13, 2014

First Submitted That Met QC Criteria

June 17, 2014

First Posted (Estimate)

June 20, 2014

Study Record Updates

Last Update Posted (Actual)

April 25, 2023

Last Update Submitted That Met QC Criteria

April 24, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PSYCH-2016-22561
  • K01AA026349 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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