Cerebellar Involvement in Alcohol Use Disorder (AUD)

May 7, 2026 updated by: Johns Hopkins University

Investigation of Cerebellar Involvement in AUD

The goal of this observational and interventional study is to better understand the involvement of the cerebellum in the brain reward system in persons with alcohol use disorder (AUD). The main questions it aims to answer are:

  1. What is the nature of cerebellar input to the ventral tegmental area (VTA) in the brain reward system, and how is it perturbed in AUD?
  2. What is the relationship between measures of cerebellar integrity and magnitude of reward activation to alcohol-related cues in cerebellar, VTA and other brain reward structures?
  3. What is the therapeutic potential of cerebellar transcranial direct current stimulation (tDCS) for modulating alcohol cue reactivity, associated alcohol craving, and cerebellar - VTA functional connectivity in the brain reward system? Persons with AUD will be compared with healthy control participants.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Recent animal studies have provided new evidence that the cerebellum may have a stronger link to the reward system of the brain than was previously recognized. Direct projections from cerebellar deep nuclei (DN) to the ventral tegmental area (VTA) have been identified, and stimulation of these cerebellar afferents to the VTA was found to be rewarding. Such findings raise the possibility that cerebellar dysfunction could contribute substantially to addiction via a cerebellar influence over VTA. Consistent with animal findings, the investigators have found in human functional MRI (fMRI) preliminary data strong cerebellar and VTA activation in response to alcohol cues relative to non-alcohol stimuli in patients with alcohol use disorder (AUD) compared to controls, and close coupling observed between DN and VTA activation. Studying AUD and control participants, this project will address three important questions. The first is: What is the nature of cerebellar input to the VTA, and how is it perturbed in AUD? A number of investigations have suggested that when a stimulus is presented, the cerebellum generates a prediction of events that will follow based on prior associative learning, and then compares predicted and actual outcomes to generate a prediction error. The investigators hypothesize that these functions are disrupted in AUD. The investigators' preliminary data show that when an expected stimulus does not occur, a strong prediction error signal in the form of increased functional connectivity (FC) between cerebellum and its projection target is observed, and the investigators found an analogous increase in DN-VTA FC, that was abnormal in AUD patients, when alcohol pictures were presented. In Aim 1, using fMRI and a monetary incentive task, the investigators will investigate if DN-VTA FC reflects reward prediction and/or positive or negative reward prediction error. The second question is: Is the amount of activation in brain reward centers that is elicited by alcohol stimuli related to the amount of dysfunction in the cerebellum? In Aim 2 the investigators will investigate 2 measures of cerebellar integrity to determine the relationship with the magnitude of alcohol cue related activation in cerebellar, VTA, and other reward structures, and with DN-VTA FC: (1) The timing of the undershoot of the cerebellar hemodynamic response function (HRF), which has been found to be correlated with number of lifetime drinks; and (2) classical eyeblink conditioning, for which the cerebellum is necessary. The third question is: Can abnormal cerebellar activation and FC, as well as alcohol craving, be reduced by non-invasive cerebellar stimulation? In Aim 3, Using fMRI combined with cerebellar transcranial direct current stimulation (tDCS) during a cue reactivity task, the investigators hypothesize that in AUD participants cerebellar and VTA activation will be reduced, DN-VTA FC will be normalized, and alcohol craving will be reduced. The investigators will examine, using both resting state fMRI and psychophysiological interaction analysis, the effects of tDCS on FC among important structures of the reward system as well as on DN-VTA FC. These investigations will lead to a better understanding of the involvement of the cerebellum in AUD, as well as the therapeutic potential of cerebellar modulation.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
122

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: JoAnna Mathena

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Johns Hopkins University School of Medicine
        • Contact:
          • John Desmond, Ph.D.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

25 years to 55 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • completed at least 8 years of education

Exclusion Criteria:

  • Estimated Intelligence Quotient (IQ) < 90
  • less than 5th grade reading level
  • Left handed
  • Non-fluent in English
  • current drug use disorder other than alcohol (except nicotine and caffeine) and or recent drug use in the last 90 days
  • Positive breath alcohol level at time of MRI scan or discrepancies between alcohol biomarker and self-report that cannot be resolved
  • Exhibiting symptoms of alcohol withdrawal on visit 1 assessment
  • Significant current psychiatric distress and or treatment
  • History of any central nervous system disorder, presence of a seizure disorder, or use of anticonvulsant medication in the past 3 months
  • any serious medical condition detected on assessment or by medical record review; or have liver function tests more than three times normal at screening
  • History of metal implantation that would preclude MRI scanning; or other implants, pumps, pacemakers that would be contraindications for MRI scanning
  • Abnormal MRI scan or history of significant closed head trauma
  • Evidence of dementia
  • For women, pregnancy

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: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cathodal cerebellar transcranial direct current stimulation (ctDCS)
For ctDCS, the cathodal (-) electrode will be positioned over the right cerebellum 1 cm below and 3 cm lateral to the inion, and the anodal (+) electrode will be placed on the contralateral supraorbital area (FP2 EEG location).
Procedure: cerebellar transcranial direct current stimulation
TDCS is a safe and non-invasive technique for modulating cortical excitability and behavior. TDCS, delivered via surface electrodes, induces an intracerebral current flow sufficient to achieve changes in cortical excitability. Anodal stimulation up-regulates cortical excitability, while cathodal stimulation decreases excitability.
Experimental: Anodal cerebellar transcranial direct current stimulation (atDCS)
For atDCS, anode/cathode locations are reversed from those of ctDCS..
Procedure: cerebellar transcranial direct current stimulation
TDCS is a safe and non-invasive technique for modulating cortical excitability and behavior. TDCS, delivered via surface electrodes, induces an intracerebral current flow sufficient to achieve changes in cortical excitability. Anodal stimulation up-regulates cortical excitability, while cathodal stimulation decreases excitability.
Sham Comparator: Sham cerebellar transcranial direct current stimulation (stDCS)
For stDCS, the electrodes will be configured randomly as atDCS 50% of the time, and as ctDCS 50% of the time.
Procedure: cerebellar transcranial direct current stimulation
TDCS is a safe and non-invasive technique for modulating cortical excitability and behavior. TDCS, delivered via surface electrodes, induces an intracerebral current flow sufficient to achieve changes in cortical excitability. Anodal stimulation up-regulates cortical excitability, while cathodal stimulation decreases excitability.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Craving for alcohol during the cue reactivity task as assessed by a rating scale
Time Frame: 28 minutes
Participants will view blocks of pictures of alcohol and non-alcohol beverages, as well as control pictures and periods of rest. Participant rating of alcohol craving are obtained during the picture presentations using one of 5 buttons placed under their fingers, where 5 (thumb) = Extreme, 4=Severe, 3=Moderate, 2=Mild, 1=None
28 minutes
Resting state functional connectivity during tDCS
Time Frame: 28 minutes
Participants will rest quietly during tDCS administration
28 minutes
Brain activation to alcohol cues
Time Frame: 28 minutes
Participants will view blocks of pictures of alcohol and non-alcohol beverages, as well as control pictures and periods of rest. Brain activation will be measured from the fMRI signal on alcohol minus non-alcohol conditions.
28 minutes
Brain functional connectivity to alcohol vs non-alcohol cues
Time Frame: 28 minutes
A psychophysiological interaction (PPI) analysis will be used to determine if brain connectivity between the cerebellum and reward areas changes when viewing alcohol versus non-alcohol pictures
28 minutes
Brain activation related to reward prediction during the monetary incentive task
Time Frame: 18 minutes
The monetary incentive task is performed during fMRI scanning. Two different cue symbols (dollar sign vs circle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Brain activation during reward prediction will be measured by the post-cue activation on dollar sign versus circle trials.
18 minutes
Brain functional connectivity related to reward prediction during the monetary incentive task
Time Frame: 18 minutes
The monetary incentive task is performed during fMRI scanning. Two different cue symbols (dollar sign vs circle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Functional connectivity between the cerebellum and reward structures during reward prediction will be measured by a PPI analysis that measures post-cue functional connectivity on dollar sign versus circle trials.
18 minutes
Brain activation to reward prediction error during the monetary incentive task
Time Frame: 18 minutes
Two different symbols (circle vs triangle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Brain activation to reward prediction error will be measured from the activation observed after the participant receives feedback on his/her winnings, by contrasting trials in which reward obtained is equal to the amount expected versus not equal to the amount expected.
18 minutes
brain functional connectivity to reward prediction error during the monetary incentive task
Time Frame: 18 minutes
Two different symbols (circle vs triangle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Functional connectivity between the cerebellum and reward structures to reward prediction error will be measured using a PPI on the connectivity that is observed after the participant receives feedback on his/her winnings, by contrasting trials in which reward obtained is equal to the amount expected versus not equal to the amount expected.
18 minutes
Percentage of trials with a conditioned response during the classical eyeblink conditional task
Time Frame: 21 minutes
Eyeblink conditioning involves pairing a neutral stimulus, e.g. an auditory conditioned stimulus (CS), with an air puff to the eye region. This unconditioned stimulus (US) evokes an unconditioned response (UR) that is detected by measuring the eyeblink. After repeated pairings of the CS and US, participants learn to blink in response to the conditioned stimulus and before air puff onset. The CS-US pairing dependent eyeblink that anticipates the onset of the US is referred to as the conditioned response (CR).
21 minutes
Mean time (in milliseconds) at which peak of conditioned response occurs during the classical eyeblink conditional task
Time Frame: 21 minutes
Eyeblink conditioning involves pairing a neutral stimulus, e.g. an auditory conditioned stimulus (CS), with an air puff to the eye region. This unconditioned stimulus (US) evokes an unconditioned response (UR) that is detected by measuring the eyeblink. After repeated pairings of the CS and US, participants learn to blink in response to the conditioned stimulus and before air puff onset. The CS-US pairing dependent eyeblink that anticipates the onset of the US is referred to as the conditioned response (CR).
21 minutes

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Baseline cerebral blood flow (CBF) measured from a CBF MRI scan
Time Frame: 4 minutes and 40 seconds
Local increases in cerebral blood flow (CBF) that exceed the increase in blood oxygen metabolism (CMRO2) cause a reduction of deoxyhemoglobin leading to a lengthening of the transverse relaxation time T2* and increased MRI signal. CBF is measured as ml/100g tissue/minute.
4 minutes and 40 seconds
Behavioral accuracy during the monetary incentive task
Time Frame: 18 minutes
Two different symbols (circle vs triangle) will cue participants to expect a $1 or $0 reward shortly after they press a button in response to seeing an "X" on the screen. These expectations will be learned in an initial Learning phase, where one symbol is always rewarded with $1 and the other with $0, and participants will be tested to ensure that they have learned the appropriate expectations. This Learning phase will be followed by a Testing phase in which the amount of reward (on reward trials) can be greater than, less than, or equal to expectation. Accuracy will be measured as the percent of trials in which the participant successfully pressed the button only when the X was on the screen
18 minutes

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: John E Desmond, PhD, Johns Hopkins University

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 12, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 7, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 16, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 11, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00337209
  • R01AA030368 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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