Alcohol Use DisorderNCT04971681
Frontal-Striatal Reward Circuit Neuromodulation and Alcohol Self-Administration
A study testing Low frequency repetitive transcranial magnetic stimulation (rTMS) in people with Alcohol Use Disorder, run by Indiana University at 1 site in United States.
Trial summary
This will be a single site randomized, 2-session, within-subject cross-over design pilot study. 20 enrolled (of 30 consented) subjects reporting varying levels of binge and high intensity drinking, defined as at least 2 episodes of drinking 4 (for women) or 5 (for men) drinks on an occasion over the last 5 weeks… Read more about this study
- Who is it for?
- Ages 21 to 35 years
- Conditions the study is for
- Alcohol Use Disorder
- What is being tested?
- Low frequency repetitive transcranial magnetic stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2021to 2 Jun 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Overtly healthy men and women aged 21 - 35
- Able to give informed consent
- Able to understand/complete questionnaires and procedures in English
- Willing and able to adhere to the study schedule
- At least 2 binge drinking events (at least 4 or 5 drinks on a drinking day for women and men respectively over the last 5 weeks, unless determined by study physicians that drinking history meets study objectives
- Have venous access sufficient to allow blood sampling
Who cannot join
- Pregnant or breast-feeding
- Desire to be treated for any substance use disorder or court ordered to not drink alcohol
- Medical disorders or other conditions, such as lifetime history of a seizure, including history of Electroconvulsive therapy (ECT) but excluding febrile seizures and those induced by substance withdrawal, that may influence study outcome or subject safety
- First degree relative with idiopathic epilepsy or other seizure disorder
- Diagnostic and Statistical Manual (DSM) 5 Disorders (non-AUD) or current/history of neurological disease of cerebral origin, or head injury with > 20 min loss of consciousness, if determined by the study physicians to affect subject safety or data integrity
- Positive urine drug screen for amphetamines/ methamphetamines, barbiturates, benzodiazepines, cocaine, opiates, or phencyclidine if determined by the study physicians to adversely affect subject safety or data integrity
Show all 10Show fewer
- Medications (past 30 days) that could influence subject data/subject safety (e.g. antidepressants, antipsychotics, benzodiazepines, etc.) as determined by study physicians
- Positive BrAC reading at beginning of any study session
- Actively suicidal (for example, any suicide attempts within the past 3 months or any current suicidal intent, including a plan) or are at serious suicidal risk, by clinical judgment of the study physicians
- Any condition for which the study physicians determine it is unsafe or not prudent to enroll a subject
Trial locations and contacts
1 site in 1 country.
About this study
This will be a single site randomized, 2-session, within-subject cross-over design pilot study. 20 enrolled (of 30 consented) subjects reporting varying levels of binge and high intensity drinking, defined as at least 2 episodes of drinking 4 (for women) or 5 (for men) drinks on an occasion over the last 5 weeks, (unless determined by PI that drinking history meets study objectives), will be enrolled. Subjects will be randomized to undergo one session of repetitive transcranial magnetic stimulation (rTMS) or sham immediately followed by the investigators rate control intravenous (IV) alcohol self-administration (ASA) paradigm. Subjects will then return 7-14 days later and undergo the same sequence of events with the opposite intervention (i.e. rTMS or sham) from session 1.
Read the detailed description
This pilot study intends to address the critical unmet need to develop novel treatments for alcohol use disorder (AUD), such as repetitive transcranial magnetic stimulation (rTMS), that directly impact drinking behavior. Binge drinking and high intensity drinking, or consumption meeting at least binge criteria, is a high-risk alcohol self-administration (ASA) pattern associated with the binge-intoxication stage of AUD and the rewarding effects of alcohol. The investigators propose to quantify the impact of medial prefrontal cortex (mPFC) rTMS on ASA using the investigators novel "rate-control" paradigm. The rate control paradigm allows subjects to determine how quickly their breath alcohol concentration (BrAC) will change (increase, decrease, or stay the same) over the next 3-5 minute epoch, at the end of which brief computer-assisted assay of craving for alcohol and subjective response attributed to alcohol's effect on stimulation, sedation, liking and well-being in a manner comparable to the Brief Biphasic Alcohol Effects Scale (BAES). Each assay requires less than 20 seconds to complete and will be administered during the last ~0.5 minutes of alcohol delivery but before selection of the next rate of exposure. The ensemble provides detailed self-administered time course of alcohol exposure and corresponding time-stamped series of quantified perceptions for analysis. This approach has demonstrated sensitivity in associating self-reported high intensity drinking and the time until a binge alcohol exposure of 80 milligrams per decilitre (mg/dL).
The investigators premise is that clinically impactful neuromodulation should change ASA. Coupling rTMS to a laboratory-assessed ASA paradigm could document causal changes in drinking behavior attributable to modulation of specific neural circuits. The goal of this project is to generate preliminary data supporting the investigators central hypothesis - rTMS targeting to the mPFC, a primary cortical input to the frontal-striatal reward (FSR) circuit, will decrease the rate of alcohol self-administration.
- Conditions
- Alcohol Use Disorder
- Being tested
- Low frequency repetitive transcranial magnetic stimulation (rTMS), Sham
- Medical subject headings
- Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low frequency repetitive transcranial magnetic stimulation (rTMS)Device
Subjects will receive one session of low frequency repetitive transcranial magnetic stimulation (rTMS) targeting the medial prefrontal cortex (mPFC), within the following stimulation parameters: Continuous 20-minute train of 1 Hz rTMS, at 110% of motor threshold (MT), for a total of 1200 pulses
ShamDevice
The active and sham functions share the same acoustic properties and sham mimics cutaneous stimulation, facilitating double-blinding.
| Study group | Role | What they receive |
|---|---|---|
| Low frequency repetitive transcranial magnetic stimulation (rTMS) | Experimental | Low frequency repetitive transcranial magnetic stimulation (rTMS) Receives: Device: Low frequency repetitive transcranial magnetic stimulation (rTMS); Device: Sham |
| Sham rTMS Stimulation | Sham comparator | Sham rTMS Stimulation Receives: Device: Low frequency repetitive transcranial magnetic stimulation (rTMS); Device: Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
T80
The amount of time subjects take to self-administer enough alcohol to raise their breath alcohol concentration (BrAC) to 80 mg/dL
Measured: 90 min
Secondary outcomes (1)
Alcohol Consumption (Drinks/Week)
Alcohol consumption as measured by Time Line Follow Back (TLFB) comparing drinking baseline (5 weeks prior to study) with post-treatment during the 5-week follow-up period. The Timeline Follow-back (TLFB) is uses a calendar to assess a subject's retrospective estimates of their daily drinking.
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2021
- Study start8 Oct 2021
- Primary completion25 Apr 2022
- Study completion2 Jun 2022
Why it stopped: Enrollment paused when our alcohol supplier recalled and suspended manufacture of the product. When production resumed, there was not enough time remaining to successfully resume recruitment. We will examine the outcomes with the existing sample.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alcohol Use DisorderStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Responsible party
- Principal investigator, Susan K. Conroy, Indiana University
- Investigators
- Susan Conroy, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04971681
- Sponsor's protocol ID
- 11511
- Other IDs
- P60AA007611
- Status last verified
- Jan 2025
- First submitted
- 12 Jul 2021
- Last updated
- 13 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Frontal-Striatal Reward Circuit Neuromodulation and Alcohol Self-Administration
- ClinicalTrials.gov ID
- NCT04971681
- Acronym / sponsor ID
- 11511
- Conditions
- Alcohol Use Disorder
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment paused when our alcohol supplier recalled and suspended manufacture of the product. When production resumed, there was not enough time remaining to successfully resume recruitment. We will examine the outcomes with the existing sample.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute on Alcohol Abuse and Alcoholism (NIAAA)
- Study start
- 8 Oct 2021 (actual)
- Primary completion
- 25 Apr 2022 (actual)
- Study completion
- 2 Jun 2022 (actual)
- First posted
- 21 Jul 2021 (actual)
- Results
- Posted 16 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This will be a single site randomized, 2-session, within-subject cross-over design pilot study. 20 enrolled (of 30 consented) subjects reporting varying levels of binge and high intensity drinking, defined as at least 2 episodes of drinking 4 (for women) or 5 (for men) drinks on an occasion over the last 5 weeks, (unless determined by PI that drinking history meets study objectives), will be enrolled. Subjects will be randomized to undergo one session of repetitive transcranial magnetic stimulation (rTMS) or sham immediately followed by the investigators rate control intravenous (IV) alcohol self-administration (ASA) paradigm. Subjects will then return 7-14 days later and undergo the same sequence of events with the opposite intervention (i.e. rTMS or sham) from session 1.
Detailed description
This pilot study intends to address the critical unmet need to develop novel treatments for alcohol use disorder (AUD), such as repetitive transcranial magnetic stimulation (rTMS), that directly impact drinking behavior. Binge drinking and high intensity drinking, or consumption meeting at least binge criteria, is a high-risk alcohol self-administration (ASA) pattern associated with the binge-intoxication stage of AUD and the rewarding effects of alcohol. The investigators propose to quantify the impact of medial prefrontal cortex (mPFC) rTMS on ASA using the investigators novel "rate-control" paradigm. The rate control paradigm allows subjects to determine how quickly their breath alcohol concentration (BrAC) will change (increase, decrease, or stay the same) over the next 3-5 minute epoch, at the end of which brief computer-assisted assay of craving for alcohol and subjective response attributed to alcohol's effect on stimulation, sedation, liking and well-being in a manner comparable to the Brief Biphasic Alcohol Effects Scale (BAES). Each assay requires less than 20 seconds to complete and will be administered during the last ~0.5 minutes of alcohol delivery but before selection of the next rate of exposure. The ensemble provides detailed self-administered time course of alcohol exposure and corresponding time-stamped series of quantified perceptions for analysis. This approach has demonstrated sensitivity in associating self-reported high intensity drinking and the time until a binge alcohol exposure of 80 milligrams per decilitre (mg/dL).
The investigators premise is that clinically impactful neuromodulation should change ASA. Coupling rTMS to a laboratory-assessed ASA paradigm could document causal changes in drinking behavior attributable to modulation of specific neural circuits. The goal of this project is to generate preliminary data supporting the investigators central hypothesis - rTMS targeting to the mPFC, a primary cortical input to the frontal-striatal reward (FSR) circuit, will decrease the rate of alcohol self-administration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low frequency repetitive transcranial magnetic stimulation (rTMS) | Experimental | Device: Low frequency repetitive transcranial magnetic stimulation (rTMS), Device: ShamLow frequency repetitive transcranial magnetic stimulation (rTMS) |
| Sham rTMS Stimulation | Sham comparator | Device: Low frequency repetitive transcranial magnetic stimulation (rTMS), Device: ShamSham rTMS Stimulation |
Who may qualify
- Ages
- 21 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Overtly healthy men and women aged 21 - 35
- Able to give informed consent
- Able to understand/complete questionnaires and procedures in English
- Willing and able to adhere to the study schedule
- At least 2 binge drinking events (at least 4 or 5 drinks on a drinking day for women and men respectively over the last 5 weeks, unless determined by study physicians that drinking history meets study objectives
Key exclusion criteria (10 listed)
- Pregnant or breast-feeding
- Desire to be treated for any substance use disorder or court ordered to not drink alcohol
- Medical disorders or other conditions, such as lifetime history of a seizure, including history of Electroconvulsive therapy (ECT) but excluding febrile seizures and those induced by substance withdrawal, that may influence study outcome or subject safety
- First degree relative with idiopathic epilepsy or other seizure disorder
- Diagnostic and Statistical Manual (DSM) 5 Disorders (non-AUD) or current/history of neurological disease of cerebral origin, or head injury with > 20 min loss of consciousness, if determined by the study physicians to affect subject safety or data integrity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low frequency repetitive transcranial magnetic stimulation (rTMS)Subjects will receive one session of low frequency repetitive transcranial magnetic stimulation (rTMS) targeting the medial prefrontal cortex (mPFC), within the following stimulation parameters: Continuous 20-minute train of 1 Hz rTMS, at 110% of motor threshold (MT), for a total of 1200 pulses | Device | Low frequency repetitive transcranial magnetic stimulation (rTMS), Sham rTMS Stimulation |
| ShamThe active and sham functions share the same acoustic properties and sham mimics cutaneous stimulation, facilitating double-blinding. | Device | Low frequency repetitive transcranial magnetic stimulation (rTMS), Sham rTMS Stimulation |
Primary outcome
T80
Time frame: 90 min
The amount of time subjects take to self-administer enough alcohol to raise their breath alcohol concentration (BrAC) to 80 mg/dL
1 secondary outcome
Alcohol Consumption (Drinks/Week)
Time frame: 5 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan Conroy, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low frequency repetitive transcranial magnetic stimulation (rTMS) in people with Alcohol Use Disorder, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
T80 (time frame: 90 min). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2025.