Brain Stimulation for Alcohol Misuse

(FLAME Trial)

Overseen By Grace M Elliott, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of North Carolina, Chapel Hill

Must not be taking: Psychotropics, Recreational drugs

Disqualifiers: Substance use disorder, Neurological disease, Psychosis, ADHD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

66 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a non-invasive brain stimulation technique, specifically 10 Hz transcranial alternating current stimulation (tACS), can influence decision-making in individuals with a history of alcohol misuse. The goal is to determine if a single session of brain stimulation can alter brain activity in areas related to habits, potentially reducing habitual behaviors linked to alcohol use. The trial compares real brain stimulation to a placebo version to assess any differences in habit-related decision-making. Individuals with high-risk drinking patterns or frequent binge drinking during their teenage years might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research on innovative treatments for alcohol misuse.

Will I have to stop taking my current medications?

The trial requires that participants do not use psychotropic medications (drugs affecting mood or behavior) in the past month, unless it's an antidepressant with a stable dosage for at least one month. If you are taking other medications, you may need to stop them to participate.

What prior data suggests that alpha-tACS is safe for use in brain stimulation?

Studies have shown that using 10 Hz transcranial alternating current stimulation (tACS) is generally safe for people. In past research, participants experienced tACS without any serious side effects. Most people only felt mild sensations like tingling or itching, which usually went away quickly.

Research shows that tACS has been safely used in studies about brain function, including those related to alcohol use disorders. These studies have not reported any major negative effects, suggesting that the treatment is safe. However, as with any treatment, individual experiences can differ, so discussing any concerns with the research team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of 10 Hz transcranial alternating current stimulation (tACS) for alcohol misuse because it represents a novel approach to targeting brain activity directly. Unlike traditional treatments for alcohol misuse, which often involve medications like disulfiram or naltrexone that affect neurotransmitter systems, tACS uses electrical currents to modulate brain activity non-invasively. This method can potentially alter habitual behaviors associated with alcohol consumption by stimulating specific areas of the brain, such as the prefrontal cortex. Additionally, the non-invasive nature of this technique could provide an alternative for individuals who may not respond well to medication-based therapies.

What evidence suggests that this brain stimulation technique is effective for reducing habitual action selection in hazardous drinkers?

In this trial, participants will receive either 10 Hz transcranial alternating current stimulation (tACS) or sham tACS. Research has shown that 10 Hz tACS might help reduce habitual behaviors in individuals with a history of substance use. Studies have found that alpha-tACS can change brain activity to improve self-control, potentially aiding in better decision-making. This treatment targets the prefrontal cortex, a brain region involved in decision-making and self-control. Previous research suggests that this type of brain stimulation can alter brain function, potentially reducing impulsive behaviors often linked to alcohol misuse. Although more research is needed to confirm these effects, initial findings are promising for those struggling with habitual drinking patterns. ^{1 2 6 7 8}

Who Is on the Research Team?

Charlotte A Boettiger, PhD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for healthy adults who have a history of alcohol use, including those who may binge-drink. Participants will undergo brain stimulation sessions and complete tasks at a lab. They must be willing to provide blood samples and attend MRI sessions.

Inclusion Criteria

Fluent in English

Have a high school diploma or equivalent

I am between 22 and 50 years old.

Exclusion Criteria

Diagnosis of ADHD

Use of psychoactive recreational drugs in the past month (excluding caffeine and alcohol)

I have had brain surgery in the past.

Timeline for a Trial Participant

Screening and Behavioral Training

Participants are screened for eligibility to participate in the trial and undergo initial behavioral training

1 session

1 visit (in-person)

Behavioral Testing and MRI

Participants undergo behavioral testing and an MRI scan session

1 session

1 visit (in-person)

tACS or Sham Stimulation and EEG

Participants receive either 10Hz bi-frontal tACS or sham stimulation during behavioral testing with pre- and post-EEG recording, followed by a second MRI scan session

1 session

1 visit (in-person)

Follow-up

Participants are monitored for changes in habitual action selection and prefrontal GABA:glutamate/glutamine ratio

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 10 Hz transcranial alternating current stimulation (tACS)
• sham transcranial alternating current stimulation (tACS)

Trial Overview The study tests if alpha-tACS, a non-invasive brain stimulation, can influence the prefrontal cortex and change habitual actions related to alcohol use. It compares this method with sham (fake) stimulation to see if there's an actual effect on behavior.

How Is the Trial Designed?

Group I: 10Hz bi-frontal tACS Experimental Treatment 1 Intervention

For Session 3, participants will complete a Habitual Association between Images Task (HABIT) Test Session in the Howell Hall Neurostimulation Core Lab or electroencephalogram (EEG) Core Lab, which is located one floor below the Boettiger Lab. Participants will receive either 10Hz bi-frontal transcranial alternating current stimulation (tACS) or sham tACS. 10 Hz bi-frontal tACS: Alternating current stimulation is delivered by an XCSITE 100 device (Pulvinar Neuro, Chapel Hill, NC), through three conductive carbon-rubber electrodes. Electrodes are placed over the apex of the head (Cz) and the prefrontal cortex bilaterally (F3 and F4). Stimulation is delivered during the second half of the HABIT Test session. Stimulation parameters: 2mA peak-to-peak 10Hz sine-wave flanked by 10 second linear envelope ramps in and out for a total duration of 30 min and 20 seconds.

Group II: sham tACS Placebo Group 1 Intervention

Sham transcranial alternating current stimulation (tACS): The procedure for sham stimulation will be identical, but the actual stimulation will last for 2 minutes instead of 30 minutes. Participants generally report that stimulation is felt most strongly at the beginning of active stimulation, before they adjust to the sensation. Sham stimulation is meant to mimic this progression in terms of tactile salience. Stimulation is delivered for 2 minutes at the beginning of the HABIT reversal task, flanked by 10 second linear envelope ramps. The stimulating electrodes are left on the head until completion of the HABIT task, as is the case in active stimulation. There is no visual or auditory indication to the participant or researcher when the 2-minute sham stimulation period has ended, allowing the sham stimulation condition to feel similar to active stimulation.

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

This study involving 30 adults with substance use disorders demonstrated that transcranial alternating current stimulation (tACS) is feasible and acceptable in a community treatment setting, with a high treatment retention rate of 87%.

Alpha-tACS significantly improved inhibitory control compared to sham stimulation, with a large effect size (d = 0.83), suggesting it may be a promising intervention for enhancing cognitive control in individuals with substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-tACS effect on inhibitory control and feasibility of administration in community outpatient substance use treatment. Daughters, SB., Yi, JY., Phillips, RD., et al.[2023]

Gamma frequency transcranial alternating current stimulation (tACS) significantly enhances and prolongs the effects of intermittent theta-burst stimulation (iTBS) on motor performance in healthy subjects, indicating its potential to boost brain plasticity.

The study found a direct correlation between the effects of gamma tACS and changes in GABA-A-ergic neurotransmission, suggesting that this method could be a promising strategy for neurorehabilitation by improving responses to plasticity-inducing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Boosting the LTP-like plasticity effect of intermittent theta-burst stimulation using gamma transcranial alternating current stimulation. Guerra, A., Suppa, A., Bologna, M., et al.[2022]

A randomized, double-blind, placebo-controlled trial will evaluate the efficacy of transcranial direct current stimulation (tDCS) in reducing alcohol consumption among 340 participants with alcohol use disorders across 14 centers in France and Monaco.

The study aims to assess not only the reduction in alcohol intake but also improvements in craving, mood, quality of life, and cognitive function, highlighting the potential of tDCS as a novel treatment for addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of transcranial direct current stimulation (tDCS) in reducing consumption in patients with alcohol use disorders: study protocol for a randomized controlled trial. Trojak, B., Soudry-Faure, A., Abello, N., et al.[2018]

Transcranial direct current stimulation (tDCS) and deep brain stimulation (DBS) show limited effectiveness in treating alcohol use disorder, with high relapse rates of 50-70%, indicating that these methods may not provide long-term solutions.

Baclofen, particularly in higher doses for severe alcohol use disorder, has shown promising results in larger studies, with 92% of patients reporting craving suppression and lower relapse rates, although side effects like dizziness and insomnia remain a concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation Therapies for Alcohol Addiction: A Literature Review. Azevedo, CA., Mammis, A.[2022]

Bilateral 10-Hz transcranial alternating current stimulation (10Hz-tACS) of the dorsolateral prefrontal cortex can reduce habitual action-selection in individuals with a history of substance use disorders (SUDs), suggesting a potential nonpharmacological treatment for addiction.

The effectiveness of 10Hz-tACS in reducing habitual actions was found to be influenced by the duration of substance abuse, with longer addiction histories showing greater reductions in perseverative errors, indicating that chronic substance use alters neural circuit dynamics that can be modified by stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addiction history moderates the effect of prefrontal 10-Hz transcranial alternating current stimulation on habitual action selection. McKim, TH., Dove, SJ., Robinson, DL., et al.[2022]

Transcranial direct current stimulation (tDCS) applied to the dorsolateral prefrontal cortex (DLPFC) significantly reduced alcohol craving in 13 patients with alcohol dependence when exposed to alcohol cues, compared to sham stimulation (p<0.0001).

The study suggests that tDCS not only decreases craving but also prevents further increases in craving from alcohol cues, indicating its potential as a rapid and effective treatment strategy for managing alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. Boggio, PS., Sultani, N., Fecteau, S., et al.[2022]

In a clinical trial involving alcohol use disorder patients, 10 sessions of transcranial direct current stimulation (tDCS) significantly reduced alcohol craving scores compared to a sham treatment, with a large effect size of 1.1 for the real tDCS group.

The study found that 72.7% of patients receiving real tDCS remained abstinent from alcohol after 3 months, while 72.2% of the sham group relapsed, suggesting that tDCS may be an effective adjunctive treatment for reducing relapse in alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple Sessions of Transcranial Direct Current Stimulation (tDCS) Reduced Craving and Relapses for Alcohol Use: A Randomized Placebo-Controlled Trial in Alcohol Use Disorder. Klauss, J., Anders, QS., Felippe, LV., et al.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33356905/

Addiction history moderates the effect of prefrontal 10-Hz ... Here, we tested the effect of bilateral 10-Hz transcranial alternating current stimulation (10Ηz-tACs) of the dorsolateral prefrontal cortex on ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0001691825002525

Effectiveness of transcranial alternating current stimulation ... This study investigates the impact of transcranial alternating current stimulation (tACS) at 10 Hz and individual alpha frequencies (IAF), along with cognitive ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8815795/

Alpha-tACS effect on inhibitory control and feasibility of ... Alpha-tACS is designed to modulate alpha oscillations by applying a 10 Hz stimulation current waveform and has demonstrated feasibility and efficacy in clinical ...

4. withpower.com withpower.com/trial/phase-alcohol-drinking-6-2024-bd336

Brain Stimulation for Alcohol Misuse (FLAME Trial) Research suggests that 10 Hz transcranial alternating current stimulation (tACS) can help reduce habitual actions in people with a history of substance use ...

5. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/07/NCT05907707/Prot_SAP_000.pdf

Effects of Transcranial Alternating Current Stimulation ( ... • Indication for alcohol use disorder: AUDIT score (Alcohol Use Disorders Identification Test; screening for unhealthy alcohol use) ≥7 for ...

6. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1419243/full

a systematic review of treatment parameters and outcomes This systematic review aimed to compile human research on tACS for neuropsychiatric disorders to delineate typical treatment parameters for these conditions ...

7. nature.com nature.com/articles/s41398-019-0439-0

Double-blind, randomized pilot clinical trial targeting alpha ... Here we evaluated the feasibility and efficacy of transcranial alternating current stimulation (tACS) at 10 Hz, which we hypothesized would ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S187874792301382X

Non-invasive Brain Stimulation for Alcohol Use Disorders Currently available data generally supports the use of non-invasive brain stimulation as a near-term treatment for alcohol use disorder.