Transcranial Stimulation for Alcoholism

Overseen By JoAnna Mathena

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Johns Hopkins University

Must not be taking: Anticonvulsants

Disqualifiers: Drug use disorder, Psychiatric distress, CNS disorder, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

122 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using anticonvulsant medication, you must not have used it in the past 3 months to participate.

What data supports the effectiveness of the treatment Cerebellar Transcranial Direct Current Stimulation for alcoholism?

Research on transcranial direct current stimulation (tDCS) shows it can reduce alcohol cravings and improve quality of life in alcohol-dependent individuals. Studies have also found that tDCS targeting the dorsolateral prefrontal cortex (a brain area involved in decision-making) can decrease relapse rates and improve decision-making in addiction disorders. ^{1 2 3 4 5}

Is transcranial direct current stimulation (tDCS) of the cerebellum safe for humans?

Research shows that cerebellar tDCS is generally safe for humans, with no serious adverse effects reported in studies involving over 33,200 sessions and 1,000 subjects, including vulnerable populations. It has been well-tolerated in both adults and children, with no reports of irreversible injury. ^{6 7 8 9 10}

How does transcranial stimulation differ from other treatments for alcoholism?

Transcranial direct current stimulation (tDCS) is a unique treatment for alcoholism because it involves non-invasive electrical stimulation of the brain, specifically targeting the prefrontal cortex, which can reduce the risk of alcohol relapse and improve quality of life. Unlike traditional treatments that may involve medication or therapy, tDCS uses electrical currents to modulate brain activity, offering a novel approach to managing alcohol dependence. ^{2 9 11 12 13}

Research Team

John E Desmond, PhD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for individuals with Alcohol Use Disorder who have completed at least 8 years of education. It's not suitable for left-handed people, non-native English speakers, those with serious medical conditions or liver issues, metal implants incompatible with MRI scans, pregnant women, low IQ (<90), current drug use (except nicotine/caffeine), or central nervous system disorders.

Inclusion Criteria

Completed at least 8 years of education

Exclusion Criteria

Non-native English speaker

I have not had any brain disorders, seizures, or taken seizure medications recently.

Left handed

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Observational and Interventional Study

Participants undergo fMRI and tDCS to study cerebellar involvement in AUD

4-6 weeks

Multiple visits for fMRI and tDCS sessions

Follow-up

Participants are monitored for changes in brain activation and connectivity post-intervention

4 weeks

Treatment Details

Interventions

• Cerebellar Transcranial Direct Current Stimulation

Trial Overview The study investigates the cerebellum's role in the brain reward system affected by AUD. It examines how cerebellar input to the VTA is altered in AUD and explores if cerebellar transcranial direct current stimulation can reduce alcohol craving and affect brain connectivity.

Participant Groups

Group I: Cathodal cerebellar transcranial direct current stimulation (ctDCS) Experimental Treatment 1 Intervention

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).

Group II: Anodal cerebellar transcranial direct current stimulation (atDCS) Experimental Treatment 1 Intervention

For atDCS, anode/cathode locations are reversed from those of ctDCS..

Group III: Sham cerebellar transcranial direct current stimulation (stDCS) Placebo Group 1 Intervention

For stDCS, the electrodes will be configured randomly as atDCS 50% of the time, and as ctDCS 50% of the time.

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

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]

In a phase II clinical trial with 33 severe alcoholics, those receiving active transcranial direct current stimulation (tDCS) had a significantly lower relapse rate (50% abstinent) compared to the sham group (11.8% abstinent) after six months, indicating its potential efficacy in reducing relapse risk.

Participants in the tDCS group reported improved quality of life, particularly in the environment domain, suggesting that tDCS not only helps with abstinence but may also enhance overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. Klauss, J., Penido Pinheiro, LC., Silva Merlo, BL., et al.[2016]

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]

A single session of Transcranial Direct Current Stimulation (tDCS) did not significantly reduce drug craving in methamphetamine addicts, indicating that more sessions or different protocols may be needed for craving reduction.

However, tDCS significantly improved cognitive inhibition, particularly with the protocol involving right DLPFC cathodal and left DLPFC anodal stimulation, which is crucial for helping individuals resist cravings during addiction recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Different Transcranial Direct Current Stimulation (tDCS) Protocols on Drug Craving and Cognitive Functions in Methamphetamine Addicts. Rezvanian, S., Saraei, M., Mohajeri, H., et al.[2022]

In a study involving 59 patients with cocaine use disorder, transcranial Direct Current Stimulation (tDCS) did not significantly reduce the number of cocaine use days or craving levels compared to a sham treatment.

However, among crack cocaine users, those receiving active tDCS showed a reduced relapse rate compared to those receiving sham treatment, suggesting potential benefits for this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-session electrical neuromodulation effects on craving, relapse and cognitive functions in cocaine use disorder: A randomized, sham-controlled tDCS study. Verveer, I., van der Veen, FM., Shahbabaie, A., et al.[2021]

Transcranial direct current stimulation (tDCS) shows promise in improving motor function in patients with cerebellar ataxia, particularly in those with less severe impairments, based on a review of 81 patients across various studies.

Improvements were noted in clinical measures of cerebellar deficits, such as gait and coordination, suggesting that tDCS may enhance brain plasticity and restore motor pathways, although more extensive research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The clinical application of transcranial direct current stimulation in patients with cerebellar ataxia: a systematic review. Orrù, G., Cesari, V., Conversano, C., et al.[2022]

In a pilot study involving seven children with autism spectrum disorder (ASD), 20 sessions of transcranial direct current stimulation (tDCS) to the right cerebellar lobe resulted in a 25% mean reduction in overall ASD symptoms, particularly improving social withdrawal and hyperactivity.

The treatment was well tolerated with no serious adverse events reported, and it also showed potential benefits in reducing tics and improving sleep and mood, suggesting that cerebellar tDCS could be a safe and effective intervention for managing ASD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorder: A Pilot Study on Efficacy, Feasibility, Safety, and Unexpected Outcomes in Tic Disorder and Epilepsy. D'Urso, G., Toscano, E., Sanges, V., et al.[2022]

Transcranial Direct Current Stimulation (tDCS) has been shown to be safe, with no reports of Serious Adverse Effects or irreversible injuries across over 33,200 sessions involving more than 1,000 subjects, including vulnerable populations.

Safety assessments indicate that the current densities used in conventional tDCS (≤4 milliamperes) are significantly lower than those that could potentially cause brain injury, suggesting that tDCS protocols are well within safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Bikson, M., Grossman, P., Thomas, C., et al.[2022]

Cerebellar transcranial direct current stimulation (tDCS) is a safe and non-invasive method that can induce lasting changes in cerebellar function, affecting both motor and non-motor skills in healthy individuals.

Preliminary evidence suggests that cerebellar tDCS may also be a promising therapeutic option for patients with cerebellar disorders, as recent modeling studies indicate that the technique effectively targets cerebellar neurons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar tDCS: how to do it. Ferrucci, R., Cortese, F., Priori, A.[2022]

A meta-analysis of 32 sham-controlled studies showed that both anodal and cathodal transcranial direct current stimulation (tDCS) to the cerebellum can effectively alter motor and cognitive performance in healthy individuals.

The study found no significant differences in effects based on the polarity of tDCS, suggesting that while tDCS can target cerebellar functions, the expected outcomes may not depend on whether the stimulation is anodal or cathodal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Human Cerebellum with Transcranial Direct Current Stimulation to Modulate Behavior: a Meta-Analysis. Oldrati, V., Schutter, DJLG.[2022]

Transcranial Direct Current Stimulation (tDCS) is gaining attention for its potential to modulate cerebellar function, which is important due to the cerebellum's dense neuron population and its connections to motor and cognitive areas.

Despite the promise of tDCS and its comparison to Transcranial Alternating Current Stimulation (tACS), there is a lack of large, well-designed clinical trials to clearly establish their efficacy in treating cerebellar disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

tDCS of the Cerebellum: Where Do We Stand in 2016? Technical Issues and Critical Review of the Literature. van Dun, K., Bodranghien, FC., Mariën, P., et al.[2022]

Transcranial direct current stimulation (tDCS) targeting the right posterolateral cerebellum significantly improved language task accuracy and increased activation in brain areas associated with language processing, indicating its efficacy in enhancing cognitive functions.

In contrast, tDCS applied to the anterior sensorimotor cerebellum did not affect task performance, highlighting the distinct roles of different cerebellar regions in modulating both motor and cognitive tasks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Behavioral and Neural Effects of Regional Cerebellar tDCS. Rice, LC., D'Mello, AM., Stoodley, CJ.[2022]

In a study involving 70 participants, including 20 individuals with cerebellar degeneration, tDCS did not show any beneficial effects on motor adaptation during a reaching task, indicating that it may not be effective for alleviating motor impairments in these patients.

The lack of stimulation effects in both cerebellar patients and control groups suggests that tDCS may need further investigation with larger sample sizes and different parameters to determine its potential in neurorehabilitation for cerebellar disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebellar patients do not benefit from cerebellar or M1 transcranial direct current stimulation during force-field reaching adaptation. Hulst, T., John, L., Küper, M., et al.[2018]

References

1. England 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of targeted prefrontal cortex modulation with tDCS in patients with alcohol dependence. [2016]

3. Ireland pubmed.ncbi.nlm.nih.gov

Prefrontal cortex modulation using transcranial DC stimulation reduces alcohol craving: a double-blind, sham-controlled study. [2022]

4. Iran pubmed.ncbi.nlm.nih.gov

The Effect of Different Transcranial Direct Current Stimulation (tDCS) Protocols on Drug Craving and Cognitive Functions in Methamphetamine Addicts. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Multi-session electrical neuromodulation effects on craving, relapse and cognitive functions in cocaine use disorder: A randomized, sham-controlled tDCS study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

The clinical application of transcranial direct current stimulation in patients with cerebellar ataxia: a systematic review. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Cerebellar Transcranial Direct Current Stimulation in Children with Autism Spectrum Disorder: A Pilot Study on Efficacy, Feasibility, Safety, and Unexpected Outcomes in Tic Disorder and Epilepsy. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Cerebellar tDCS: how to do it. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Targeting the Human Cerebellum with Transcranial Direct Current Stimulation to Modulate Behavior: a Meta-Analysis. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

tDCS of the Cerebellum: Where Do We Stand in 2016? Technical Issues and Critical Review of the Literature. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Differential Behavioral and Neural Effects of Regional Cerebellar tDCS. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Cerebellar patients do not benefit from cerebellar or M1 transcranial direct current stimulation during force-field reaching adaptation. [2018]