rTMS for Mild Cognitive Impairment and Alcoholism

Not currently recruiting at 1 trial location

Overseen By Rhia Walton, M.A.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Medical University of South Carolina

Must not be taking: Anticholinergics, Sedatives

Disqualifiers: Dementia, Bipolar, Schizophrenia, 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: 8

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called repetitive transcranial magnetic stimulation (rTMS), which uses magnetic fields to improve brain function. The goal is to determine if rTMS can help individuals with mild cognitive impairment and alcohol use disorder by reducing heavy drinking and enhancing memory and thinking. This treatment could benefit those who drink heavily (at least 4 drinks for women and 5 for men on 4 or more days a week) and experience memory or thinking issues. Participants will undergo rTMS sessions over one week and be monitored for changes in drinking habits and cognitive function. The study seeks individuals aged 60-85 who speak English and have been diagnosed with alcohol use disorder and mild cognitive impairment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative treatment.

Will I have to stop taking my current medications?

The trial requires that you stop using daily or weekly anticholinergic or sedative medications. However, you can continue taking cholinesterase inhibitors, NMDA receptor antagonists, and antidepressants if you have been on a stable dose for at least 4 weeks before joining the trial.

What prior data suggests that rTMS is safe for treating mild cognitive impairment and alcoholism?

Research has shown that repetitive transcranial magnetic stimulation (rTMS), particularly intermittent theta burst stimulation (iTBS), is generally safe. Studies have found that rTMS can improve thinking skills in individuals with mild memory problems and Alzheimer's-related conditions. It has also reduced heavy drinking in those with alcohol use disorder.

Previous research indicates that rTMS is a non-invasive and painless treatment, not involving surgery or needles. Most people tolerate it well. Some may experience mild side effects like headaches or scalp discomfort, but these typically resolve on their own. Although this trial is in the early stages with limited safety data from this specific study, existing research suggests that rTMS is safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for mild cognitive impairment and alcoholism, which often involve medication and lifestyle changes, this investigational treatment uses intermittent Theta Burst Stimulation (iTBS) as a form of repetitive Transcranial Magnetic Stimulation (rTMS). This method is non-invasive and targets specific brain networks by delivering magnetic pulses, potentially offering a more direct approach to altering brain activity. Researchers are excited because this technique could lead to faster and more personalized treatment outcomes, with brain imaging helping to fine-tune the stimulation to each individual's neural patterns.

What evidence suggests that rTMS is effective for mild cognitive impairment and alcoholism?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can enhance thinking and memory in people with mild cognitive impairment (MCI). Studies have found that rTMS boosts brain function in those with Alzheimer's disease and similar conditions. It also reduces heavy drinking in people with alcohol use disorder. In this trial, participants will receive the Active, Open Label iTBS-rTMS treatment, which uses magnetic fields to stimulate brain cells, potentially addressing both memory problems and alcohol misuse simultaneously. Early research suggests that rTMS is safe and could be effective in these areas. ^{1 3 4 6 7}

Who Is on the Research Team?

Lisa McTeague, PhD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for older adults aged 60-85 who have mild cognitive impairment (MCI) and struggle with alcohol use disorder. They must be heavy drinkers, as defined by specific amounts per week, speak English fluently, and have good vision and hearing to participate in assessments. Pregnant individuals are excluded.

Inclusion Criteria

I have had 4 or more heavy drinking days each week in the last month.

English as a first/primary language

I am between 60 and 85 years old.

Exclusion Criteria

Current substance use disorder other than AUD or nicotine use disorder, bipolar disorder, or schizophrenia spectrum or other psychotic disorder

I have been diagnosed with dementia or a major thinking/memory disorder.

I use certain daily medications, but my treatment plan has been stable for the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive 10 sessions of iTBS-rTMS per day, 5 days per week for one week (50 sessions total)

1 week

5 visits (in-person)

Post-treatment Assessment

Clinical assessments and brain MRI at 1-week post-treatment, with weekly online self-report assessments up to four weeks

4 weeks

1 visit (in-person), weekly online assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Active, Open Label iTBS-rTMS

Trial Overview The study tests a treatment called iTBS-rTMS which is an active form of brain stimulation therapy. It's open label, meaning everyone knows they're getting the real treatment. The goal is to see if it can help reduce heavy drinking while also improving memory and thinking skills in older adults.

How Is the Trial Designed?

Group I: Active, Open Label iTBS-rTMS Experimental Treatment 1 Intervention

Individuals will receive 10 sessions of iTBS-rTMS per day, 5 days per week for one week (50 sessions total). All will undergo clinical assessments and brain MRI at pre-treatment and at 1-week post-treatment, and clinical assessments at 4-weeks post-treatment. Weekly post-treatment online self-report assessments will be collected up to four weeks. Resting-state parcellations of pre- and post-fMRI will be completed for personalized targeting and network parcellations.

Active, Open Label iTBS-rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Treatment-resistant depression
• Obsessive-compulsive disorder (OCD)
• Migraines
• Anxiety with depression
• Smoking dependence
• Bipolar depression
• Depression in adolescents 15 years and older

Approved in United States as Deep TMS for:

• Obsessive-compulsive disorder (OCD)
• Smoking cessation
• Major depressive disorder (MDD)

Approved in European Union as Deep TMS for:

• Obsessive-compulsive disorder (OCD)
• Smoking cessation
• Major depressive disorder (MDD)
• Additional mental health and neurological conditions

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Published Research Related to This Trial

Repetitive magnetic stimulation (rTMS) is a non-invasive and painless technique that can effectively activate specific areas of the brain, making it useful for studying language, memory, and visual perception.

rTMS shows potential therapeutic benefits for conditions like movement disorders and depression, but there are safety considerations regarding its potential to induce seizures, which are addressed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. Brandt, SA., Ploner, CJ., Meyer, BU.[2019]

In a chronic alcoholic patient with slight brain atrophy, transcranial magnetic stimulation (TMS) revealed an increased resting threshold and a dominance of D waves, indicating direct stimulation of corticospinal neurons, while I waves were unclear or absent.

The absence of clear I waves suggests impairment in the interneuronal circuitry due to brain damage from chronic alcohol abuse, highlighting how alcohol can affect motor pathways in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Direct recording of the output of the motor cortex produced by transcranial magnetic stimulation in a patient with cerebral cortex atrophy. Di Lazzaro, V., Oliviero, A., Pilato, F., et al.[2019]

In a study involving 19 alcohol-dependent patients, higher baseline activation of the dorsal anterior cingulate cortex (dACC) was associated with a lower likelihood of relapse after treatment, suggesting it may act as a protective factor against relapse.

Accelerated high-frequency rTMS treatment increased dACC activation in patients with lower baseline levels, indicating that this intervention can modify brain activity related to relapse risk, although 68% of participants relapsed within 4 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated HF-rTMS Protocol has a Rate-Dependent Effect on dACC Activation in Alcohol-Dependent Patients: An Open-Label Feasibility Study. Herremans, SC., De Raedt, R., Van Schuerbeek, P., et al.[2016]

Excitatory repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral pre-frontal cortex significantly reduces craving for substances in patients with dependence, with a strong effect size (Hedges' g = -0.62) based on a meta-analysis of 26 randomized controlled trials involving 748 participants.

In addition to reducing cravings, rTMS also effectively decreases substance consumption, particularly when using excitatory stimulation protocols, indicating its potential as a therapeutic intervention for substance dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: a systematic review and meta-analysis. Zhang, JJQ., Fong, KNK., Ouyang, RG., et al.[2020]

In a study involving 60 male inpatients with alcohol dependence, repetitive transcranial magnetic stimulation (rTMS) was administered over ten daily sessions, targeting the left dorsolateral prefrontal cortex (DLPFC).

The results showed no significant reduction in alcohol craving scores immediately after treatment or two weeks later, indicating that rTMS may not be effective for reducing cravings in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A sham-controlled trial of repetitive transcranial magnetic stimulation over left dorsolateral prefrontal cortex and its effects on craving in patients with alcohol dependence. Raikwar, S., Divinakumar, KJ., Prakash, J., et al.[2022]

In healthy individuals, acute ethanol intake significantly enhances cortical excitability, as evidenced by increased motor evoked potential (MEP) size and longer cortical silent period (CSP) duration after 5Hz rTMS.

In contrast, patients with chronic alcohol consumption showed impaired MEP facilitation after rTMS, indicating that chronic ethanol use alters cortical plasticity and excitability, while still allowing for CSP lengthening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute and chronic effects of ethanol on cortical excitability. Conte, A., Attilia, ML., Gilio, F., et al.[2018]

In a pilot study involving 14 patients with alcohol use disorder (AUD), deep repetitive Transcranial Magnetic Stimulation (rTMS) of the dorsolateral prefrontal cortex led to a significant reduction in dopamine transporter (DAT) availability and alcohol intake after four weeks of treatment.

The results suggest that rTMS may modulate dopaminergic activity, indicating its potential efficacy as a therapeutic intervention for reducing alcohol consumption in AUD patients, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Transcranial Magnetic Stimulation of the Dorsolateral Prefrontal Cortex in Alcohol Use Disorder Patients: Effects on Dopamine Transporter Availability and Alcohol Intake. Addolorato, G., Antonelli, M., Cocciolillo, F., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) is emerging as a promising and safe treatment for alcohol use disorders (AUDs), potentially addressing the limited therapeutic options currently available.

rTMS may work by altering neurocircuitries related to alcohol addiction, with evidence from visual imaging studies and clinical pilot studies showing its effects on reducing alcohol craving and intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation: Re-wiring the alcoholic human brain. Diana, M., Bolloni, C., Antonelli, M., et al.[2020]

High-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the right dorsolateral pre-frontal cortex significantly reduced alcohol craving in 45 patients with alcohol dependence, demonstrating its potential as an effective treatment strategy.

The study showed a moderate effect size for the anticraving effects of rTMS, suggesting that it could be combined with other medications to further reduce cravings and prevent relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of repetitive transcranial magnetic stimulation in alcohol dependence: a sham-controlled study. Mishra, BR., Nizamie, SH., Das, B., et al.[2022]

High-frequency repetitive transcranial magnetic stimulation (rTMS) at 10 Hz for 14 days significantly improved attention bias towards alcohol-related cues and reduced impulsivity in male patients with alcohol use disorder (AUD) after acute withdrawal, as evidenced by shorter response times in cognitive tasks.

Patients receiving rTMS also showed significant improvements in cognitive function, with increased scores on the Montreal Cognitive Assessment (MoCA) and decreased scores on the Barratt Impulsiveness Scale (BIS-II), indicating enhanced cognitive abilities and reduced impulsiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of High-Frequency Repetitive Transcranial Magnetic Stimulation on Visual Selective Attention in Male Patients With Alcohol Use Disorder After the Acute Withdrawal. Feng, Z., Wu, Q., Wu, L., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05896332

NCT05896332 | rTMS in Older Adults With MCI and AUD Interventional Model Description: We propose to conduct an open-label Phase I trial of accelerated iTBS-rTMS for AUD+MCI. We propose to recruit 35 treatment- ...

2. withpower.com withpower.com/trial/phase-1-alcoholism-6-2023-9c859

rTMS for Mild Cognitive Impairment and Alcoholism Repetitive transcranial magnetic stimulation (rTMS) has been shown to improve cognition in Alzheimer's Disease and Related Dimentias (ADRD) and separately ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10573645/

Repetitive Transcranial Magnetic Stimulation (rTMS) in Mild ... The results of the reviewed studies suggested that rTMS in MCI patients is safe and effective for enhancing cognitive functions, thus making it a potential ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05327257

NCT05327257 | iTBS rTMS in Mild Cognitive Impairment The purposes of this research are to test whether it is feasible to administer a treatment protocol called intermittent theta burst stimulation (iTBS) ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1041610225002431

Efficacy and safety of transcranial magnetic stimulation on ... The reviewed studies provide favorable evidence of improved cognition with TMS across all groups with cognitive impairment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11306417/

Efficacy and Safety of Transcranial Magnetic Stimulation on ... We aim to analyze the efficacy and safety of TMS on cognition in mild cognitive impairment (MCI), Alzheimer disease (AD), AD-related dementias, and nondementia ...

7. jnnp.bmj.com jnnp.bmj.com/content/95/11/1036

A phase I trial of accelerated intermittent theta burst rTMS for ... Background Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI).