Ultrasound Neuromodulation for Alcoholism

Overseen By Sierra Brandts, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Pregnant, Non-English, Psychosis, Suicidality, others

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

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Low-Intensity Focused Ultrasound (LIFU) affects brain activity in individuals with alcohol use disorder (AUD). The main goal is to determine if LIFU can alter brain patterns associated with alcohol cravings and use. Participants are divided into two groups, each receiving a specific type of LIFU treatment. The trial seeks individuals diagnosed with AUD who are willing to undergo brain imaging, such as an MRI. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could lead to new treatments for AUD.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators.

What prior data suggests that Low-Intensity Focused Ultrasound is safe for treating alcohol use disorder?

Research has shown that Low Intensity Focused Ultrasound (LIFU) is generally safe and easy for people to handle. In studies using LIFU on the brain, participants did not experience serious side effects. One study focused on individuals with substance use disorders and found the procedure safe, helping to reduce some symptoms. Another study tested LIFU at different energy levels and found participants tolerated it well.

These findings suggest that LIFU could be a promising new method to help treat conditions like alcohol use disorder, with no major safety concerns reported so far. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Low Intensity Focused Ultrasound (LIFU) for treating alcoholism because it offers a non-invasive approach to neuromodulation. Unlike traditional options like medication or behavioral therapy, LIFU targets specific brain regions involved in addiction through precise ultrasound waves, potentially reducing cravings and withdrawal symptoms. This method could offer a new pathway for treatment with fewer side effects and without the need for surgery or drugs.

What evidence suggests that Low-Intensity Focused Ultrasound is effective for alcohol use disorder?

Studies have shown that Low-Intensity Focused Ultrasound (LIFU) can safely alter brain activity without surgery. Research suggests that LIFU might help treat substance use disorders by targeting specific brain areas involved in addiction. In this trial, participants will receive either VS LIFU or VPL LIFU, which are different applications of LIFU. One study found that varying levels of LIFU could affect deep brain regions linked to behaviors and cravings. Specifically, early evidence in people with severe alcohol use disorder showed that ultrasound treatment might alter the brain in ways that reduce alcohol cravings. While more research is needed, LIFU offers a promising new approach for treating alcohol use disorder. ^{1 4 6 7 8}

Who Is on the Research Team?

Khaled Moussawi, MD, PhD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with alcohol use disorder, as defined by having at least two DSM-5 criteria in the past year. Participants must be willing to have a brain MRI and follow the study protocol. It's not for those with severe mental disorders, pregnant or breastfeeding women, people on other AUD trials, those with recent suicidality, non-English speakers, cognitive impairments, significant brain abnormalities or major medical conditions.

Inclusion Criteria

Documentation of an AUD diagnosis per DSM-5 criteria as evidenced by problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least two of the DSM-5 criteria, occurring within a 12-month period

Be willing to undergo a brain MRI and follow study protocol

Exclusion Criteria

Primary psychosis, Bipolar I, or severe personality disorder

Pregnant or breastfeeding

Presence of a condition or abnormality that would compromise the safety of the patient or the quality of the data

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Low-Intensity Focused Ultrasound (LIFU) treatment targeting the ventral striatum and ventral pallidum

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and reward network activity

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low Intensity Focused Ultrasound

Trial Overview The study is testing Low Intensity Focused Ultrasound (LIFU) to see how it affects brain activity in patients who struggle with excessive alcohol consumption. The goal is to determine if LIFU can help manage Alcohol Use Disorder (AUD).

How Is the Trial Designed?

Group I: VS LIFU/ VPL LIFU Experimental Treatment 1 Intervention

Participants will be assigned to receive VS LIFU during the first LIFU treatment session.

Group II: VPL LIFU/VS LIFU Active Control 1 Intervention

Participants will be assigned to receive VPL LIFU during the first LIFU treatment session.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Published Research Related to This Trial

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]

In a long-term study of 5 patients with treatment-resistant alcohol addiction, deep brain stimulation (DBS) of the nucleus accumbens resulted in complete absence of alcohol cravings for all participants, with 2 remaining abstinent for years and 3 significantly reducing their alcohol intake.

No severe or long-lasting side effects were reported, suggesting that DBS could be a safe and promising treatment option for severe alcohol addiction, although further research with larger clinical trials is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial. Müller, UJ., Sturm, V., Voges, J., et al.[2017]

Repetitive transcranial magnetic stimulation (rTMS) shows promise as a neuromodulation treatment for alcohol use disorder (AUD), particularly by targeting the salience network in the brain, which is linked to addiction and relapse.

Stimulation of specific brain areas, such as the anterior insula and dorsal anterior cingulate cortex, may enhance the effectiveness of rTMS in reducing relapse rates in individuals with AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. Padula, CB., Tenekedjieva, LT., McCalley, DM., et al.[2022]

Low Intensity Focused Ultrasound (LIFU) targeting the nucleus accumbens was found to be safe and well-tolerated in a pilot study with four participants undergoing treatment for opioid use disorder, showing no adverse structural changes in MRI scans.

Participants receiving the higher dose of LIFU (90 W) experienced significant reductions in craving for their primary substances, with effects lasting up to 90 days post-treatment, indicating potential for LIFU as a novel intervention for substance use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity focused ultrasound targeting the nucleus accumbens as a potential treatment for substance use disorder: safety and feasibility clinical trial. Mahoney, JJ., Haut, MW., Carpenter, J., et al.[2023]

A systematic review of 26 randomized sham-controlled trials suggests that non-invasive brain stimulation (NIBS) may effectively reduce cravings and improve cognitive functions in patients with alcohol and tobacco use disorders.

NIBS shows promise as a new treatment approach for substance use disorders, indicating its potential therapeutic effects in managing addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of Non-Invasive Brain Stimulation in Substance Use Disorders: A Review of Randomized Sham-Controlled Clinical Trials. Trojak, B., Sauvaget, A., Fecteau, S., et al.[2018]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAc) in six patients with severe alcohol use disorder (AUD) led to significant reductions in cravings, alcohol consumption, and alcohol-related compulsivity over 12 months, demonstrating its potential as a safe and effective treatment.

Improvements in compulsive drinking behaviors were linked to reduced glucose metabolism in the NAc and decreased functional connectivity between the NAc and the visual association cortex, suggesting a mechanism by which NAc-DBS may help mitigate the effects of alcohol-related cues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the nucleus accumbens in the treatment of severe alcohol use disorder: a phase I pilot trial. Davidson, B., Giacobbe, P., George, TP., et al.[2023]

In a clinical trial with 50 individuals suffering from alcohol use disorder (AUD), continuous theta burst stimulation (TBS) to the medial prefrontal cortex significantly reduced drinking behavior and brain reactivity to alcohol cues for up to 3 months after treatment.

Participants receiving real TBS were 2.71 times more likely to stay in the study and 3.09 times more likely to remain sober compared to those receiving sham treatment, indicating the potential efficacy of TBS as a therapeutic intervention for AUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medial Prefrontal Cortex Theta Burst Stimulation Improves Treatment Outcomes in Alcohol Use Disorder: A Double-Blind, Sham-Controlled Neuroimaging Study. McCalley, DM., Kaur, N., Wolf, JP., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11612502/

The therapeutic potential of low-intensity focused ultrasound ... LIFU is a promising modality for precise and invasive modulation of brain activity, capable of redefining the landscape of SUD treatment.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07099950

Dose-Dependent Effects of Low-Intensity Focused ... Low-intensity focused ultrasound (LIFU) has emerged as a tool to modulate the activity of deep brain structures noninvasively and reversibly, ...

3. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2023.1211566/full

Low-intensity focused ultrasound targeting the nucleus ... This study evaluated two doses (60 and 90 W) of Low Intensity Focused Ultrasound (LIFU), targeting the bilateral nucleus accumbens (NAc), in individuals with ...

4. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06518785

Ultrasound Neuromodulation of the Brain for Alcohol Use ... This study aims to examine the effects of Low-Intensity Focused Ultrasound (LIFU) on brain activity in patients with alcohol use disorder.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2214751925000611

Sub-ablative thermo-stimulation with high-intensity focused ... This study presents the outcomes of two male patients, aged 42 and 47 years, diagnosed with severe AUD who underwent magnetic resonance-guided focused ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871623001941

First in the World Trial of low Intensity Focused Ultrasound ... This is the first investigation of LIFU targeting the NAc in individuals with SUD. The procedure was safe and well-tolerated, LIFU acutely reduced cue-induced ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05467085

Imaging-Guided Low Intensity Focused Ultrasound (LIFU) This research study is to investigate the safety, feasibility, and possible therapeutic benefits of a technology called Low Intensity Focused Ultrasound ...

8. researchstudies.cuanschutz.edu researchstudies.cuanschutz.edu/Study/25-0695

Find a Research Study This research study plans to learn more about how a form of brain stimulation called low-intensity focused ultrasound (LIFU) affects the brain and behaviors ...