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

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.

Is ultrasound neuromodulation safe for humans?

Research on Low Intensity Focused Ultrasound (LIFU) for substance use disorders suggests it is generally safe, as studies have not reported severe or long-lasting side effects. However, more research is needed to confirm its safety across different conditions. ^{1 2 3 4 5}

How is Low Intensity Focused Ultrasound (LIFU) different from other treatments for alcohol use disorder?

Low Intensity Focused Ultrasound (LIFU) is unique because it uses sound waves to non-invasively target specific brain areas, like the nucleus accumbens, which is involved in addiction. Unlike traditional treatments that may involve medication or invasive procedures, LIFU offers a novel approach by potentially reducing cravings and improving brain function without surgery or drugs. ^{1 2 4 5 6}

What data supports the effectiveness of the treatment Low Intensity Focused Ultrasound (LIFU) for alcoholism?

Research on similar treatments, like deep brain stimulation (DBS) targeting the nucleus accumbens, shows promise in reducing alcohol cravings and consumption. This suggests that targeting the same brain area with LIFU might also help with alcohol addiction. ^{2 3 5 6 7}

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

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]

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]

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]

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]

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]

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]

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. England 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. [2023]

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

Neuromodulation Therapies for Alcohol Addiction: A Literature Review. [2022]

3. Switzerland 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. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Targeting the Salience Network: A Mini-Review on a Novel Neuromodulation Approach for Treating Alcohol Use Disorder. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Nucleus Accumbens Deep Brain Stimulation for Alcohol Addiction - Safety and Clinical Long-term Results of a Pilot Trial. [2017]

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

Outcome of Non-Invasive Brain Stimulation in Substance Use Disorders: A Review of Randomized Sham-Controlled Clinical Trials. [2018]

7. United States 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. [2023]