Focused Ultrasound for Tobacco Use Disorder

(LIFU_TUD Trial)

Recruiting at 1 trial location

Overseen By Evan Lindeman, BS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington D.C. Veterans Affairs Medical Center

Must not be taking: Psychotropics, Antibiotics, Antihistamines, others

Disqualifiers: Head injury, Seizures, Neurologic disorders, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 session each for LIFU and sham

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist individuals with tobacco use disorder who struggle with cravings triggered by smoking cues. It employs low intensity focused ultrasound, a form of non-invasive brain stimulation, to target a brain area potentially involved in these cravings. The trial compares this treatment to a placebo to determine its effectiveness in reducing cravings and its safety. Individuals who smoke more than 10 cigarettes a day and are considering quitting might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could lead to new treatments for tobacco use disorder.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any psychotropic medications (like antidepressants, anxiolytics, and antipsychotics) and any other medications that can affect brain activity, such as certain antibiotics, antihistamines, or muscle relaxants.

What prior data suggests that this technique is safe for individuals with tobacco use disorder?

Research shows that Low Intensity Focused Ultrasound (LIFU) is a non-invasive method used to target specific brain areas. Previous studies have explored LIFU's potential to reduce cravings, particularly in individuals aiming to quit smoking. While scientists continue to study its safety, LIFU is generally considered safe and well-tolerated. As a non-invasive technique, it does not involve surgery or entering the body, typically resulting in fewer side effects.

Some research suggests that individuals with damage to the brain area targeted by LIFU, known as the insula, may find it easier to quit smoking without cravings or relapses. This indicates that targeting the insula with LIFU could help reduce smoking cravings. Although specific side effects of LIFU for smoking are not detailed, its non-invasive nature suggests it is generally safe.

Participants in clinical trials typically undergo thorough check-ups to monitor any possible side effects. Consulting a healthcare professional about joining a clinical trial is advisable to understand the benefits and risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional methods for treating Tobacco Use Disorder, which often include nicotine replacement therapies and medications like varenicline or bupropion, Low Intensity Focused Ultrasound (LIFU) is unique because it uses sound waves to target specific areas of the brain associated with addiction. This non-invasive technique offers a new way to potentially modify brain activity without the need for pharmaceuticals, reducing the risk of side effects. Researchers are excited about LIFU because it holds the promise of providing a safer, quicker intervention that could help people quit smoking more effectively than current options.

What evidence suggests that low intensity focused ultrasound is effective for tobacco use disorder?

Research has shown that low-intensity focused ultrasound (LIFU) can help treat tobacco addiction by targeting specific brain areas related to cravings. This trial will investigate the effects of LIFU, with participants receiving either LIFU or a sham treatment in a double-blind, crossover design. Studies indicate that LIFU can reach deep parts of the brain, such as the dorsal anterior insula (dAI), which plays a key role in controlling cravings. Early results suggest that using LIFU to influence the dAI can reduce cravings triggered by smoking cues. This noninvasive method, which does not involve surgery, offers a promising option for those wanting to quit smoking. Although more research is needed, the potential for LIFU to help with nicotine addiction is encouraging. ^{1 2 4 6 7}

Who Is on the Research Team?

Mary R Lee, MD

Principal Investigator

Veterans Affairs Medical Center, Washington DC

Are You a Good Fit for This Trial?

This trial is for individuals with Tobacco Use Disorder who want to explore a new treatment. Participants must be able to undergo MRI scans and neurological assessments. The study excludes those with certain medical conditions or metal implants that could interfere with MRI, pregnant women, and people unable to give informed consent.

Inclusion Criteria

I am a veteran between 18 and 65 years old.

Meet the DSM-5 criteria for current Tobacco Use Disorder (moderate to severe) as diagnosed by the Structured Clinical Interview for DSM-5

I currently smoke more than 10 cigarettes daily without quitting for more than 3 months in the past year.

Exclusion Criteria

Not under current treatment for smoking cessation

Ferromagnetic implants or other contraindications for MRI

I have no history of major brain or neurological conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LIFU and sham stimulation to assess the effects on dAI BOLD activity and craving in response to smoking cues

1 session each for LIFU and sham

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 hour post each session

What Are the Treatments Tested in This Trial?

Interventions

• Low Intensity Focused Ultrasound

Trial Overview

The trial tests if low intensity focused ultrasound (LIFU) can reduce cravings in smokers by targeting a brain area called the dorsal anterior insula. It compares LIFU's effects on brain activity and craving responses against sham (fake) treatments using functional magnetic resonance imaging (fMRI).

How Is the Trial Designed?

Group I: Sham/LIFU Experimental Treatment 1 Intervention

double-blind, sham-controlled, crossover study in N=44 individuals with Tobacco Use Disorder

Group II: LIFU/Sham Experimental Treatment 1 Intervention

double-blind, sham-controlled, crossover study in N=44 individuals with Tobacco Use Disorder

Who Is Running the Clinical Trial?

Washington D.C. Veterans Affairs Medical Center

Lead Sponsor

Trials

45

Recruited

18,500+

Published Research Related to This Trial

Non-invasive brain stimulation (NIBS) methods, particularly repetitive transcranial magnetic stimulation (rTMS), have shown a significant increase in sustained smoking abstinence rates, with a risk ratio of 2.39 compared to sham treatments, based on a meta-analysis of 7 studies involving 699 participants.

The effectiveness of NIBS was even greater when targeting specific brain areas, such as the left dorsolateral prefrontal cortex, with a risk ratio of 4.34, indicating that certain stimulation techniques may enhance the likelihood of long-term smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive brain stimulation for smoking cessation: a systematic review and meta-analysis. Petit, B., Dornier, A., Meille, V., et al.[2023]

Chronic smokers exhibit significant changes in brain activity during resting state, with increased activity in areas related to addiction and decreased activity in regions associated with memory and smoking sensations, as shown by fMRI in a study of 20 smokers and 19 nonsmokers.

The study found that both the amount of nicotine consumed and the severity of nicotine dependence correlate with these changes in brain activity, indicating a neurobiological mechanism underlying smoking addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spontaneous brain activity in chronic smokers revealed by fractional amplitude of low frequency fluctuation analysis: a resting state functional magnetic resonance imaging study. Chu, S., Xiao, D., Wang, S., et al.[2014]

Nicotine positively affects attention and mood by altering regional cerebral blood flow (rCBF) in specific brain areas, such as decreasing activity in the anterior cingulate cortex and cerebellum while increasing it in the occipital cortex.

These effects were consistent in both smokers and non-smokers, suggesting that nicotine's impact on cognitive function is related to its influence on brain activity, which may explain the cognitive impairments and irritability experienced during nicotine withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral effects of nicotine during cognition in smokers and non-smokers. Ghatan, PH., Ingvar, M., Eriksson, L., et al.[2022]

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]

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]

Nicotine intake positively affects cortical excitability and plasticity in deprived smokers, but this effect is reversed in non-smokers, indicating that smoking status influences how nicotine impacts brain activity.

Non-invasive brain stimulation (NIBS) shows promise as a potential intervention for smoking cessation, suggesting that modifying cortical excitability could help change smoking behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The two-way relationship between nicotine and cortical activity: a systematic review of neurobiological and treatment aspects. de Miquel, C., Pross, B., Papazova, I., et al.[2022]

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]

Cigarette smoking is the leading preventable cause of death globally, with nearly 4 million deaths each year, highlighting the urgent need for effective smoking cessation treatments.

Current smoking cessation medications often fail for many smokers, prompting research into new treatments targeting various neurotransmitter systems involved in nicotine dependence, which could help those who struggle to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current pharmacological treatments for nicotine dependence. George, TP., O'Malley, SS.[2015]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06405074

Low Intensity Focused Ultrasound for Tobacco Use ...

The goal of this clinical trial is to to inhibit the dorsal anterior insula (dAI) with low intensity focused ultrasound (LIFU) to determine the causal role ...

2.

brainstimjrnl.com

brainstimjrnl.com/article/S1935-861X(24)01229-4/fulltext

Preliminary Results for Low Intensity Focused Ultrasound for ...

We present preliminary results from an ongoing study, using LIFU to modulate the AI to determine its causal role in smoking cue-induced craving.

3.

reporter.nih.gov

reporter.nih.gov/project-details/11070401

Low Intensity Focused Ultrasound for Tobacco Use Disorder

Low-intensity focused ultrasound (LIFU) is a noninvasive method to inhibit cortical and deep brain regions. LIFU can reach deep brain regions and has spatial ...

4.

withpower.com

withpower.com/trial/phase-tobacco-use-disorder-3-2022-cf0ab

Focused Ultrasound for Tobacco Use Disorder

Research suggests that non-invasive brain stimulation (NIBS), which includes techniques like LIFU, shows promise in treating tobacco use disorder by reducing ...

5.

brainstimjrnl.com

brainstimjrnl.com/article/S1935-861X(24)01229-4/pdf

High Resolution Targeting of the Human Insula

The functional role of the insula in nicotine addiction can be probed using low intensity focused ultrasound (LIFU). We present preliminary results from an ...

6.

trialx.com

trialx.com/clinical-trials/listings/290918/low-intensity-focused-ultrasound-for-tobacco-use-disorder-high-resolution-targeting-of-the-human-insula/?&geo_lat=38.8842&geo_lng=-77.1718&radius=10&place=Falls%20Church&user_country=United%20States

Low Intensity Focused Ultrasound for Tobacco Use Disorder

The main question[s] it aims to answer are: the safety and tolerability of dAI LIFU compared to sham stimulation in individuals with TUD; the ...

7.

fusfoundation.org

fusfoundation.org/posts/focused-ultrasound-neuromodulation-for-addiction-and-pain-three-clinical-trials-offered-for-veterans/

Focused Ultrasound Neuromodulation for Addiction and Pain

The research studies are testing low-intensity focused ultrasound neuromodulation for treating tobacco use disorder, opiate use disorder, and ...