LIFU for Cocaine Use Disorder

Overseen By Tracie Kostelac

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Virginia

Disqualifiers: Contact study coordinator for details

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

Compensation: Varies

Number of Visits: 7

Duration: 8 weeks

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 cravings in individuals with Cocaine Use Disorder. Researchers aim to determine if this non-invasive treatment is safe and alters brain activity associated with cravings when exposed to cocaine cues. The study includes both real LIFU treatment and a placebo (inactive version) to compare effects. Individuals who have struggled with cocaine use in the past six months and can undergo imaging tests might be suitable candidates.

As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatments for cocaine addiction.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications.

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 contact the study coordinator for more details.

What prior data suggests that Low-Intensity Focused Ultrasound is safe for individuals with Cocaine Use Disorder?

Research has shown that Low-Intensity Focused Ultrasound (LIFU) is generally safe. Studies have found that LIFU can alter brain activity without surgery, targeting small areas in the brain through the skull. Current research indicates that LIFU is safe and is undergoing clinical trials to further explore its effects. Although exact numbers on side effects are not available, existing evidence suggests that LIFU is well-tolerated. Prospective participants can be reassured by its safety record to date. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Low-Intensity Focused Ultrasound (LIFU) for treating cocaine use disorder because it offers a new non-invasive approach that differs significantly from existing treatments like behavioral therapy and medication-assisted options such as disulfiram or naltrexone. Unlike these standard treatments, LIFU uses precise sound waves to target and modulate brain activity, potentially reducing cravings and improving self-control. This technique is promising because it could provide faster, more targeted effects without the need for medication, which often comes with unwanted side effects.

What evidence suggests that Low-Intensity Focused Ultrasound is effective for Cocaine Use Disorder?

Research has shown that Low-Intensity Focused Ultrasound (LIFU) offers a promising method to influence brain activity without surgery. In this trial, participants will receive both LIFU and a Sham LIFU device in a randomized order to target brain areas involved in addiction, aiming to reduce cravings in individuals with Cocaine Use Disorder (CUD). Studies have found that LIFU can safely and effectively alter activity in deep brain regions, potentially reducing cravings. While further research is necessary, LIFU has demonstrated potential in affecting brain regions linked to craving and addiction, offering new hope for those with CUD. ^{1 3 5 6 7}

Who Is on the Research Team?

Nassima Ait-Daoud Tiouririne, MD

Principal Investigator

University of Virginia, Center for Leading Edge Addiction Research

Are You a Good Fit for This Trial?

This trial is for adults over 18 with a recent diagnosis of cocaine use disorder, who can lie still for imaging tests, have reliable transport, and stable housing. They must be able to avoid cocaine at certain times during the study and meet criteria for MRI scans.

Inclusion Criteria

I can lie down for a long time for scans.

I am willing and able to follow the study's schedule and procedures.

Will have a stable residence during the 2 weeks prior to randomization and not be at risk of losing housing in next 2 months

Exclusion Criteria

Please contact PI or Study Coordinator for more details.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive LIFU and sham interventions in a randomized order

8 weeks

5 visits (in-person), 2 phone calls

Follow-up

Participants return one month after the second session for an in-person follow-up to assess safety and effectiveness

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Low-Intensity Focused Ultrasound
• Sham LIFU device

Trial Overview The study is testing Low-Intensity Focused Ultrasound (LIFU) against a sham device to see if it reduces cravings in people with Cocaine Use Disorder by looking at brain activity and subjective craving levels after exposure to cocaine cues.

How Is the Trial Designed?

Group I: Low-Intensity Focused Ultrasound (LIFU) Experimental Treatment 1 Intervention

All subjects to receive LIFU and Sham in a randomized order.

Group II: Sham LIFU Placebo Group 1 Intervention

All subjects to receive LIFU and Sham in a randomized order.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

In a randomized controlled trial involving 122 participants, disulfiram combined with psychotherapy significantly improved treatment retention and increased the duration of abstinence from both alcohol and cocaine.

Cognitive Behavioral Therapy (CBT) and Twelve Step Facilitation (TSF) were more effective in reducing cocaine use compared to supportive psychotherapy, highlighting the importance of combining medication with targeted therapies for individuals with co-occurring substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of cocaine and alcohol dependence with psychotherapy and disulfiram. Carroll, KM., Nich, C., Ball, SA., et al.[2019]

Cocaine abuse, particularly prevalent in North America since the 1980s, leads to significant health issues due to its rapid absorption and intense stimulation of the brain's reward systems, primarily through its effects on dopamine.

While cocaine has some therapeutic uses as a local anesthetic, its abuse can cause severe medical complications, including sudden death from central nervous system overstimulation and vasoconstriction, highlighting the urgent need for effective treatment strategies beyond current psychosocial approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pharmacology and toxicology of cocaine. Benowitz, NL.[2019]

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 9 studies involving 1747 participants found no significant evidence supporting the efficacy of acupuncture in treating cocaine addiction, with a pooled odds ratio of 0.76 indicating no clear benefit over control.

The trials faced significant participant dropout rates, averaging 50%, which may have weakened the reliability of the findings and suggests that further research is needed to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of acupuncture for cocaine dependence: a systematic review & meta-analysis. Mills, EJ., Wu, P., Gagnier, J., et al.[2019]

This pilot randomized controlled trial will evaluate the feasibility and preliminary efficacy of Memory-focused Cognitive Therapy (MFCT) for treating cocaine use disorder (CUD) in 30 adults over 15 weeks, aiming to modify cocaine-related memories to reduce cravings.

Participants will be compared on their craving levels and abstinence rates after receiving MFCT alongside standard care, with results expected to inform future larger studies on this novel intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory-focused cognitive therapy for cocaine use disorder: Rationale, design and protocol for an external pilot randomised controlled trial. Marsden, J., Goetz, C., Meynen, T., et al.[2022]

Chronic cocaine use can lead to severe midfacial injuries, requiring careful surgical intervention to restore nasal and palatal function, as demonstrated in a series of 4 patients, with 3 undergoing successful reconstruction after an 18-month drug-free period.

Acute cocaine-induced lesions should be treated with aggressive debridement, and careful monitoring is essential for patients to prevent further complications and ensure proper healing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive surgical management of cocaine-induced midline destructive lesions. Colletti, G., Autelitano, L., Chiapasco, M., et al.[2022]

A survey of 332 regular cocaine users in São Paulo revealed that adverse reactions to cocaine are very common, with symptoms like hot flushes (84%), uncontrollable shaking (76%), and feeling ill (75%) being frequently reported.

The study found that more severe adverse reactions, such as convulsions (18%) and passing out (21%), were linked to factors like higher dependence on cocaine and the use of tranquilizers, highlighting the need for preventive strategies to mitigate these potentially fatal effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with adverse reactions to cocaine among a sample of long-term, high-dose users in São Paulo, Brazil. Ferri, CP., Dunn, J., Gossop, M., et al.[2019]

This paper presents the first reported case of sudden bilateral sensorineural hearing loss following intravenous cocaine use, highlighting a potential link between cocaine abuse and inner ear damage.

The authors emphasize the need for further research to explore the mechanisms by which cocaine affects inner ear cells and their metabolism, as current data on this topic is very limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Considerations on the physiopathological mechanism of inner ear damage induced by intravenous cocaine abuse: cues from a case report. Ciorba, A., Bovo, R., Prosser, S., et al.[2013]

Neurostimulation techniques, especially transcranial magnetic stimulation and transcranial direct current stimulation, have shown promise in safely reducing cocaine cravings, although studies are limited in number and sample size.

Deep brain stimulation has shown some positive results in a single patient, but more research is needed to determine its overall efficacy and safety for treating cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurostimulation techniques in the treatment of cocaine dependence: A review of the literature. Rachid, F.[2018]

In a study involving primarily young, indigent African-American crack cocaine users, adjunct therapies like acupuncture, anticraving medication, and brainwave therapy were tested to improve retention in intensive outpatient treatment, but none showed a direct impact on drug use outcomes.

However, higher dosages of any adjunct therapy were linked to increased days in treatment and more standard treatment sessions attended, which correlated with negative drug test results at follow-up, suggesting that while the adjunct therapies didn't directly reduce drug use, they may help keep patients engaged in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of adjunct therapies in crack cocaine treatment. Richard, AJ., Montoya, ID., Nelson, R., et al.[2022]

Nalmefene is the first medication approved for reducing alcohol consumption in heavy drinking alcohol-dependent patients, providing an alternative treatment option for those who may not be ready to pursue complete abstinence.

While nalmefene shows promise in changing the treatment approach for alcohol use disorder (AUD), further research is needed on its safety in special populations and its effectiveness compared to other medications for alcohol reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of nalmefene for the treatment of alcohol use disorder: an update. López-Pelayo, H., Zuluaga, P., Caballeria, E., et al.[2020]

In a study involving 30 cocaine-dependent patients, auricular acupuncture did not show significant differences in reducing psychological and physiological cravings for cocaine compared to a sham acupuncture group.

Both groups experienced changes in psychological craving from pretest to posttest, but the acupuncture intervention did not provide any additional benefits over the placebo treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of auricular acupuncture on psychophysiological measures of cocaine craving. Killeen, TK., Haight, B., Brady, K., et al.[2004]

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. reporter.nih.gov reporter.nih.gov/search/13E1CC034E8BC0D07598B8961CAA4A01A2FFCEB861BF/project-details/10465480

Low-intensity focused ultrasound for cocaine use disorder This project will examine how ultrasound directed to a small but critical brain region implicated in CUD can affect brain activity to reduce craving for cocaine ...

3. trialx.com trialx.com/clinical-trials/listings/266705/low-intensity-focused-ultrasound-for-cocaine-use-disorder/

Low-Intensity Focused Ultrasound for Cocaine Use Disorder This study aims to understand the role of Low-Intensity Focused Ultrasound on craving levels for cocaine as evidenced by diagnostic imaging of ...

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

Low-intensity focused ultrasound targeting the nucleus ... Outcomes were the safety, tolerability, and feasibility during the LIFU procedure and throughout the 90-day follow-up. Outcomes also included ...

5. 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, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05997030

Low-Intensity Focused Ultrasound (LIFU) Neuromodulation These trials gather additional information about a drug's safety, efficacy, or optimal use. Phase Not Applicable. Describes trials without FDA-defined phases ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1094715924006627

A Comprehensive Review of Low-Intensity Focused ... Regardless, given LIFU has revealed a strong safety profile, research is rapidly moving beyond basic mechanistic studies to clinical trials to assess its impact ...