Ultrasound Therapy for Opioid Use Disorder

Overseen By Jennifer Marton

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Ali Rezai

Disqualifiers: Neurological disorders, Stroke, Schizophrenia, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Duration not specified

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help individuals with severe opioid use disorder (OUD) using Low-Intensity Focused Ultrasound (LIFU), which employs ultrasound waves. The researchers aim to determine if LIFU can target specific brain areas to reduce opioid cravings and improve symptoms. Participants will join one of two groups: one receiving the actual LIFU treatment and another receiving a sham (fake) treatment for comparison. The trial seeks individuals who have struggled with severe OUD for at least two years. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for OUD.

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 study team to get a clear answer.

What prior data suggests that this ultrasound therapy is safe for opioid use disorder?

Research has shown that Low-Intensity Focused Ultrasound (LIFU) is safe and well-tolerated in studies involving individuals with substance use disorders. One study used LIFU on the nucleus accumbens, a brain region involved in addiction, and it produced promising results without major side effects. Participants generally tolerated the treatment well, and it was deemed safe. Initial findings from other studies also support the safety of LIFU for individuals with opioid addiction. These studies suggest that LIFU could be a safe option for those considering participation in clinical trials for opioid use disorder treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard opioid use disorder treatments like medication-assisted therapies (e.g., methadone, buprenorphine, and naltrexone), LIFU, or Low-Intensity Focused Ultrasound, offers a non-invasive approach. LIFU stands out because it uses sound waves to target specific brain regions associated with addiction, potentially reducing cravings and withdrawal symptoms without the need for drugs. Researchers are excited about LIFU because it provides a novel mechanism of action that could complement existing therapies or offer an alternative for those who struggle with or prefer not to use medication. Additionally, LIFU's non-invasive nature means fewer side effects and a lower risk of dependency compared to traditional pharmacological treatments.

What evidence suggests that LIFU is effective for opioid use disorder?

Research has shown that low-intensity focused ultrasound (LIFU), which participants in this trial may receive, could be a promising treatment for opioid addiction. LIFU targets and alters activity in deep brain regions involved in addiction. This precise targeting may help reduce cravings and drug use in individuals with severe opioid addiction. Studies have found that LIFU is safe and well-tolerated, effectively influencing brain areas linked to reward and addiction. Early results suggest LIFU might transform the treatment of severe addiction, offering new hope for those unresponsive to other treatments. ^{1 4 5 6 7}

Who Is on the Research Team?

Ali Rezai

Principal Investigator

Executive Director WVU Rockefeller Neuroscience Institute

Are You a Good Fit for This Trial?

This trial is for adults aged 22-60 with severe opioid use disorder (OUD) that's lasted at least two years. Women who can have children must test negative for pregnancy and agree to use birth control. It's not suitable for those who don't meet these criteria.

Inclusion Criteria

Women of reproductive potential must have negative pregnancy test and agree to use acceptable forms of contraception

I am between 22 and 60 years old.

Fulfill current DSM-5 diagnostic criteria for severe OUD with at least a 2-year history

Exclusion Criteria

Unable to speak, read and understand English

Subject is considered to be a poor surgical or study candidate

I have a significant neurological condition.

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) or sham treatment targeting the NAc and VC

Duration not specified

Follow-up

Participants are monitored for changes in opioid use and treatment emergent adverse events

90 days

What Are the Treatments Tested in This Trial?

Interventions

• LIFU

Trial Overview The study tests Low Intensity Focused Ultrasound (LIFU) on the brain areas NAc and VC, comparing it with a sham (fake treatment) in people whose OUD hasn't improved with standard treatments. Participants are chosen randomly to receive either LIFU or the sham.

How Is the Trial Designed?

Group I: LIFU Treatment Experimental Treatment 1 Intervention

Group II: Sham treatment Placebo Group 1 Intervention

LIFU is already approved in United States for the following indications:

Approved in United States as Focused Ultrasound for:

• Essential Tremor
• Parkinson’s Disease

Who Is Running the Clinical Trial?

Ali Rezai

Lead Sponsor

Trials

6

Recruited

90+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Vaccines for opioid use disorder (OUD) are being explored as a novel treatment option that could complement existing medications, addressing barriers to treatment initiation and retention.

Promising results from preclinical trials suggest that opioid vaccines may provide protection against overdose and improve treatment outcomes, indicating a potential shift in how OUD is managed in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic strategies for treating opioid use disorder and overdose. Luba, R., Martinez, S., Jones, J., et al.[2023]

A pilot study involving three patients with long-standing opioid dependency showed that treatment with a high-intensity cold laser device allowed them to discontinue all opioid medications after 8-12 sessions over 3-4 weeks.

At follow-up 1-2 months later, these patients reported effective pain control using only over-the-counter non-opioid analgesics, suggesting that this non-pharmacologic approach may be a promising alternative for managing chronic pain and reducing opioid dependency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel treatment for chronic opioid use after surgery. White, PF., Elvir-Lazo, OL., Hernandez, H.[2018]

A randomized controlled trial with 50 participants showed that combining electroacupuncture with auricular point pressing significantly improved mental health scores compared to auricular point pressing alone, indicating enhanced quality of life for individuals undergoing methadone maintenance treatment.

The combined therapy also led to a greater reduction in methadone dosage, suggesting that this treatment approach may help in managing heroin use disorder more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Electroacupuncture Combined with Auricular Point Pressing in Improving Mental Well-Being among Individuals with Heroin Use Disorder: A Randomized Controlled Crossover Trial and Pilot Study. Yu, KC., Wei, HT., Chang, SC., et al.[2022]

In a retrospective overview of 42 patients with Opioid Use Disorders, 62% showed significant positive responses to unilateral transcranial photobiomodulation (UtPBM) as an adjunct therapy, indicating its potential efficacy in enhancing treatment outcomes.

The treatment was reported to be safe, with no significant side effects observed, aside from temporary anxiety in two patients that resolved with psychotherapy, suggesting that UtPBM could be a beneficial addition to existing therapies for OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unilateral transcranial photobiomodulation for opioid addiction in a clinical practice: A clinical overview and case series. Schiffer, F.[2021]

Implementing quality improvement processes, including motivational interviewing training and reduced initial treatment requirements, significantly improved the 6-month retention rate for adolescents and young adults in a medication-assisted treatment clinic for opioid use disorders.

Additional support measures like transportation assistance and incentive programs also led to a notable increase in the rate of patients returning for their second visit, highlighting the importance of accessibility and motivation in treatment engagement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multifaceted Quality Improvement Initiative Improves Retention in Treatment for Youth with Opioid Use Disorder. Cottrill, CB., Lemle, S., Matson, SC., et al.[2022]

Naltrexone, used as an adjuvant therapy for young heroin addicts, showed minimal side effects and was positively received by most participants, with 11 out of 16 patients rating it as somewhat or very positive after a six-month trial.

At a four-year follow-up, 6 out of 16 patients were rehabilitated without illegal substance use, suggesting that while naltrexone can enhance treatment, its long-term effectiveness may be limited and should be combined with other therapies like methadone maintenance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of naltrexone in the treatment of young drug addicts]. Waal, H., Aamodt, Ø., Olsen, H.[2013]

In a study of 164 rehabilitating heroin users treated with transcutaneous electrical acupoint stimulation (TEAS) for at least 3 months, 32.3% remained drug-free after 12 months, which is significantly higher than the typical relapse rate of less than 5% without further intervention.

The use of the Han's acupoint nerve stimulator (HANS) appears to effectively reduce relapse rates among detoxified heroin users, indicating its potential as a supportive treatment in addiction recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prospective study of Han's acupoint nerve stimulator for preventing relapse of detoxified heroin addicts]. Fang, J., Ma, D., Zhong, J., et al.[2019]

Acupuncture has shown potential benefits in treating opioid use disorder (OUD), particularly in reducing cravings, insomnia, and depression, based on a systematic review of nine studies with 1063 participants.

Electroacupuncture (EA) was found to significantly alleviate opioid cravings and depression symptoms, while transcutaneous acupoint electrical stimulation (TEAS) effectively improved insomnia and anxiety symptoms compared to sham treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Acupuncture for Treating Opioid Use Disorder in Adults: A Systematic Review and Meta-Analysis. Chen, Z., Wang, Y., Wang, R., et al.[2022]

Noninvasive brain stimulation (NIBS) shows potential as a novel treatment strategy for opioid use disorder (OUD), but current research is limited, with only five studies involving a total of 150 participants identified in a systematic review.

The studies utilized various NIBS techniques, including TMS and tDCS, to target issues like cue-induced craving and withdrawal symptoms, indicating that while promising, more extensive research is needed to fully understand the efficacy and mechanisms of NIBS in treating OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Noninvasive Brain Stimulation for Opioid Use Disorder. Ward, HB., Mosquera, MJ., Suzuki, J., et al.[2022]

Neuromodulation techniques, particularly transcranial magnetic stimulation, show promise in reducing substance cravings and improving treatment outcomes for individuals with substance use disorder, based on a review of various studies.

Several forms of neuromodulation, both invasive and non-invasive, are being explored as potential non-pharmacological treatments for substance use disorder, highlighting the need for further research to establish their efficacy and mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation, deep brain stimulation, and other forms of neuromodulation for substance use disorders: Review of modalities and implications for treatment. Mahoney, JJ., Hanlon, CA., Marshalek, PJ., et al.[2021]

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. fusfoundation.org fusfoundation.org/posts/focused-ultrasound-for-opioid-addiction-new-clinical-trial-results-published/

Focused Ultrasound for Opioid Addiction: New Clinical ... LIFU neuromodulation is an outpatient procedure that can precisely target and modulate deep brain structures implicated in addiction.

3. sciencedirect.com sciencedirect.com/science/article/pii/S000632232500023X

Exploring a Novel Treatment for Severe Opioid Use Disorder We evaluated the safety and feasibility of focused ultrasound (FUS) neuromodulation to reduce substance cravings and use in severe opioid and co ...

4. reporter.nih.gov reporter.nih.gov/project-details/10823599

3UH3DA047714-04S1 - NIH RePORTER We hypothesize that LIFU applied to the NAc will be safe and well- tolerated and will modulate the brain networks associated with reward and addiction, thereby ...

5. 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 ...

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/NCT06297200

Low-Intensity Focused Ultrasound and the Complex Patient Be in treatment for opioid use disorder (OUD) including buprenorphine or methadone. Meet the DSM-5 criteria for a current anxiety disorder: generalized anxiety ...