LIFU Neuromodulation for Opioid Use Disorder

Recruiting at 3 trial locations

Overseen By Michael Kaplitt, MD, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must not be taking: Anticoagulants, Antiplatelets, Avastin

Disqualifiers: Schizophrenia, Bipolar, Severe hypertension, others

Stay on Your Current Meds You can continue your current medications while participating

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores Low Intensity Focused Ultrasound (LIFU) as a new treatment option for individuals with Opioid Use Disorder (OUD) and other Substance Use Disorders (SUDs). The researchers aim to assess the safety and tolerability of this treatment when combined with existing care for these conditions. Participants will receive both real and placebo treatments, without knowing which is which, to evaluate LIFU's impact on their symptoms. The trial seeks individuals diagnosed with OUD or another SUD for at least two years who are already receiving treatment. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research in addiction treatment.

Do I need to stop my current medications for the trial?

The trial does not specify that you must stop taking your current medications. However, if you are on medications that might interact with the treatment, the study investigator will decide if you can participate. If you are on medication for opioid or alcohol use disorder, you need to be on a stable dose for at least 7 days before the procedure.

What prior data suggests that this device is safe for neuromodulation in opioid use disorder?

Research is exploring the safety of using Low Intensity Focused Ultrasound (LIFU) with the Exablate Model 4000 Type 2.0/2.1 to treat Opioid Use Disorder (OUD). An earlier study aimed to ensure the treatment's safety by observing patient responses and noting any side effects.

The same device, known as Exablate Neuro, has already received FDA approval for treating essential tremor, indicating it is generally safe for people. While this does not guarantee safety for OUD treatment, it offers some reassurance about the device itself.

Overall, studies aim to demonstrate that this new use of the Exablate is well-tolerated, meaning most people can handle it without serious issues. However, like any treatment, some side effects might occur, and ongoing research is crucial to fully understand its safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the LIFU neuromodulation technique using the Exablate Model 4000 because it offers a non-invasive approach to treating opioid use disorder. Unlike traditional treatments, which often involve medication-assisted therapy with drugs like methadone or buprenorphine, this method uses low-intensity focused ultrasound (LIFU) to modulate brain activity. This innovative technique could potentially reduce cravings and withdrawal symptoms without the side effects associated with medication. Additionally, the use of a sham-controlled design allows for a more accurate assessment of the treatment's true effectiveness, providing hope for a novel intervention in addiction therapy.

What evidence suggests that this device is effective for Opioid Use Disorder?

Research has shown that Low Intensity Focused Ultrasound (LIFU) using the Exablate Model 4000 Type 2.0/2.1 may help treat opioid use disorder (OUD). Early studies suggest this method could reduce cravings and addictive behaviors. In this trial, participants will undergo both sham and active treatments with the Exablate device, with subjects unaware of the treatment order. The Exablate device has already successfully treated conditions like essential tremor, suggesting it might also address nerve-related issues. While specific results for OUD are still under study, the device's success with other brain disorders indicates potential benefits for those dealing with opioid addiction. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for right-handed males and females aged 18-60 with Opioid Use Disorder who are part of the WVU Comprehensive Opioid Addiction Treatment Program, have been abstinent for 90 days, and on stable medication. Excluded are those with severe health issues, other clinical trials participation, non-English speakers, pregnancy or planning to be pregnant, certain medication use, inability to stay still for treatment duration, bleeding disorders or mental health conditions.

Inclusion Criteria

I am willing to follow the study's requirements and attend all visits.

Subject has signed and received a copy of the approved informed consent form

Subject has been off opioids and other illicit substances, except for cannabis, confirmed via urine toxicology screen

Exclusion Criteria

You have objects implanted in your skull or brain.

I do not have any CNS infections, HIV, or Hepatitis C.

My kidney function is not normal.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Subjects undergo both sham and active ExAblate treatments with enhanced intensity

4 weeks

Multiple visits for treatment sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Exablate Model 4000 Type 2.0/2.1

Trial Overview The study tests Low Intensity Focused Ultrasound (LIFU) using the Exablate Model 4000 Type 2.0/2.1 as an additional treatment method for OUD by evaluating its safety and how well subjects can tolerate it.

How Is the Trial Designed?

Group I: Sham/Active ExAblate Treatment Stage 1 and 2 Experimental Treatment 1 Intervention

Subject will undergo both Treatment 1 (sham) and Treatment 2 (with enhanced intensity). Subjects are blinded to the order of the sham vs active treatment.

Who Is Running the Clinical Trial?

InSightec

Lead Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Published Research Related to This Trial

A novel treatment using unilateral transcranial photobiomodulation (t-PBM) significantly reduced opioid cravings by 51% one week after treatment, compared to only 15.8% reduction from a sham treatment, indicating its efficacy in addressing opioid use disorders.

The active t-PBM treatment also led to significant improvements in depression and anxiety scores, demonstrating its potential as a safe and effective intervention for individuals with opioid cravings and related mental health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel Treatment of Opioid Cravings With an Effect Size of .73 for Unilateral Transcranial Photobiomodulation Over Sham. Schiffer, F., Reichmann, W., Flynn, E., 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]

The opioid crisis in British Columbia has reached unprecedented levels, with overdose deaths in 2021 being the highest ever recorded, highlighting the urgent need for effective interventions.

Neuromodulation techniques like deep brain stimulation and repetitive transcranial magnetic stimulation show promise as treatments for opioid use disorder, but face challenges related to stigma, fear, and access, particularly in marginalized communities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation and Opioid Use Disorder: Ethical Opportunities for Canada. Boyle, Q., Illes, J.[2023]

A study involving 32 detoxified heroin-dependent individuals used fMRI to explore the neural correlates of adherence to injectable extended-release naltrexone (XRNTX), revealing that brain activity in the medial prefrontal cortex predicted how many XRNTX injections participants received.

Despite varying adherence levels, the incidence of opioid-positive urine tests was low during XRNTX treatment, suggesting that XRNTX is effective in reducing opioid use, although concurrent use of other substances like tobacco and cocaine may complicate treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence. Wang, AL., Elman, I., Lowen, SB., et al.[2021]

In a 24-week trial involving 250 adults with opioid use disorder, extended-release naltrexone (XR-NTX) significantly reduced the risk of treatment dropout after episodes of opioid use compared to placebo, indicating its effectiveness in maintaining treatment adherence.

Patients receiving XR-NTX had a higher completion rate without positive urine drug tests (31%) compared to those on placebo (20%), suggesting that XR-NTX may help sustain abstinence, although the difference was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid use and dropout from extended-release naltrexone in a controlled trial: implications for mechanism. Nunes, EV., Bisaga, A., Krupitsky, E., et al.[2022]

The NET Device is a non-invasive treatment designed to help people with opioid use disorder (OUD) quit opioids without medication, and it is currently being tested in a clinical trial with 100 participants (50 receiving active treatment and 50 receiving sham treatment).

The trial aims to determine the safety and effectiveness of the NET Device by measuring the percentage of weeks participants remain abstinent from illicit opioids over a 12-week period, providing a potential new approach to treating OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, sham-controlled, quintuple-blinded trial to evaluate the NET device as an alternative to medication for promoting opioid abstinence. Greenwald, MK., Ghosh, S., Winston, JR.[2022]

The auricular neuromodulation device (NSS-2 Bridge) was used off-label in 5 patients after knee and hip surgeries, showing promising results in reducing pain and opioid use during recovery.

Patients reported low pain levels (median 0 to 2 on a 0-10 scale) and minimal oxycodone consumption (median 0 to 2.5 mg) post-surgery, with one patient completely avoiding opioids, suggesting the device may effectively provide analgesia and reduce reliance on opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Auricular Nerve Stimulation (Neuromodulation) for Analgesia and Opioid-Sparing Following Knee and Hip Arthroplasty: A Proof-of-Concept Case Series. Finneran, JJ., Said, ET., Ball, ST., et al.[2023]

Citations

1. ctv.veeva.com ctv.veeva.com/study/exablate-for-lifu-neuromodulation-in-patients-with-opioid-use-disorder-oud

Exablate for LIFU Neuromodulation in Patients With Opioid ... The purpose of this clinical trial is to investigate Low Intensity Focused Ultrasound (LIFU) using the Exablate® Model 4000 Type 2.0/2.1 as an adjunctive ...

2. fusfoundation.org fusfoundation.org/posts/focused-ultrasound-for-opioid-use-disorder-first-patient-treated-in-new-trial/

Focused Ultrasound for Opioid Use Disorder: First Patient ... The study aims to evaluate the safety and efficacy of using Insightec's Exablate Neuro focused ultrasound device to reduce substance cravings and addictive ...

3. insightec.com insightec.com/news/nejm-publishes-results/

NEJM Publishes Exablate Neuro Clinical Results The study met its primary endpoint with patients treated with Exablate Neuro demonstrating a clinically significant 47% improvement in a composite tremor score ...

4. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150038B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The ExAblate Neuro is intended for use in the unilateral Thalamotomy treatment of idiopathic Essential Tremor patients with medication-refractory ...

5. withpower.com withpower.com/trial/phase-opioid-related-disorders-10-2019-205cc

LIFU Neuromodulation for Opioid Use Disorder This N/A medical study run by InSightec is evaluating whether Exablate Model 4000 Type 2.0/2.1 will have tolerable side effects & efficacy for patients with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06474026

Study Details | NCT06474026 | A Clinical Trial to Evaluate ... This clinical trial aims to evaluate the safety and efficacy of neuromodulation using 'ExAblate 4000 Type 2.1' in patients with psychostimulant use disorder ...

7. researchgate.net researchgate.net/publication/387889426_Focused_Ultrasound_Neuromodulation_Exploring_a_Novel_Treatment_for_Severe_Opioid_Use_Disorder

Exploring a Novel Treatment for Severe Opioid Use Disorder The primary study endpoint was safety; secondary/exploratory outcomes included opioid and other substance use, substance craving, and ...