LIFU Neuromodulation for Opioid Use Disorder

Recruiting at 2 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

Trial Summary

What is the purpose of this trial?

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 neuromodulatory treatment for OUD (Opioid Use Disorder) and/or other Substance Use Disorders (SUDs) by assessing its safety and tolerability in subjects with OUD.

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 data supports the effectiveness of the treatment Exablate Model 4000 Type 2.0/2.1, Exablate Model 4000 Type 2.0/2.1, Exablate Neuro for opioid use disorder?

Research on noninvasive brain stimulation (NIBS) shows preliminary effectiveness for substance use disorders, suggesting that similar neuromodulation techniques might help with opioid use disorder. While specific data on the Exablate device for opioid use is limited, the general concept of brain stimulation has shown promise in related areas. ^{1 2 3 4 5}

How is LIFU Neuromodulation treatment different from other treatments for opioid use disorder?

LIFU Neuromodulation is unique because it uses noninvasive brain stimulation to potentially help treat opioid use disorder, unlike traditional treatments that often rely on medications or psychotherapy. This approach targets the brain directly, which may offer a new way to reduce cravings and prevent relapse without the use of drugs. ^{1 2 3 6 7}

Eligibility Criteria

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.

My kidney function is not normal.

I have severe high blood pressure or unstable heart conditions.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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 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]

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]

References

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

A Systematic Review of Noninvasive Brain Stimulation for Opioid Use Disorder. [2022]

2. Netherlands 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. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

A Novel Treatment of Opioid Cravings With an Effect Size of .73 for Unilateral Transcranial Photobiomodulation Over Sham. [2022]

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

Neural correlates of adherence to extended-release naltrexone pharmacotherapy in heroin dependence. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Opioid use and dropout from extended-release naltrexone in a controlled trial: implications for mechanism. [2022]

6. United States 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. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Neuromodulation and Opioid Use Disorder: Ethical Opportunities for Canada. [2023]