Focused Ultrasound for Opioid Use Disorder

(LIFU Trial)

Overseen By Krystian Burum, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington D.C. Veterans Affairs Medical Center

Must be taking: Buprenorphine, Methadone

Must not be taking: Benzodiazepines, Opiates

Disqualifiers: Neuropathic pain, Schizophrenia, Seizures, others

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: 2

Duration: 1 session

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to to inhibit the anterior insula (AI) with low intensity focused ultrasound (LIFU) to determine the causal role for the AI in pain processing, anxiety, and opiate cue-induced craving. The main question\[s\] it aims to answer are: * the safety and tolerability of LIFU delivered bilaterally to AI compared to sham stimulation in individuals with opiate use disorder (OUD), anxiety, and chronic back pain * the effects of LIFU vs sham on measures of pain processing, anxiety symptoms, and opiate cue-induced craving Participants will undergo anatomical MRI, neurological assessment, clinical assessment and patient query to assess the safety and tolerability of LIFU vs sham.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be in treatment for opioid use disorder with buprenorphine or methadone. Daily use of other opiates or benzodiazepines is not allowed.

How is Low Intensity Focused Ultrasound (LIFU) treatment different from other treatments for opioid use disorder?

Low Intensity Focused Ultrasound (LIFU) is a novel, noninvasive treatment that uses sound waves to target specific areas of the brain, which is different from traditional medications that are taken orally or injected. This approach may offer a new way to help manage opioid use disorder by potentially altering brain activity without the need for drugs. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Low Intensity Focused Ultrasound (LIFU) for Opioid Use Disorder?

A systematic review suggests that noninvasive brain stimulation, which is similar to LIFU, shows preliminary effectiveness for substance use disorders. This indicates that LIFU might also be a promising treatment for opioid use disorder. ^{3 6 7 8 9}

Who Is on the Research Team?

Mary Lee, MD

Principal Investigator

Washington D.C. Veterans Affairs Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with chronic back pain, anxiety, and opioid use disorder. Participants must undergo MRI and neurological assessments to ensure safety. Details on specific inclusion or exclusion criteria are not provided.

Inclusion Criteria

Meet the DSM-5 criteria for current opiate use disorder

Evidence of central sensitization as measured by the Widespread Pain/Symptom Severity Index (WPSSI) with specific score criteria

I have had chronic back pain for at least 3 months, with pain on most days in the last 6 months.

Exclusion Criteria

I have been diagnosed with schizophrenia or schizo-affective disorder.

I have had cancer spread, significant weight loss, inflammation disorders, or cauda equina syndrome.

I experience nerve pain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one session of low-intensity focused ultrasound (LIFU) or sham to the anterior insula (AI) to assess safety and tolerability

1 session

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and heart rate variability

1 hour post-treatment

1 visit (in-person)

Extension

Participants may continue to be monitored for additional data on the effects of LIFU on opiate cue-induced craving and pain modulation

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Low Intensity Focused Ultrasound (LIFU)

Trial Overview The study tests if low intensity focused ultrasound (LIFU) can safely target the anterior insula to affect pain, anxiety, and opioid cravings compared to a sham (fake) treatment.

How Is the Trial Designed?

Group I: Sham/LIFU Experimental Treatment 1 Intervention

double-blind, sham-controlled, crossover study in N=25 individuals with opiate use disorder, anxiety, and chronic back pain

Group II: LIFU/Sham Experimental Treatment 1 Intervention

double-blind, sham-controlled, crossover study in N=25 individuals with opiate use disorder, anxiety, and chronic back pain

Low Intensity Focused Ultrasound (LIFU) is already approved in United States, Canada for the following indications:

Approved in United States as Low-Intensity Focused Ultrasound for:

• Chronic Pain
• Opioid Use Disorder
• Anxiety Disorders

Approved in Canada as Low-Intensity Focused Ultrasound for:

• Chronic Pain
• Opioid Use Disorder
• Anxiety Disorders

Who Is Running the Clinical Trial?

Washington D.C. Veterans Affairs Medical Center

Lead Sponsor

Trials

45

Recruited

18,500+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

The Veterans Health Administration (VHA) identified critical research priorities to improve opioid safety for veterans, focusing on managing opioid use disorder, long-term opioid therapy, and co-occurring pain and substance use disorders.

Key recommendations include expanding access to medication treatment for opioid use disorder, implementing collaborative tapering programs for long-term opioid users, and conducting larger trials on behavioral and exercise interventions for pain management in patients with substance use disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Research Agenda for Advancing Strategies to Improve Opioid Safety: Findings from a VHA State of the Art Conference. Becker, WC., Krebs, EE., Edmond, SN., et al.[2021]

In a 24-week study involving 272 participants with prescription-type opioid use disorder, the flexible BUP/NX model of care significantly reduced cravings more than the standard methadone treatment.

Cravings decreased in both groups, but the BUP/NX group had lower overall cravings, especially noticeable as early as week 2, suggesting that this model may be more effective for managing cravings in opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine/naloxone and methadone effectiveness for reducing craving in individuals with prescription opioid use disorder: Exploratory results from an open-label, pragmatic randomized controlled trial. McAnulty, C., Bastien, G., Eugenia Socias, M., et al.[2022]

In a study involving 474 participants with opioid use disorder, both extended-release naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX) significantly reduced pain over 24 weeks, as measured by the EuroQol (EQ-5D).

Participants receiving XR-NTX experienced a greater reduction in pain compared to those on BUP-NX, with an odds ratio of 1.60, indicating that XR-NTX may be more effective for managing pain in individuals with opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Baseline- and treatment-associated pain in the X:BOT comparative effectiveness study of extended-release naltrexone versus buprenorphine-naloxone for OUD. Wang, AL., Shulman, M., Choo, TH., et al.[2022]

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]

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]

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]

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]

Methadone and buprenorphine-naloxone are effective long-term maintenance medications for opioid use disorders (OUDs), positively impacting the health of individuals with opioid addiction.

Despite their effectiveness, the use of buprenorphine and naltrexone is limited due to stigma and barriers in access to treatment, highlighting the need for improved education and resources in the medical community.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of opioid addiction treatment and related preclinical research. Kreek, MJ., Reed, B., Butelman, ER.[2023]

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]

Citations

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

A Research Agenda for Advancing Strategies to Improve Opioid Safety: Findings from a VHA State of the Art Conference. [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

Buprenorphine/naloxone and methadone effectiveness for reducing craving in individuals with prescription opioid use disorder: Exploratory results from an open-label, pragmatic randomized controlled trial. [2022]

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

Baseline- and treatment-associated pain in the X:BOT comparative effectiveness study of extended-release naltrexone versus buprenorphine-naloxone for OUD. [2022]

4. United States 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. [2022]

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

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

6. England pubmed.ncbi.nlm.nih.gov

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

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

Immunotherapeutic strategies for treating opioid use disorder and overdose. [2023]

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

Current status of opioid addiction treatment and related preclinical research. [2023]

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

Multifaceted Quality Improvement Initiative Improves Retention in Treatment for Youth with Opioid Use Disorder. [2022]