Opioid Use DisorderLIFUNCT06453109
Focused Ultrasound for the Complex Patient
A study testing low intensity focused ultrasound (LIFU) in people with Opioid Use Disorder and Chronic Back Pain, run by Washington D.C. Veterans Affairs Medical Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Opioid Use Disorder, Chronic Back Pain, Anxiety
- What is being tested?
- low intensity focused ultrasound (LIFU)
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Apr 2024to 30 Sep 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males and females aged 18-75 years
- Current diagnosis of Chronic Back Pain as defined by pain duration of at least three months, with back pain being an ongoing problem for at least half the days of the last six months.
- Have evidence of central sensitization (CS) as measured by the Widespread Pain/Symptom Severity Index (WPSSI) with a score of Widespread Pain Index (WPI) ≥ 7 and Symptom Severity (SS) ≥ 5 or WPI = 3-6 and SS ≥ 9.
- Participants must rate pain intensity at 4/10 or greater on the Brief Pain Inventory-Short Form (BPI-SF)
- Meet the DSM-5 criteria for current opiate use disorder as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
- Be in treatment for OUD including buprenorphine or methadone.
- Meet the DSM-5 criteria for a current anxiety disorder: generalized anxiety disorder, post-traumatic stress disorder or social anxiety disorder as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition(DSM-5).
Who cannot join
- Evidence of neuropathic pain
- Current DSM-5 substance use disorder other than OUD, tobacco use disorder
- Current DSM-5 diagnosis of schizophrenia or schizo-affective disorder
- Pregnant or breastfeeding
- Daily use of benzodiazepines or opiates (other than buprenorphine or methadone)
- History of seizures, neurologic disorders, including cerebrovascular disease, history of stroke, brain surgery, brain tumor, multiple sclerosis, or neurodegenerative diseases. They will not have history of metastasizing cancers, inflammatory disorder: rheumatoid arthritis, polymyalgia rheumatica, scleroderma, lupus or polymyositis, unintended weight loss of 20 pounds or more in the last year, or cauda equina syndrome.
- Ferromagnetic implants or other contraindications for MRI
- Unstable medical conditions such as congestive heart failure, unstable angina, poorly controlled arrhythmia active systemic infection end stage renal disease.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Krystian Burum, MS contact
United States1 site, 1 recruiting
- Recruiting
Washington DC Veterans Affairs Medical Center
Washington D.C., District of Columbia, 20422
Mary R Lee, MD, (202) 745-8000 ext. 58128, mary.lee3@va.gov
Mary R Lee, MD
About this study
Official title: Towards Treatment of the Complex Patient: Investigations of Low-intensity Focused Ultrasound
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.
Read the detailed description
Opioid use disorder with co-morbid chronic pain and anxiety is a clinical triad associated with the highest risk of opiate overdose deaths. Co-occurrence of these three disorders amplifies symptoms of each and results in poorer treatment outcomes. There are shared neurobiological substrates for these disorders such as reward processing and stress response. The anterior insula (AI) is a brain region involved in these processes as well as in clinical disorder of pain, addiction, and anxiety. The AI is upregulated in pain, addiction and anxiety disorders and is therefore a potential therapeutic target for neuromodulation. Low-intensity focused ultrasound (LIFU) is a noninvasive method to inhibit cortical and deep brain regions. LIFU can reach deep brain regions such as the AI with spatial specificity, unlike traditional noninvasive neuromodulation methods which lack spatial specificity and depth penetration. LIFU can selectively target the insula and its subregions and provides a potentially transformative method to reduce symptoms of pain, opiate craving, and anxiety in a complex patient population such as co-morbid chronic pain, anxiety, and opioid use disorder. In this study, the investigators will administer one session of inhibitory LIFU to the AI in individuals with opiate use disorder, chronic back pain, and anxiety disorders (generalized anxiety disorder, post-traumatic stress disorder, or social anxiety disorder)]. The aim of this phase of the study is to establish that LIFU vs sham LIFU to AI is safe and well tolerated as measured by adverse events, clinical evaluation and repeated structural brain magnetic resonance imaging scans. The investigators will also gather preliminary data on the effect of LIFU to AI on opiate cue-induced craving and laboratory measures of central sensitization(CS) which occurs with pain chronicity such as temporal summation of pain and conditioned pain modulation. There is a need for improved treatments for complex patients such as co-morbid chronic back pain, anxiety, and opioid use disorder beyond combining treatments for each disorder. LIFU provides an ability to transiently and selectively inhibit AI to determine its causal role in co-morbid chronic back pain, anxiety, and opioid use disorder symptoms which then may lead to improved treatments for this clinical triad which is associated with poor treatment outcomes.
- Conditions
- Opioid Use Disorder, Chronic Back Pain, Anxiety
- Being tested
- low intensity focused ultrasound (LIFU)
- Keywords
- anxiety disorders, oud, opiate use disorder, opioid, back pain, chronic back pain, opioid use, opioid abuse, opioid disorder, low intensity focused ultrasound, transcranial ultrasound
- Medical subject headings
- Opioid-Related Disorders, Anxiety Disorders, Back Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
low intensity focused ultrasound (LIFU)Device
Low-intensity focused ultrasound (LIFU) provides an energy source with millimeter resolution that can be focused anywhere in the brain safely and effectively for non-invasive and transient neuromodulation. LIFU is an important advance and of great significance for brain-mapping efforts, diagnostics, and therapies in neuroscience and particularly promising for addiction therapy as it provides unprecedented non-surgical access to the brain regardless of depth.
Much lower intensities of focused ultrasound (LIFU) are used so that tissue damage does not occur, but neural activity can be modulated. LIFU utilizes acoustic energy at much lower levels to affect tissue by mechanical effects.
| Study group | Role | What they receive |
|---|---|---|
| LIFU/Sham | Other | double-blind, sham-controlled, crossover study in N=25 individuals with opiate use disorder, anxiety, and chronic back pain Receives: Device: low intensity focused ultrasound (LIFU) |
| Sham/LIFU | Other | double-blind, sham-controlled, crossover study in N=25 individuals with opiate use disorder, anxiety, and chronic back pain Receives: Device: low intensity focused ultrasound (LIFU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events
number of adverse events
Measured: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
Secondary outcomes (2)
Heart rate variability
Continuous heart rate variability monitoring
Measured: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
Pain threshold
Numeric Pain Rating Scale (NPRS) Score: 0-10 0 = 'No pain' 10 = 'Worst pain imaginable'
Measured: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2024
- Study start29 Apr 2024
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- within subject, randomized, double-blind, sham-controlled trial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington D.C. Veterans Affairs Medical Center
- Sponsor type
- US federal agency
- Collaborators
- National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Mary R Lee, MD, Principal investigator, Washington D.C. Veterans Affairs Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06453109
- Sponsor's protocol ID
- 1777666
- Other IDs
- UG3DA059407
- Acronym
- LIFU
- Status last verified
- Nov 2024
- First submitted
- 5 Jun 2024
- Last updated
- 20 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: behavioral and imaging data
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Towards Treatment of the Complex Patient: Investigations of Low-intensity Focused Ultrasound
- ClinicalTrials.gov ID
- NCT06453109
- Acronym / sponsor ID
- LIFU / 1777666
- Conditions
- Opioid Use Disorder, Chronic Back Pain, Anxiety
- Keywords
- anxiety disorders, oud, opiate use disorder, opioid, back pain, chronic back pain, opioid use, opioid abuse
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Washington D.C. Veterans Affairs Medical CenterUS federal agency
- Collaborators
- National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)
- Study start
- 29 Apr 2024 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 11 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Opioid use disorder with co-morbid chronic pain and anxiety is a clinical triad associated with the highest risk of opiate overdose deaths. Co-occurrence of these three disorders amplifies symptoms of each and results in poorer treatment outcomes. There are shared neurobiological substrates for these disorders such as reward processing and stress response. The anterior insula (AI) is a brain region involved in these processes as well as in clinical disorder of pain, addiction, and anxiety. The AI is upregulated in pain, addiction and anxiety disorders and is therefore a potential therapeutic target for neuromodulation. Low-intensity focused ultrasound (LIFU) is a noninvasive method to inhibit cortical and deep brain regions. LIFU can reach deep brain regions such as the AI with spatial specificity, unlike traditional noninvasive neuromodulation methods which lack spatial specificity and depth penetration. LIFU can selectively target the insula and its subregions and provides a potentially transformative method to reduce symptoms of pain, opiate craving, and anxiety in a complex patient population such as co-morbid chronic pain, anxiety, and opioid use disorder. In this study, the investigators will administer one session of inhibitory LIFU to the AI in individuals with opiate use disorder, chronic back pain, and anxiety disorders (generalized anxiety disorder, post-traumatic stress disorder, or social anxiety disorder)]. The aim of this phase of the study is to establish that LIFU vs sham LIFU to AI is safe and well tolerated as measured by adverse events, clinical evaluation and repeated structural brain magnetic resonance imaging scans. The investigators will also gather preliminary data on the effect of LIFU to AI on opiate cue-induced craving and laboratory measures of central sensitization(CS) which occurs with pain chronicity such as temporal summation of pain and conditioned pain modulation. There is a need for improved treatments for complex patients such as co-morbid chronic back pain, anxiety, and opioid use disorder beyond combining treatments for each disorder. LIFU provides an ability to transiently and selectively inhibit AI to determine its causal role in co-morbid chronic back pain, anxiety, and opioid use disorder symptoms which then may lead to improved treatments for this clinical triad which is associated with poor treatment outcomes.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- within subject, randomized, double-blind, sham-controlled trial
| Arm | Type | Receives |
|---|---|---|
| LIFU/Sham | Other | Device: low intensity focused ultrasound (LIFU)double-blind, sham-controlled, crossover study in N=25 individuals with opiate use disorder, anxiety, and chronic back pain |
| Sham/LIFU | Other | Device: low intensity focused ultrasound (LIFU)double-blind, sham-controlled, crossover study in N=25 individuals with opiate use disorder, anxiety, and chronic back pain |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Males and females aged 18-75 years
- Current diagnosis of Chronic Back Pain as defined by pain duration of at least three months, with back pain being an ongoing problem for at least half the days of the last six months.
- Have evidence of central sensitization (CS) as measured by the Widespread Pain/Symptom Severity Index (WPSSI) with a score of Widespread Pain Index (WPI) ≥ 7 and Symptom Severity (SS) ≥ 5 or WPI = 3-6 and SS ≥ 9.
- Participants must rate pain intensity at 4/10 or greater on the Brief Pain Inventory-Short Form (BPI-SF)
- Meet the DSM-5 criteria for current opiate use disorder as diagnosed by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition.
Key exclusion criteria (8 listed)
- Evidence of neuropathic pain
- Current DSM-5 substance use disorder other than OUD, tobacco use disorder
- Current DSM-5 diagnosis of schizophrenia or schizo-affective disorder
- Pregnant or breastfeeding
- Daily use of benzodiazepines or opiates (other than buprenorphine or methadone)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| low intensity focused ultrasound (LIFU)Low-intensity focused ultrasound (LIFU) provides an energy source with millimeter resolution that can be focused anywhere in the brain safely and effectively for non-invasive and transient neuromodulation. LIFU is an important advance and of great significance for brain-mapping efforts, diagnostics, and therapies in neuroscience and particularly promising for addiction therapy as it provides unprecedented non-surgical access to the brain regardless of depth. Much lower intensities of focused ultrasound (LIFU) are used so that tissue damage does not occur, but neural activity can be modulated. LIFU utilizes acoustic energy at much lower levels to affect tissue by mechanical effects. | Device | LIFU/Sham, Sham/LIFU |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
number of adverse events
2 secondary outcomes
Heart rate variability
Time frame: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
Pain threshold
Time frame: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2024.
- Individual participant dataSharing planned: Yes. behavioral and imaging data
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Krystian Burum, MS contact
Mary R Lee, MD principal investigator
Washington D.C. Veterans Affairs Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing low intensity focused ultrasound (LIFU) in people with Opioid Use Disorder and Chronic Back Pain, run by Washington D.C. Veterans Affairs Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mary R Lee, MD (202-745-8000 ext. 58128, mary.lee3@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events (time frame: immediately prior to 1 session low-intensity focused ultrasound (LIFU) and within 1 hour post LIFU; immediately prior to 1 session sham and with in 1 hour post sham). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2024.