Episodic Future Thinking + Low-intensity Focused Ultrasound for Chronic Pain and Alcoholism

Overseen By Kirstin Gatchalian

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Polytechnic Institute and State University

Disqualifiers: Claustrophobia, Neurologic disorder, Pregnancy, others

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

Compensation: Varies

Number of Visits: 5

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have an active medical disorder or are undergoing treatment with potential effects on the central nervous system, you may be excluded from participating.

What data supports the effectiveness of this treatment for chronic pain and alcoholism?

Low-intensity focused ultrasound (LIFU) is a promising non-invasive treatment that can modulate brain activity and has shown potential in managing chronic pain by targeting specific brain regions. It is approved for certain types of pain management, and its ability to safely and precisely affect brain activity suggests it could be effective for conditions like chronic pain and possibly alcoholism. ^{1 2 3 4 5}

Is low-intensity focused ultrasound (LIFU) safe for humans?

Research suggests that low-intensity focused ultrasound (LIFU) is generally safe for humans, with studies showing it can modulate brain activity and manage pain with minimal side effects. However, more extensive studies are needed to confirm its safety across different conditions. ^{1 4 6 7 8}

How is the treatment of Episodic Future Thinking and Low-intensity Focused Ultrasound for chronic pain and alcoholism different from other treatments?

This treatment is unique because it combines mental exercises that focus on future and past thinking with low-intensity focused ultrasound, a non-invasive technique that uses sound waves to stimulate specific brain areas, potentially offering a novel way to address both the cognitive and emotional aspects of chronic pain and alcoholism. ^{9 10 11 12 13}

What is the purpose of this trial?

The objective of this within-subject study is to test the effects of Episodic Future Thinking (EFT) and Low-intensity Focused Ultrasound (LIFU) interventions on the pain of subjects who have chronic pain and alcohol use disorder(s).

Research Team

Warren K Bickel, PhD

Principal Investigator

Virginia Polytechnic and State University

Wynn Legon, PhD

Principal Investigator

Virginia Polytechnic and State University

Eligibility Criteria

This trial is for adults over 21 with chronic pain and alcohol use disorder, who are mentally and physically stable enough to complete a survey. They must not have unmanaged medical or psychiatric conditions, meet DSM-V criteria for alcoholism, and can't have MRI/CT contraindications like metal implants or be pregnant.

Inclusion Criteria

I experience chronic pain.

I feel mentally and physically stable enough to complete a survey.

Not have unmanaged medical or psychiatric conditions the survey

Exclusion Criteria

Failure to provide a Social Security Number or Tax ID number. This is required for tax purposes

I am claustrophobic, which may affect my ability to undergo scans.

You cannot participate if you are pregnant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Baseline and Imaging

Participants complete consent, MRI, and CT scans required for the LIFU intervention

1 day

1 visit (in-person)

Intervention Sessions

Participants complete three intervention sessions with EFT, LIFU, and control conditions

4-5 weeks

3 visits (in-person)

Follow-up

Participants are monitored for changes in delayed discounting, acute pain perception, chronic pain severity, alcohol valuation, and alcohol craving

1 week

Treatment Details

Interventions

• Episodic Future Thinking
• Episodic Recent Thinking
• Low-intensity Focused Ultrasound
• Sham Low-intensity Focused Ultrasound

Trial Overview The study tests how Episodic Future Thinking (EFT) and Low-intensity Focused Ultrasound (LIFU), compared to their control interventions (Episodic Recent Thinking and Sham LIFU), affect pain in people with chronic pain who also misuse alcohol.

Participant Groups

Group I: EFT and Sham LIFU Experimental Treatment 2 Interventions

Participants will generate positive recent past events that have happened to them at several time points in the previous day (e.g., 7pm-10pm, 4pm-7pm, 1pm-4pm, 10am-1pm, and 7am-10am). During Sham LIFU, the device will be set up identically as in real LIFU. However, the device will be turned off.

Group II: EFT and LIFU Experimental Treatment 2 Interventions

Participants will generate positive future events they are looking forward to at several time points in the future (e.g., 2 weeks, 1 month, 3 months, 1 year, and 5 years). During the LIFU condition, participants will have an ultrasound transducer placed on their head, where brief ultrasound pulses are delivered to the desired brain area using the imaging collected during visit 1. A small amount of ultrasound gel will be placed on the face of the single-element focused ultrasound transducer. The transducer will then be fitted on the scalp over the desired brain area and held in place with a mechanical arm. Brief pulses (0.2 to 2 seconds; duty cycle 10 - 70%; pulse repetition frequency 100 - 1000 Hz) of low-intensity (\< 50 W/cm2 Isppa), sub-thermal ultrasound (0.3 - 0.5 MHz) will be delivered in order to determine the area of activation, as well as the patterns of brain activity generated.

Group III: CET ad LIFU Experimental Treatment 2 Interventions

Participants will generate positive recent past events that have happened to them at several time points in the previous day (e.g., 7pm-10pm, 4pm-7pm, 1pm-4pm, 10am-1pm, and 7am-10am). During the LIFU condition, participants will have an ultrasound transducer placed on their head, where brief ultrasound pulses are delivered to the desired brain area using the imaging collected during visit 1.

Who Is Running the Clinical Trial?

Virginia Polytechnic Institute and State University

Lead Sponsor

Trials

162

Recruited

26,900+

Findings from Research

High-density gel polymer matrices are effective couplants for low-intensity focused ultrasound (LIFU) neuromodulation, showing low acoustic attenuation (3.3%) and minimal beam distortion, making them suitable for clinical use.

The study highlights the importance of using standardized methods for preparing these gels to ensure consistent performance, as factors like thickness and de-gassing can significantly affect acoustic transmission and pressure attenuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. Strohman, A., In, A., Stebbins, K., et al.[2023]

Focused ultrasound (FUS) is a promising noninvasive technique for managing chronic pain, with approved uses for thalamotomy in neuropathic pain and treatment of pain from bone metastases.

Different intensities of FUS can produce varying effects: low-intensity ultrasound (LILFUS) can facilitate or suppress neural activity, while high-intensity focused ultrasound (HIFU) can ablate tissue, showing potential for treating conditions like knee osteoarthritis and refractory chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications. di Biase, L., Falato, E., Caminiti, ML., et al.[2021]

The study developed a 3D printed, wearable helmet designed for Low-Intensity Focused Ultrasound (LIFU) that allows for precise and noninvasive brain stimulation, enhancing the accuracy of neuromodulation techniques.

Testing showed that the helmet effectively positions the target within the focal volume of the ultrasound, indicating its potential for improved spatial resolution in brain stimulation applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a subject-specific guide system for Low-Intensity Focused Ultrasound (LIFU) brain stimulation. Joe, H., Pahk, KJ., Park, S., et al.[2020]

Low intensity focused ultrasound (LIFU) is a promising non-invasive technology that can precisely modulate brain activity, offering a new approach to studying and potentially treating psychiatric illnesses.

LIFU has been shown to safely affect both cortical and subcortical brain regions, distinguishing it from other neuromodulatory techniques due to its spatial precision and reversible effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. Arulpragasam, AR., van 't Wout-Frank, M., Barredo, J., et al.[2022]

In a study involving 30 male Sprague Dawley rats with common peroneal nerve injury, low intensity focused ultrasound (liFUS) applied to the L5 dorsal root ganglion significantly altered neuronal activity, increasing pyramidal neuron spike frequency in the primary somatosensory cortex (SI) and reducing interneuron firing in the anterior cingulate cortex (ACC).

These changes in neuronal activity occurred 80 to 120 minutes after liFUS treatment and may correlate with improved sensory thresholds, suggesting a potential mechanism for how liFUS can help alleviate neuropathic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury. Bao, J., Byraju, K., Patel, VJ., et al.[2022]

Low intensity focused ultrasound (liFUS) can modulate pain responses without causing significant heating, as demonstrated in swine models, with magnetic resonance thermometry imaging (MRTI) effectively measuring temperature changes of less than 2.0 °C at the L5 dorsal root ganglion (DRG).

The study identified that referenceless MRTI is capable of accurately detecting small thermal changes, which is crucial for establishing safe parameters for future liFUS therapy in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR thermometry imaging for low intensity focused ultrasound modulation of spinal nervous tissue. Olinger, C., Vest, J., Tarasek, M., et al.[2023]

Low intensity focused ultrasound (LiFUS) can effectively disrupt the blood-brain barrier (BBB) in a dose-dependent manner, with increased tracer uptake in the brain observed when using higher microbubble and cavitation doses.

The timing of tracer administration is crucial; the highest accumulation of small solutes occurs when administered just before LiFUS, but significant uptake is also seen up to 6 hours post-treatment, indicating a biphasic response in BBB permeability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model. Arsiwala, TA., Sprowls, SA., Blethen, KE., et al.[2023]

Low-intensity focused ultrasound (LIFU) therapy significantly reduced cancer-related neuropathic pain in a retrospective study of 22 patients, with a p-value of less than 0.001 indicating strong statistical significance.

Approximately 76.5% of patients responded positively to LIFU therapy, suggesting it may be an effective treatment option for neuropathic pain, particularly that caused by chemotherapy, and it has a minimal side effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary effects of low-intensity focused ultrasound treatment program for cancer-related neuropathic pain. Patel, AA., Zhukosvky, M., Sidharthan, S., et al.[2022]

Brain imaging techniques have the potential to identify changes in the brain that could serve as biomarkers for chronic pain, which may improve drug development and treatment strategies for patients.

Future research should focus on imaging ongoing pain to enhance our understanding of brain function in various pain conditions and how different treatments affect these states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers for chronic pain and analgesia. Part 2: how, where, and what to look for using functional imaging. Borsook, D., Becerra, L., Hargreaves, R.[2015]

Chronic pain is closely linked with emotional and cognitive disorders, creating a cycle where each condition exacerbates the other, particularly seen in conditions like low back pain and fibromyalgia.

Brain imaging studies reveal that emotional and cognitive circuits overlap in areas of the brain that also control pain, suggesting that effective treatment for chronic pain must address these interconnected functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic pain: emotional and cognitive consequences]. Laurent, B.[2016]

In a study involving 16 adults with chronic pain, a home-based neurofeedback (NFB) device showed promising results, with 11 participants reporting pain relief and 8 experiencing clinically significant improvements after 32-48 training sessions over 8 weeks.

The NFB training led to significant reductions in central sensitization symptoms, improved sleep quality by nearly 50%, and decreased anxiety by 40%, all without any reported adverse events, indicating its safety and potential efficacy for managing chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Home-Based EEG Neurofeedback Intervention for the Management of Chronic Pain. Birch, N., Graham, J., Ozolins, C., et al.[2022]

Recent advances in brain-imaging techniques have improved our understanding of how chronic pain impacts various brain functions, including sensory, emotional, cognitive, and modulatory aspects.

Using brain imaging as a clinical tool could provide objective measures of disease state and treatment efficacy, potentially enhancing the management of chronic pain in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How close are we in utilizing functional neuroimaging in routine clinical diagnosis of neuropathic pain? Borsook, D., Becerra, L.[2021]

The fear-avoidance (FA) model of chronic pain is valid but needs to evolve to better account for complexities in disability and recovery, as well as personal goals that compete with pain management.

A proposed next generation of the FA model emphasizes a motivational perspective, focusing on how individuals' attempts to manage pain can interfere with their broader life goals and self-regulatory processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fear-avoidance model of chronic pain: the next generation. Crombez, G., Eccleston, C., Van Damme, S., et al.[2022]

References

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Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. [2023]

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Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications. [2021]

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Development of a subject-specific guide system for Low-Intensity Focused Ultrasound (LIFU) brain stimulation. [2020]

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Low Intensity Focused Ultrasound for Non-invasive and Reversible Deep Brain Neuromodulation-A Paradigm Shift in Psychiatric Research. [2022]

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The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury. [2022]

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MR thermometry imaging for low intensity focused ultrasound modulation of spinal nervous tissue. [2023]

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Characterization of passive permeability after low intensity focused ultrasound mediated blood-brain barrier disruption in a preclinical model. [2023]

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Preliminary effects of low-intensity focused ultrasound treatment program for cancer-related neuropathic pain. [2022]

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Biomarkers for chronic pain and analgesia. Part 2: how, where, and what to look for using functional imaging. [2015]

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[Chronic pain: emotional and cognitive consequences]. [2016]

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Home-Based EEG Neurofeedback Intervention for the Management of Chronic Pain. [2022]

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Fear-avoidance model of chronic pain: the next generation. [2022]