Ultrasound Stimulation for Neuropathic Pain
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: University of Utah
Disqualifiers: Poorly managed condition, Pregnant, Implanted device, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This study will apply low-intensity transcranial focused ultrasound to dorsal root ganglia in patients with chronic neuropathic pain. The target will be validated using magnetic resonance imaging. The stimulation will first be delivered using a range of stimulation parameters during psychophysical and physiological monitoring. A well-tolerated stimulation protocol will be selected for subsequent testing in a blinded randomized sham-controlled cross-over trial. The level of pain will be evaluated using the Numerical Rating Scale (NSR-11) and the Patient-Reported Outcomes Measurement Information System (PROMIS) numerical rating scales of pain.
Will I have to stop taking my current medications?
No, you will not have to stop taking your current medications. The study requires that you avoid changes to your current treatments for the duration of the study.
What data supports the effectiveness of this treatment for neuropathic pain?
Research shows that low-intensity focused ultrasound (liFUS) can reduce pain by affecting nerve activity and inflammation, and a study found that low-energy focused ultrasound reduced pain levels in patients with chronic neuropathic pain without side effects. This suggests that ultrasound treatments may be effective for managing neuropathic pain.
12345Is ultrasound stimulation safe for humans?
Research shows that low-intensity focused ultrasound (LIFU) is generally safe for humans, with no serious adverse effects reported. Some participants experienced mild symptoms like neck pain and sleepiness, similar to other non-invasive brain stimulation methods.
26789How is the ultrasound treatment for neuropathic pain different from other treatments?
This ultrasound treatment is unique because it uses low-intensity focused ultrasound (LIFU) to non-invasively target specific brain areas or nerves, potentially reducing pain without the need for surgery or medication. It offers a novel approach by modulating nerve activity and has shown promise in reducing pain levels with minimal side effects.
1241011Eligibility Criteria
This trial is for individuals with a primary diagnosis of chronic neuropathic pain that's been ongoing for at least two months. Participants should be willing to stick to their current treatments without changes and, if female and able to have children, must not be pregnant or agree to use effective contraception.Inclusion Criteria
For females of reproductive potential: negative pregnancy test or use of highly effective contraception for at least 1 month prior to baseline; agreement to use such a method throughout the study
I have had chronic pain for at least 2 months.
I have been primarily diagnosed with chronic pain.
+2 more
Exclusion Criteria
Implanted device in the back
Pregnant or breast feeding
Clinically inappropriate for participation in the study as determined by the study team
+2 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Low-intensity transcranial focused ultrasound is applied to the dorsal root ganglia with psychophysical and physiological monitoring
1 week
Daily visits during the intervention
Follow-up
Participants are monitored for pain intensity using NRS-11 and PROMIS scales
1 week
Daily assessments
Participant Groups
The study tests low-intensity focused ultrasound on dorsal root ganglia in patients with chronic pain, using MRI validation. It involves initial testing of various stimulation parameters followed by a blinded comparison between real and sham (fake) stimulations to see which reduces pain better.
2Treatment groups
Active Control
Placebo Group
Group I: Active stimulationActive Control1 Intervention
Low-intensity focused ultrasound stimulation of dorsal root ganglion involved in pain conduction
Group II: Sham stimulationPlacebo Group1 Intervention
Zero-intensity focused ultrasound stimulation of dorsal root ganglion involved in pain conduction
Low-frequency ultrasonic transducer is already approved in United States for the following indications:
🇺🇸 Approved in United States as Low-intensity transcranial focused ultrasound for:
- Chronic neuropathic pain
- Radiculopathy (sciatica)
- Spinal cord injury
- Phantom limb pain
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of UtahSalt Lake City, UT
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Who Is Running the Clinical Trial?
University of UtahLead Sponsor
References
Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model. [2018]Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system.
The effects of low intensity focused ultrasound on neuronal activity in pain processing regions in a rodent model of common peroneal nerve injury. [2022]Non-invasive, external low intensity focused ultrasound (liFUS) offers promise for treating neuropathic pain when applied to the dorsal root ganglion (DRG).
Focused Ultrasound (FUS) for Chronic Pain Management: Approved and Potential Applications. [2021]Chronic pain is one of the leading causes of disability and disease burden worldwide, accounting for a prevalence between 6.9% and 10% in the general population. Pharmacotherapy alone results ineffective in about 70-60% of patients in terms of a satisfactory degree of pain relief. Focused ultrasound is a promising tool for chronic pain management, being approved for thalamotomy in chronic neuropathic pain and for bone metastases-related pain treatment. FUS is a noninvasive technique for neuromodulation and for tissue ablation that can be applied to several tissues. Transcranial FUS (tFUS) can lead to opposite biological effects, depending on stimulation parameters: from reversible neural activity facilitation or suppression (low-intensity, low-frequency ultrasound, LILFUS) to irreversible tissue ablation (high-intensity focused ultrasounds, HIFU). HIFU is approved for thalamotomy in neuropathic pain at the central nervous system level and for the treatment of facet joint osteoarthritis at the peripheral level. Potential applications include HIFU at the spinal cord level for selected cases of refractory chronic neuropathic pain, knee osteoarthritis, sacroiliac joint disease, intervertebral disc nucleolysis, phantom limb, and ablation of peripheral nerves. FUS at nonablative dosage, LILFUS, has potential reversible and tissue-selective effects. FUS applications at nonablative doses currently are at a research stage. The main potential applications include targeted drug and gene delivery through the Blood-Brain Barrier, assessment of pain thresholds and study of pain, and reversible peripheral nerve conduction block. The aim of the present review is to describe the approved and potential applications of the focused ultrasound technology in the field of chronic pain management.
Low-Energy Transcranial Navigation-Guided Focused Ultrasound for Neuropathic Pain: An Exploratory Study. [2023]Neuromodulation using high-energy focused ultrasound (FUS) has recently been developed for various neurological disorders, including tremors, epilepsy, and neuropathic pain. We investigated the safety and efficacy of low-energy FUS for patients with chronic neuropathic pain. We conducted a prospective single-arm trial with 3-month follow-up using new transcranial, navigation-guided, focused ultrasound (tcNgFUS) technology to stimulate the anterior cingulate cortex. Eleven patients underwent FUS with a frequency of 250 kHz and spatial-peak temporal-average intensity of 0.72 W/cm2. A clinical survey based on the visual analog scale of pain and a brief pain inventory (BPI) was performed during the study period. The average age was 60.55 ± 13.18 years-old with a male-to-female ratio of 6:5. The median current pain decreased from 10.0 to 7.0 (p = 0.021), median average pain decreased from 8.5 to 6.0 (p = 0.027), and median maximum pain decreased from 10.0 to 8.0 (p = 0.008) at 4 weeks after treatment. Additionally, the sum of daily life interference based on BPI was improved from 59.00 ± 11.66 to 51.91 ± 9.18 (p = 0.021). There were no side effects such as burns, headaches, or seizures, and no significant changes in follow-up brain magnetic resonance imaging. Low-energy tcNgFUS could be a safe and noninvasive neuromodulation technique for the treatment of chronic neuropathic pain.
Effects of external low intensity focused ultrasound on inflammatory markers in neuropathic pain. [2021]Changes in inflammatory cytokine levels contribute to the induction and maintenance of neuropathic pain. We have shown that external low intensity focused ultrasound (liFUS) reduces allodynia in a common peroneal nerve injury (CPNI). Here, we investigate an underlying mechanism of action for this treatment and measure the effect of liFUS on inflammatory markers.
Focused ultrasound-mediated non-invasive brain stimulation: examination of sonication parameters. [2022]Transcranial focused ultrasound (FUS) has emerged as a new brain stimulation modality. The range of sonication parameters for successful brain stimulation warrants further investigation.
A retrospective qualitative report of symptoms and safety from transcranial focused ultrasound for neuromodulation in humans. [2021]Low intensity transcranial focused ultrasound (LIFU) is a promising method of non-invasive neuromodulation that uses mechanical energy to affect neuronal excitability. LIFU confers high spatial resolution and adjustable focal lengths for precise neuromodulation of discrete regions in the human brain. Before the full potential of low intensity ultrasound for research and clinical application can be investigated, data on the safety of this technique is indicated. Here, we provide an evaluation of the safety of LIFU for human neuromodulation through participant report and neurological assessment with a comparison of symptomology to other forms of non-invasive brain stimulation. Participants (N = 120) that were enrolled in one of seven human ultrasound neuromodulation studies in one laboratory at the University of Minnesota (2015-2017) were queried to complete a follow-up Participant Report of Symptoms questionnaire assessing their self-reported experience and tolerance to participation in LIFU research (Isppa 11.56-17.12 W/cm2) and the perceived relation of symptoms to LIFU. A total of 64/120 participant (53%) responded to follow-up requests to complete the Participant Report of Symptoms questionnaire. None of the participants experienced serious adverse effects. From the post-hoc assessment of safety using the questionnaire, 7/64 reported mild to moderate symptoms, that were perceived as 'possibly' or 'probably' related to participation in LIFU experiments. These reports included neck pain, problems with attention, muscle twitches and anxiety. The most common unrelated symptoms included sleepiness and neck pain. There were initial transient reports of mild neck pain, scalp tingling and headache that were extinguished upon follow-up. No new symptoms were reported upon follow up out to 1 month. The profile and incidence of symptoms looks to be similar to other forms of non-invasive brain stimulation.
MR thermometry imaging for low intensity focused ultrasound modulation of spinal nervous tissue. [2023]Previously in rodent and swine models, we have shown that external low intensity focused ultrasound (liFUS) can be used to modulate pain responses. To ensure no adverse heating events occur with liFUS modulation in a non-invasive manner, we perform initial work in swine to show that magnetic resonance thermometry imaging (MRTI) is capable of measuring
Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. [2023]Ultrasound is an important theragnostic modality in modern medicine. Technical advancement of both acoustic focusing and transcranial delivery have enabled administration of ultrasound waves to localized brain areas with few millimeters of spatial specificity and penetration depth sufficient to reach the thalamus. Transcranial focused ultrasound (tFUS) given at a low acoustic intensity has been shown to increase or suppress the excitability of region-specific brain areas. The neuromodulatory effects can outlast the sonication, suggesting the possibility of inducing neural plasticity needed for neurorehabilitation. Increasing numbers of studies have shown the efficacy and excellent safety profile of the technique, yet comparisons among the safety-related parameters have not been compiled. This review aims to provide safety information and perspectives of tFUS brain stimulation. First, the acoustic parameters most relevant to thermal/mechanical tissue damage are discussed along with regulated parameters for existing ultrasound therapies/diagnostic imaging. Subsequently, the parameters used in studies of large animals, non-human primates, and humans are surveyed and summarized in terms of the acoustic intensity and the mechanical index. The pulse-mode operation and the use of low ultrasound frequency for tFUS-mediated brain stimulation warrant the establishment of new safety guidelines/recommendations for the use of the technique among healthy volunteers, with additional cautionary requirements for its clinical translation.
An Ultrasonic Tool for Nerve Conduction Block in Diabetic Rat Models. [2019]Nerve conduction block with a high intensity-focused ultrasound (HIFU) transducer has been performed in normal and diabetic animal models recently. HIFU can reversibly block the conduction of peripheral nerves without damaging the nerves while using an appropriate ultrasonic parameter. Temporary and partial block of the action potentials of nerves shows that HIFU has the potential to be a useful clinical treatment for pain relief. This work demonstrates the procedures for suppressing the action potentials of neuropathic nerves in diabetic rats in vivo using an HIFU transducer. The first step is to generate adult male diabetic neuropathic rats by streptozotocin (STZ) injection. The second step is to evaluate the peripheral diabetic neuropathy in STZ-induced diabetic rats by an electronic von Frey probe and a hot plate. The final step is to record in vivo extracellular action potentials of the nerve exposed to HIFU sonication. The method showed here may benefit the study of ultrasound analgesic applications.
Evaluation of a Novel Acoustic Coupling Medium for Human Low-Intensity Focused Ultrasound Neuromodulation Applications. [2023]Single-element low-intensity focused ultrasound (LIFU) is an emerging form of human neuromodulation. Current coupling methods are impractical for clinical bedside use. Here, we evaluate commercially available high-viscosity gel polymer matrices as couplants for human LIFU neuromodulation applications.