Ultrasound Brain Stimulation for Anesthetic Sedation

Overseen By Amy McKinney

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Michigan

Disqualifiers: Pregnancy, Cardiopulmonary disease, Neurological illness, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how mental functions operate under varying levels of anesthesia and whether ultrasound brain stimulation aids in faster recovery from anesthesia. Researchers will divide participants into groups, each receiving stimulation in different brain areas or a sham treatment. This study may suit right-handed, English-speaking adults with a Body Mass Index (BMI) below 30. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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, you must abstain from alcohol for 24 hours before the study and have a negative drug screen.

What prior data suggests that ultrasonic deep brain stimulation is safe for use during anesthesia?

Research shows that using ultrasound on the brain is generally safe. Studies have found no signs of brain damage or harm to the blood-brain barrier, which protects the brain from harmful substances. The FDA considers some related studies "low risk," indicating minimal risk. While any procedure carries some risk, ultrasound on the brain has a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using ultrasonic deep brain stimulation for anesthetic sedation because it offers a non-invasive way to influence brain activity. Unlike traditional sedatives that work systemically and can have widespread effects on the body, this method targets specific brain areas like the anterior insula cortex, central thalamus, and dorsolateral prefrontal cortex. By focusing on these precise regions, it aims to provide more controlled sedation with potentially fewer side effects. Additionally, the use of ultrasound technology means this technique could allow for adjustable sedation levels and quicker recovery times compared to conventional methods.

What evidence suggests that ultrasonic deep brain stimulation is effective for accelerating return to consciousness during anesthesia?

Research shows that using ultrasound on the brain can help people wake up faster from anesthesia. In studies with mice, low-intensity ultrasound made them regain consciousness more quickly. Reports have not indicated any harm from this method, suggesting it is safe. In this trial, participants will receive Ultrasonic Deep Brain Stimulation targeting different brain areas, such as the anterior insula cortex, central thalamus, or dorsolateral prefrontal cortex, to evaluate its effectiveness in aiding recovery from sedation. Deep brain stimulation already treats conditions like Parkinson's disease successfully, indicating its potential usefulness in other areas. These findings suggest it could help patients wake up more quickly after sedation. ^{1 5 6 7 8}

Who Is on the Research Team?

Zirui Huang

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for right-handed, English-speaking adults with a BMI under 30. It's not for those who can't have an MRI due to medical reasons, pregnancy, breastfeeding, certain tattoos, or metal in the body. People with learning disabilities, sleep apnea, GERD, recent food intake (within 8 hours), allergies to propofol/eggs/soy products or history of substance abuse are also excluded.

Inclusion Criteria

All subjects will be English speakers

I am right-handed and an adult.

Body mass index (BMI) less than 30

Exclusion Criteria

BMI>30

Participants will be excluded if they have any medical contraindication to MRI scanning

Intracranial structural abnormality on T1-weighted MRI scans

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Anesthetic Sedation and Ultrasonic Stimulation

Participants undergo different levels of anesthesia and receive ultrasonic brain stimulation to evaluate mental functions and return to consciousness

Up to 90 minutes

Follow-up

Participants are monitored for safety and effectiveness after the procedure

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Functional Magnetic Resonance Imaging (fMRI) using Propofol
• Ultrasonic Deep Brain Stimulation

Trial Overview

The study tests if ultrasonic brain stimulation (LIFUP) during anesthesia affects mental functions and speeds up waking up. Participants will undergo fMRI scans while receiving different levels of sedation with Propofol to monitor their brain activity.

How Is the Trial Designed?

Group I: Dorsolateral prefrontal cortex (DLPFC) Experimental Treatment 2 Interventions

Group II: Central thalamus (CT) Experimental Treatment 2 Interventions

Group III: Anterior insula cortex (AIC) Experimental Treatment 2 Interventions

Group IV: Sham control Active Control 1 Intervention

Ultrasonic Deep Brain Stimulation is already approved in United States, European Union for the following indications:

Approved in United States as Ultrasonic DBS for:

• Research purposes for neurological conditions such as Parkinson's disease, essential tremor, and epilepsy

Approved in European Union as Focused Ultrasound Deep Brain Stimulation for:

• Research purposes for neurological conditions such as Parkinson's disease, essential tremor, and epilepsy

Who Is Running the Clinical Trial?

University of Michigan

Lead Sponsor

Trials

1,891

Recruited

6,458,000+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Published Research Related to This Trial

A new miniaturized ultrasound ring array transducer has been developed, weighing only 0.035 g, which allows for neuromodulation in freely-moving awake mice, overcoming limitations of previous bulky devices.

This innovative transducer successfully induced motor responses in both affixed and awake states, enabling a wider range of in vivo experiments in neuroscience research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Miniature ultrasound ring array transducers for transcranial ultrasound neuromodulation of freely-moving small animals. Kim, H., Kim, S., Sim, NS., et al.[2019]

Using focused ultrasound to temporarily open the blood-brain barrier in non-human primates allows for effective delivery of GABA, leading to a significant decrease in visual cortex activity in a dose-dependent manner.

The study demonstrated that the GABA-induced inhibition was much more effective than the effects of ultrasound alone, highlighting the potential of this method for non-invasive brain modulation while ensuring safety through monitoring cavitation levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive ultrasonic modulation of visual evoked response by GABA delivery through the blood brain barrier. Constans, C., Ahnine, H., Santin, M., et al.[2021]

Transcranial ultrasound stimulation (TUS) can non-invasively target both cortical and deep brain structures with high spatial resolution, potentially allowing for precise neuromodulation that was previously only possible with invasive methods.

The mechanism of TUS involves ultrasound waves interacting with neuronal membranes, leading to changes in neuronal excitability, which could have significant implications for both basic research and clinical applications in neuromodulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive transcranial ultrasound stimulation for neuromodulation. Darmani, G., Bergmann, TO., Butts Pauly, K., et al.[2022]

Transcranial focused ultrasound (FUS) applied to the thalamus of anesthetized rats significantly reduced the time it took for them to regain voluntary movement after anesthesia, indicating its potential for neuromodulation.

The study suggests that FUS could have therapeutic applications for disorders of consciousness, such as minimally conscious states, by altering brain tissue excitability noninvasively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound to the thalamus alters anesthesia time in rats. Yoo, SS., Kim, H., Min, BK., et al.[2022]

Transcranial focused ultrasound (FUS) successfully stimulated the primary visual cortex in humans, activating not only the targeted area but also related brain regions involved in visual and cognitive processes, as confirmed by functional MRI.

No adverse effects were reported in participants, indicating that FUS is a safe method for non-invasive brain stimulation, with potential applications in neuroscience and therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial focused ultrasound stimulation of human primary visual cortex. Lee, W., Kim, HC., Jung, Y., et al.[2022]

Low-intensity transcranial focused ultrasound (tFUS) can effectively stimulate brain areas in awake sheep, showing that it can produce significant motor responses with high spatial resolution, particularly when using shorter pulse durations (0.5 and 1 ms) which resulted in stronger electromyography (EMG) signals.

The study demonstrated that tFUS is safe for use in awake animals, as no abnormalities were observed in behavioral assessments or histological analyses conducted 24 hours and one month after stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of focused ultrasound pulse duration on stimulating cortical and subcortical motor circuits in awake sheep. Kim, HC., Lee, W., Kowsari, K., et al.[2023]

Researchers have created biodegradable nanoparticles that can noninvasively release the anesthetic propofol in the brain using focused ultrasound, which could change how we approach brain treatments.

In tests on rats, these nanoparticles effectively silenced seizures without causing any damage to brain tissue or disrupting the blood-brain barrier, indicating a safe method for neuromodulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Targeted Transcranial Neuromodulation via Focused Ultrasound Gated Drug Release from Nanoemulsions. Airan, RD., Meyer, RA., Ellens, NP., et al.[2022]

Transcranial focused ultrasound (tFUS) can precisely target specific brain areas with low acoustic intensity, effectively modulating brain excitability and potentially promoting neural plasticity for neurorehabilitation.

The review highlights the excellent safety profile of tFUS, but emphasizes the need for new safety guidelines and recommendations for its use in healthy volunteers and clinical settings, based on a comprehensive analysis of acoustic parameters and their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review and Perspectives of Transcranial Focused Ultrasound Brain Stimulation. Lee, W., Weisholtz, DS., Strangman, GE., et al.[2023]

Low-intensity transcranial ultrasound stimulation (TUS) significantly reduced the time to emerge from propofol anaesthesia in mice, with an average recovery time of 20.3 minutes compared to 32 minutes in the control group.

TUS altered neural activity by changing the power and entropy of local field potentials in specific frequency bands, indicating its potential to modulate brain function during anaesthesia recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity transcranial ultrasound stimulation modulates neural activities in mice under propofol anaesthesia. Liu, M., Yuan, Y., Wang, X., et al.[2023]

Ultrasonic neuromodulation is a promising non-invasive method for brain stimulation, effectively targeting the hippocampus with 85.65% of the ultrasound energy delivered to this specific area using customized transducers.

The study found that variations in transducer position had minimal impact on energy delivery, indicating that this technique could be reliably applied in clinical settings, with sound speed being the most critical factor affecting the ultrasound's effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Numerical investigation of the energy distribution of Low-intensity transcranial focused ultrasound neuromodulation for hippocampus. Huang, Y., Wen, P., Song, B., et al.[2022]

Focused transcranial ultrasound stimulation (TUS) can effectively modulate activity in deep brain areas, such as the amygdala and anterior cingulate cortex, in macaques, demonstrating its potential as a tool for studying neural networks.

The study used functional magnetic resonance imaging (fMRI) to show that TUS reduces the connectivity between the targeted brain areas and the rest of the brain, indicating specific and localized effects of the stimulation without being influenced by auditory confounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Manipulation of Subcortical and Deep Cortical Activity in the Primate Brain Using Transcranial Focused Ultrasound Stimulation. Folloni, D., Verhagen, L., Mars, RB., et al.[2022]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07221539

Restoration of Consciousness With Ultrasonic Deep Brain ...

The purpose of this study is to see if mental functions take place during different levels of anesthesia using two commonly used drug (propofol and ...

2.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/45/NCT05495945/Prot_SAP_000.pdf

Ultrasonic Deep Brain Stimulation During Anesthetic ...

The majority of studies with ultrasound have reported no adverse events or evidence of anatomical damage [32,44–47].

3.

withpower.com

withpower.com/trial/phase-2-mental-function-7-2022-abd55

Ultrasound Brain Stimulation for Anesthetic Sedation

Low-intensity transcranial ultrasound stimulation (TUS) significantly reduced the time to emerge from propofol anaesthesia in mice, with an average recovery ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12063574/

High Intensity Focused Ultrasound – Longitudinal Data on ...

Despite this, results were similar in demonstrating that tremor control in DBS was superior to that in HiFU, with 80% vs 68% improvement in ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S000709121734000X

Anaesthesia for deep brain stimulation and in patients with ...

In particular, deep brain stimulation (DBS) is now an effective treatment for Parkinson's disease. Thalamic DBS was first developed for tremor control.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4158643/

Anesthetic Challenges for Deep Brain Stimulation

This review highlights the focus on the recent development in the anesthetic management and the effects of anesthetic technique on DBS.

7.

mayoclinic.org

mayoclinic.org/tests-procedures/deep-brain-stimulation/about/pac-20384562

Deep brain stimulation

Risks. Deep brain stimulation is generally considered to be low risk. But any type of surgery has the risk of complications. Also, brain ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S1935861X19303389

Safety of transcranial focused ultrasound stimulation

At high stimulation intensity and/or rate, TFUS may cause haemorrhage, cell death or damage, and unintentional blood-brain barrier (BBB) opening. TFUS may also ...