Focused Ultrasound Neuromodulation for Treatment of Temporal Lobe Epilepsy

NCT03657056 | Withdrawn DMC FDA Device

• 1 other identifier: 2018P001352
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim of the proposed study is to assess the feasibility of using the BrainSonix BX Pulsar 1002 low-frequency and Low-Intensity Focused Ultrasound Pulsations (LIFUP) in human subjects suffering from intractable temporal lobe epilepsy. The patients selected will already be scheduled to undergo surgery for resection of the temporal lobe, and the investigational therapy will be applied to the temporal lobe at least one day prior to its scheduled removal. The study is intended to provide preliminary evidence of safety, and establish the feasibility of LIFUP treatment as evidenced by a modulation of the Blood-oxygenation level dependent (BOLD) signal in functional MRI (fMRI), and normal findings from histological examination of the resected brain tissue.

Conditions

Low Intensity Ultrasound Pulsarions

Keywords

Epilepsy; Ultrasound

Outcome Measures

Primary Outcomes (1)

• FMRI - (Change in BOLD signal)

  Change in BOLD signal during or after LIFUP sonication

  6 Months

Study Arms (1)

BX Pulsar 1002

EXPERIMENTAL

Low-Intensity Focused Ultrasound Pulsation (LIFUP) sonications will be conducted using the LIFUP experimental device BX Pulsar 1002 produced by the Brainsonix Corporation. For the purposes of safety LIFUP sonications will be initiated at the FDA limit for diagnostic ultrasound. However, the minimally effective dose in humans applications, according to (Lee et al., 2015), when derated is approximately 1125mW/cm2.

Device: BX Pulsar 1002

Interventions

BX Pulsar 1002 DEVICE

LIFUP will be administered to the temporal region on the side to undergo surgery, within the focus producing seizures. The ultrasound will be focused on the highest activity area within the temporal lobe. Functional MRI of the brain will be obtained throughout the LIFUP session. After the participant is fitted with the transducer they will be placed in the MRI machine and undergo a series of scans. After placing the transducer over the anterior tip of the temporal lobe the participant will undergo fMRI BOLD scans with LIFUP excitation (from (Lee et al., 2015): Tone Burst Duration = 2ms and Pulse Repetition Frequency = 250Hz) at four levels of intensity (720mW/cm2, 1440mW/cm2, 2880mW/cm2 and 5760mW/cm2). Before increasing the intensity, the transducer will be moved approximately 5mm posterior. After the last excitation scan the LIFUP parameters will be changed to inhibitory parameters (from (Yoo et al., 2011): Tone Burst Duration = 0.5ms and Pulse Repetition Frequency = 100Hz).

Also known as: LIFUP

BX Pulsar 1002

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female subjects, 18 to 60 years old.
• Subjects with clinical evidence from their diagnostic evaluations of unilateral hippocampal - dysfunction and epileptogenicity, confirmed via intracarotid amobarbital procedure (IAP) and neuropsychological testing.
• Subjects with seizures that have been refractory to treatment with at least three currently marketed antiepileptic drugs.
• Subjects currently taking antiepileptic medications.
• Subjects with at least 3 seizures/month based on seizure diary.
• Subjects with epilepsy who would clearly benefit from surgical intervention.
• Subjects who have been offered an anterior-mesial temporal lobe resection, performed en-bloc, as treatment for medication refractory epilepsy. This includes both dominant or non-dominant mesial temporal lobe focal epilepsy.

You may not qualify if:

• Subjects with a cognitive or psychiatric disorder that limits the ability to give informed consent or are unable to cooperate with the testing.
• Subjects with dementia, delirium and psychotic symptoms.
• Subjects with ferromagnetic materials in the head.
• Subjects with severe cardiac disease, increased intracranial pressure, or a transcutaneous electrical nerve stimulation (TENS) unit.
• Subjects who exhibit primary generalized seizures or pseudoseizures.
• Subjects who have seizures secondary to drugs, alcohol, metabolic illness or progressive degenerative disease.
• Subjects who have experienced status epilepticus during the 3-week period prior to the LIFUP procedure.
• Subjects (females) who are pregnant.
• Patients who have had electrodes implanted in the brain that were not explanted at least 6 weeks prior to the LIFUP procedure.
• Patients who have had electrodes implanted into the focal point of the temporal lobe that is proposed for the ultrasonic stimulation using LIFUP.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Related Publications (13)

• Hynynen K, Jolesz FA. Demonstration of potential noninvasive ultrasound brain therapy through an intact skull. Ultrasound Med Biol. 1998 Feb;24(2):275-83. doi: 10.1016/s0301-5629(97)00269-x.

  PMID: 9550186 BACKGROUND

• Gavrilov LR, Tsirulnikov EM, Davies IA. Application of focused ultrasound for the stimulation of neural structures. Ultrasound Med Biol. 1996;22(2):179-92. doi: 10.1016/0301-5629(96)83782-3.

  PMID: 8735528 BACKGROUND

• Tyler WJ, Tufail Y, Finsterwald M, Tauchmann ML, Olson EJ, Majestic C. Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound. PLoS One. 2008;3(10):e3511. doi: 10.1371/journal.pone.0003511. Epub 2008 Oct 29.

  PMID: 18958151 BACKGROUND

• Min BK, Bystritsky A, Jung KI, Fischer K, Zhang Y, Maeng LS, Park SI, Chung YA, Jolesz FA, Yoo SS. Focused ultrasound-mediated suppression of chemically-induced acute epileptic EEG activity. BMC Neurosci. 2011 Mar 6;12:23. doi: 10.1186/1471-2202-12-23.

  PMID: 21375781 BACKGROUND

• Yoo SS, Kim H, Min BK, Franck E, Park S. Transcranial focused ultrasound to the thalamus alters anesthesia time in rats. Neuroreport. 2011 Oct 26;22(15):783-7. doi: 10.1097/WNR.0b013e32834b2957.

  PMID: 21876461 BACKGROUND

• Deffieux T, Younan Y, Wattiez N, Tanter M, Pouget P, Aubry JF. Low-intensity focused ultrasound modulates monkey visuomotor behavior. Curr Biol. 2013 Dec 2;23(23):2430-3. doi: 10.1016/j.cub.2013.10.029. Epub 2013 Nov 14.

  PMID: 24239121 BACKGROUND

• Lee W, Kim H, Jung Y, Song IU, Chung YA, Yoo SS. Image-guided transcranial focused ultrasound stimulates human primary somatosensory cortex. Sci Rep. 2015 Mar 4;5:8743. doi: 10.1038/srep08743.

  PMID: 25735418 BACKGROUND

• Legon W, Sato TF, Opitz A, Mueller J, Barbour A, Williams A, Tyler WJ. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat Neurosci. 2014 Feb;17(2):322-9. doi: 10.1038/nn.3620. Epub 2014 Jan 12.

  PMID: 24413698 BACKGROUND

• Mitchell LA, Jackson GD, Kalnins RM, Saling MM, Fitt GJ, Ashpole RD, Berkovic SF. Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study. Neurology. 1999 Jan 15;52(2):327-36. doi: 10.1212/wnl.52.2.327.

  PMID: 9932952 BACKGROUND

• Vykhodtseva NI, Hynynen K, Damianou C. Histologic effects of high intensity pulsed ultrasound exposure with subharmonic emission in rabbit brain in vivo. Ultrasound Med Biol. 1995;21(7):969-79. doi: 10.1016/0301-5629(95)00038-s.

  PMID: 7491751 BACKGROUND

• Vykhodtseva N, McDannold N, Martin H, Bronson RT, Hynynen K. Apoptosis in ultrasound-produced threshold lesions in the rabbit brain. Ultrasound Med Biol. 2001 Jan;27(1):111-7. doi: 10.1016/s0301-5629(00)00275-1.

  PMID: 11295277 BACKGROUND

• Cohen MS, DuBois RM. Stability, repeatability, and the expression of signal magnitude in functional magnetic resonance imaging. J Magn Reson Imaging. 1999 Jul;10(1):33-40. doi: 10.1002/(sici)1522-2586(199907)10:13.0.co;2-n.

  PMID: 10398975 BACKGROUND

• Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23 Suppl 1:S208-19. doi: 10.1016/j.neuroimage.2004.07.051.

  PMID: 15501092 BACKGROUND

MeSH Terms

Conditions

Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Darin Dougherty, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Division of Neurotherapeutics, Department of Psychiatry

Model Details: Participants will be recruited from the normal population of patients being treated for temporal lobe epilepsy Massachusetts General Hospital. Patients identified as candidates for temporal lobe surgery by the clinical team will be notified via a letter that has been signed by a physician representative of the practice of their eligibility for the study. An administrator will follow-up on the letter with a phone call. The physician of potential participants will be notified of their eligibility for the study, and be provided with a copy of the consent form. A total of 3 participants will be enrolled in the project.

Study Record Dates

• First Submitted: August 30, 2018
• First Posted: September 4, 2018
• Study Start: January 1, 2022
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: March 16, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share