The Use of Focused Ultrasound and DCE K-trans Imaging to Evaluate Permeability of the Blood-Brain Barrier

NCT04063514 | Enrolling By Invitation

• 1 other identifier: ICSS-2018-001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The limitation of treating intrinsic brain pathologies has been circumvented with neurosurgical techniques; however, less invasive approaches may be desirable particularly for widespread or multifocal disease and when long term and repetitive administration is required. This study seeks to investigate the efficacy of focused ultrasound. Patients with either low grade gliomas or neurodegenerative dementias will be evaluated for study candidacy. There are no immediate benefits for patients who choose to participate; however, the information gained from this study will contribute to the research base and help patients in similar situations in the future.

Conditions

Low Grade Glioma of Brain

Outcome Measures

Primary Outcomes (2)

• Adverse Event (AE) & Serious Adverse Event (SAE) Reporting

  Per protocol, any suspected adverse events possibly related to the study protocol (e.g., itching, dizziness, headache, or neurological problems) will be tracked and monitored. In the event of a high-grade or serious adverse event, such event will be reported immediately and the study will be discontinued.

  24 hours

• functional Magnetic Resonance Imaging (fMRI)

  Some functional neuroimaging scans (e.g., high resolution T1-weighted images; Arterial Spin Labeling \[ASL\]; Dynamic Contrast Enhanced \[DCE\] perfusion sequences; post-contrast T1-weighted images, Susceptibility Weighted Imaging \[SWI\], T2 weighted imaging, and T2 Flair) will be used to evaluate longitudinal changes in perfusion as an efficacy measure. The scans will be acquired within one hour before and after the study procedures of focused transcranial ultrasound and infusion of definity microbubbles. Voxel-based comparisons showing perfusion values relative to the acquired data range will be used for quantification and comparison of baseline and post-procedure scans.

  3 hours

Study Arms (1)

Focused Ultrasound

EXPERIMENTAL

The ultrasound treatment will last either 1 hour or 20 minutes total time for the DWL device or Brainsonix Focused Ultrasound Device, respectively.

Other: Focused Ultrasound

Interventions

Focused Ultrasound OTHER

With focused ultrasound, there is an expected accentuation of local perfusion and potential temporary opening of the blood brain barrier with the aim is to provide better delivery of therapeutic agents including medication, particulates and cellular elements for treatment of neoplastic, inflammatory and degenerative brain diseases. The present study seeks to investigate differences in perfusion between areas treated and untreated by this modality in order to further explore its use in clinical application for the treatment of brain disease.

Focused Ultrasound

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects undergoing routine, repetitive MRI scanning for monitoring low grade gliomas
• or older

You may not qualify if:

• Cognitive decline with mild cognitive impairment (Clinical Dementia Rating stage 0.5) through moderate dementia CDR stages 1 and 2

Sponsors & Collaborators

• Neurological Associates of West Los Angeles: lead

Study Sites (1)

Neurological Associates of West LA

Santa Monica, California, 90403, United States

Location

Related Publications (11)

• McDannold N, Vykhodtseva N, Hynynen K. Targeted disruption of the blood-brain barrier with focused ultrasound: association with cavitation activity. Phys Med Biol. 2006 Feb 21;51(4):793-807. doi: 10.1088/0031-9155/51/4/003. Epub 2006 Jan 25.

  PMID: 16467579 BACKGROUND

• McDannold N, Vykhodtseva N, Hynynen K. Use of ultrasound pulses combined with Definity for targeted blood-brain barrier disruption: a feasibility study. Ultrasound Med Biol. 2007 Apr;33(4):584-90. doi: 10.1016/j.ultrasmedbio.2006.10.004.

  PMID: 17337109 BACKGROUND

• Hynynen K, McDannold N, Vykhodtseva N, Jolesz FA. Noninvasive MR imaging-guided focal opening of the blood-brain barrier in rabbits. Radiology. 2001 Sep;220(3):640-6. doi: 10.1148/radiol.2202001804.

  PMID: 11526261 BACKGROUND

• Hynynen K, McDannold N, Sheikov NA, Jolesz FA, Vykhodtseva N. Local and reversible blood-brain barrier disruption by noninvasive focused ultrasound at frequencies suitable for trans-skull sonications. Neuroimage. 2005 Jan 1;24(1):12-20. doi: 10.1016/j.neuroimage.2004.06.046.

  PMID: 15588592 BACKGROUND

• Hynynen K, McDannold N, Vykhodtseva N, Raymond S, Weissleder R, Jolesz FA, Sheikov N. Focal disruption of the blood-brain barrier due to 260-kHz ultrasound bursts: a method for molecular imaging and targeted drug delivery. J Neurosurg. 2006 Sep;105(3):445-54. doi: 10.3171/jns.2006.105.3.445.

  PMID: 16961141 BACKGROUND

• Treat LH, McDannold N, Vykhodtseva N, Zhang Y, Tam K, Hynynen K. Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI-guided focused ultrasound. Int J Cancer. 2007 Aug 15;121(4):901-7. doi: 10.1002/ijc.22732.

  PMID: 17437269 BACKGROUND

• Schlachetzki F, Holscher T, Koch HJ, Draganski B, May A, Schuierer G, Bogdahn U. Observation on the integrity of the blood-brain barrier after microbubble destruction by diagnostic transcranial color-coded sonography. J Ultrasound Med. 2002 Apr;21(4):419-29. doi: 10.7863/jum.2002.21.4.419.

  PMID: 11934099 BACKGROUND

• Yoshikawa K, Davies A. Safety of ProHance in special populations. Eur Radiol. 1997;7 Suppl 5:246-50. doi: 10.1007/pl00006901.

  PMID: 9370552 BACKGROUND

• Semelka RC, Ramalho J, Vakharia A, AlObaidy M, Burke LM, Jay M, Ramalho M. Gadolinium deposition disease: Initial description of a disease that has been around for a while. Magn Reson Imaging. 2016 Dec;34(10):1383-1390. doi: 10.1016/j.mri.2016.07.016. Epub 2016 Aug 13.

  PMID: 27530966 BACKGROUND

• Todd DJ, Kay J. Gadolinium-Induced Fibrosis. Annu Rev Med. 2016;67:273-91. doi: 10.1146/annurev-med-063014-124936.

  PMID: 26768242 BACKGROUND

• McDannold N, Vykhodtseva N, Raymond S, Jolesz FA, Hynynen K. MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits. Ultrasound Med Biol. 2005 Nov;31(11):1527-37. doi: 10.1016/j.ultrasmedbio.2005.07.010.

  PMID: 16286030 RESULT

Study Officials

• Sheldon Jordan, M.D.

  Neurologist, NAOWLA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 21, 2019
• Study Start: June 11, 2021
• Primary Completion: April 18, 2026
• Study Completion (Estimated): January 20, 2027
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

US (1)