Table 1.
A summary of clinical trials to date evaluating the effects of ultrasound-mediated blood–brain barrier opening in humans (ClinicalTrials.gov, 2021). GBM, Glioblastoma multiforme; MRgFUS, MR-guided Focused; US, ultrasound. Permission for adaptation from ref [211] granted under Creative Commons Attribution 4.0 International License, (http://creativecommons.org/licenses/by/4.0/; accessed on 28 June 2022).
| Trial Number | Study Title, Date | Condition | Interventions | Number of Participants | Therapeutic Protocol | Location | Status | |
|---|---|---|---|---|---|---|---|---|
| Brain tumours | ||||||||
| 1 | NCT02253212 | Safety of BBB Opening With the SonoCloud (SONOCLOUD), 2014 | Glioma or GBM | Device: SonoCloud® Drug: Carboplatin and SonoVue® microbubble |
27 | The US (0.5–1.1 Mpa) was activated monthly before IV administration of carboplatin and microbbuble (0.1 mL/kg) (min. 6 cycles) [83]. | France | Completed |
| 2 | NCT02343991 | Blood–Brain Barrier Disruption Using Transcranial MRI-Guided Focused US, 2014 | Primary brain tumours | Device: ExAblate MRgFUS Drug: Liposomal doxorubicin or Temozolomide with Definity® microbubbles |
10 | Five patients underwent the MRgFUS in conjunction with administration of chemotherapy (n = 1 liposomal doxorubicin, n = 4 temozolomide) one day prior to surgical resection. Samples of “sonicated” and “unsonicated” tissue were collected during surgery [242]. | Canada | Active, not recruiting |
| 3 | NCT03712293 | ExAblate Blood–Brain Barrier Disruption for Glioblastoma in Patients Undergoing Standard Chemotherapy, 2018 | GBM | Device: Transcranial ExAblate 4000 Type 2.0 MRgFUS Drug: Temozolomide |
10 | The ExAblate BBB disruption will coincide with one of three first days of each planned temozolomide adjuvant therapy cycle as one procedure per cycle. | South Korea | Recruiting |
| 4 | NCT03626896 | Safety of BBB Disruption Using NaviFUS System in Recurrent Glioblastoma Multiforme (GBM) Patients, 2018 | Glioma or GBM | Device: NaviFUS® System Drug: None. |
6 | The study will be carried out in patients with recurrent GBM who will undergo surgery within 2 weeks to evaluate the safety and the tolerated US dose (escalated exposure average 10–16 W). | Taiwan | Completed |
| 5 | NCT03616860 | Assessment of Safety and Feasibility of ExAblate Blood–Brain Barrier (BBB) Disruption for Treatment of Glioma, 2018 | GBM | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Temozolomide and Definity® microbubbles |
20 | Patients will undergo up to 6 treatments with FUS coincident with their standard temozolomide cycles. | Canada | Recruiting |
| 6 | NCT03714243 | Blood–Brain Barrier Disruption (BBBD) Using MRgFUS in the Treatment of Her2-positive Breast Cancer Brain Metastases (BBBD), 2019 | Metastatic HER-2 positive breast cancer | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Trastuzumab |
10 | Six study ExAblate BBB opening treatment cycles, every 2–3 weeks based on their trastuzumab regimen. | Canada | Recruiting |
| 7 | NCT03744026 | Safety and Efficacy of Transient Opening of the Blood–Brain Barrier (BBB) With the SonoCloud-9 (SC9-GBM-01), 2019 | GBM | Device: SonoCloud-9 Drug: Carboplatin |
33 | Patients will undergo 6 cycles of carboplatin treatments every 4 weeks coincident with BBB opening in resection area and surrounding tissues using SonoCloud-9 system [238]. | France | Recruiting |
| 8 | NCT03551249 | Assessment of Safety and Feasibility of ExAblate Blood–Brain Barrier (BBB) Disruption, 2019 | Glioma or GBM | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Temozolomide |
20 | BBB will be disturbed along the periphery of tumour resection cavity prior to beginning the planned adjuvant temozolomide chemotherapy phase of treatment. | USA | Recruiting |
| 9 | NCT04021420 | Safety and Efficacy of Sonocloud Device Combined With Nivolumab in Brain Metastases From Patients With Melanoma (SONIMEL01), 2019 | Metastatic melanoma | Device: SonoCloud®
Drug: Nivolumab Injection alone or with Ipilimumab |
21 | Along with systemic injection of an US resonator and prior to beginning the chemo-treatment, SonoCloud® delivers US for a duration of 120–270 s. A total of 3 US dose levels will be evaluated (0.78, 0.9 and 1.03 MPa). | France | Recruiting |
| 10 | NCT04528680 | US-based Blood–Brain Barrier Opening and Albumin-bound Paclitaxel for Recurrent Glioblastoma (SC9/ABX), 2020 | GBM | Device: SonoCloud-9 Drug: Albumin-bound paclitaxel (Abraxane®), microbubbles |
39 | The device will be implanted at the time of surgical resection of the recurrent tumour. During that procedure, a first test dose of the chemotherapy will be administered in the operating room after sonication and tissue concentrations in different parts of the resected tumour will be measured. In select patients, the sonication procedure will occur immediately after the test dose of chemotherapy is administered. | USA | Recruiting |
| 11 | NCT04614493 | Innovative SonoCloud-9 Device for Blood–Brain Barrier Opening in First Line Temozolomide Glioblastoma Patients. (SonoFIRST), 2020 | GBM | Device: SonoCloud-9 Drug: Temozolomide |
66 | The patients will receive daily temozolomide during Radiation, followed by 6 months of adjuvant temozolomide 5 days/months) with 6 concomitant BBB opening sessions by US + 9 BBB opening sessions by US without any associated drug. | Belgium/France | Not yet recruiting |
| 12 | NCT04440358 | ExAblate Blood–Brain Barrier Disruption With Carboplatin for the Treatment of rGBM, 2020 | GBM | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Carboplatin with microbubble |
50 | Patients will undergo up to 6 cycles of ExAblate BBBD procedures in conjunction with carboplatin chemotherapy about every 4 weeks. | South Korea | Recruiting |
| 13 | NCT04417088 | ExAblate Blood–Brain Barrier Disruption for the Treatment of rGBM in Subjects Undergoing Carboplatin Monotherapy, 2020 | GBM | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Carboplatin with microbubble |
30 | Patients will undergo up to 6 cycles of ExAblate BBBD procedures in conjunction with carboplatin chemotherapy about every 4 weeks. | USA | Recruiting |
| 14 | NCT04804709 | Non-Invasive Focused US (FUS) With Oral Panobinostat in Children With Progressive Diffuse Midline Glioma (DMG), 2021 | Diffuse Midline Glioma | Device: FUS treatment with neuro-navigator-controlled sonication Drug: Panobinostat, microbubbles |
15 | After each instance of opening the BBB using specific parameters of FUS in the specific number of tumour sites (one, two, or three), the subjects will receive oral Panobinostat. | USA | Recruiting |
| 15 | NCT04063514 | The Use of Focused US and DCE K-trans Imaging to Evaluate Permeability of the Blood–Brain Barrier, 2025 | Glioma | Device: Brainsonix FUS and DWL Doppler system Drug: Definity® microbubbles |
15 | Not mentioned. | USA | Not yet recruiting |
| Alzheimer’s Disease | ||||||||
| 1 | NCT02986932 | Blood–Brain Barrier Opening Using Focused US With IV Contrast Agents in Patients With Early Alzheimer’s Disease (BBB-Alzheimers), 2016 | Alzheimer’s Disease | Device: ExAblate MRgFUS Drug: Definity® microbubbles |
6 | In the first stage, patients will undergo a small area BBB opening (9 × 9 mm) with multiple sonications to establish the minimum required sonication parameters. In stage II, a larger volume (2.5–3.0 cm) will be targeted. | Canada | Completed |
| 2 | NCT03119961 | Blood–Brain Barrier Opening in Alzheimer’s Disease (BOREAL1), 2017 | Alzheimer’s Disease | Device: SonoCloud®, CarThéra Drug: anti- Alzheimer’s Disease drugs |
10 | Not mentioned. | France | Completed |
| 3 | NCT03671889 | ExAblate Blood–Brain Barrier (BBB) Disruption for the Treatment of Alzheimer’s Disease, 2018 | Alzheimer’s Disease | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Not mentioned |
20 | Three serial ExAblate BBB disruption procedures in specific areas in the brain will be carried out. | USA | Recruiting |
| 4 | NCT03739905 | ExAblate Blood–Brain Barrier Opening for Treatment of Alzheimer’s Disease, 2018 | Alzheimer’s Disease | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Alzheimer’s medication |
30 | Three serial ExAblate BBB disruption procedures in specific areas in the brain will be carried out. | Canada | Recruiting |
| 5 | NCT04118764 | Non-invasive Blood–Brain Barrier Opening in Alzheimer’s Disease Patients Using Focused US, 2020 | Alzheimer’s Disease | Device: Neuronavigation-guided single-element focused US transducer Drug: Definity® microbubbles |
6 | Patients will undergo a FUS treatment to the brain, along with Magnetic Resonance Imagine [128] with or without gadolinium contrast agents and Positron Emission Tomography (PET) scans. | USA | Recruiting |
| 6 | NCT04526262 | Assessment of Initial Efficacy and Safety of High Intensity Focused US ‘ExAblate 4000 Type 2′ for Blood–Brain Barrier Disruption in Patients With Alzheimer’s Disease, 2020 | Alzheimer’s Disease | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Alzheimer’s medication |
6 | Two sessions of transcranial magnetic resonance-guided focused US blood–brain barrier disruption every 3 months. | South Korea | Active, not recruiting |
| Other | ||||||||
| 1 | NCT03608553 | A Study to Evaluate Temporary Blood–Brain Barrier Disruption in Patients With Parkinson’s Disease Dementia, 2018 | Parkinson’s Disease with dementia | Device: ExAblate 4000 Type 2.0 MRgFUS Drug: Luminity® |
10 | In the first stage, patients will undergo a small area BBB opening (9 × 9 mm) with multiple sonications to establish the minimum required sonication parameters. In stage II, a larger volume (2.5–3.0 cm) will be targeted. | Spain | Active, not recruiting |
| 2 | NCT03321487 | Blood–Brain Barrier Opening Using MR-Guided Focused US in Patients With Amyotrophic Lateral Sclerosis, 2018 | Amyotrophic Lateral Sclerosis (ALS) | Device: ExAblate MRgFUS Drug: None |
8 | BBB will be disturbed using US in conjunction with an intravenous US contrast agent. | Canada | Active, not recruiting |
| 3 | NCT04370665 | Blood–Brain Barrier Disruption With Cerezyme in Patients With Parkinson’s Disease, 2020 | Parkinson’s Disease | Device: ExAblate MRgFUS Drug: Cerezyme® (an analogue of the human enzyme beta-glucocerebrosidase) |
4 | Patients will undergo three biweekly delivery of Cerezyme® via MRgFUS induced BBB opening to unilateral putamen. | Canada | Active, not recruiting |