Ultrasonic Debris Clearance to Promote Brain Resilience

Official title

Safety and Feasibility Trial of Ultrasonic Debris Clearance to Promote Brain Resilience

Overview

This pilot study will evaluate the safety, tolerability, and feasibility of Ultrasonic Debris Clearance (UDC), a noninvasive low-intensity focused ultrasound intervention, in amyloid-positive adults who are asymptomatic but at risk for Alzheimer's disease, or who have mild cognitive impairment or mild dementia. The study is designed to test whether repeated UDC sessions can be delivered safely and feasibly in this population, while also exploring efficacy via biomarkers and clinical measures.

Interventions

• Device Ultrasonic Debris Clearance
  Ultrasonic debris clearance (UDC) delivered with a 250-kHz low-intensity transcranial ultrasound device for approximately 30 minutes per session across 8 sessions over 4 weeks. The intervention is designed to provide broad transcranial ultrasound exposure to promote glymphatic clearance, with real-time monitoring of transmitted power and matched study procedures including EEG, MRI, blood, and clinical assessments.
• Device sham
  Sham procedure matched to the active UDC intervention in schedule, session duration, device setup, and study procedures, but without transcranial ultrasound energy delivery while maintaining participant blinding.

Primary outcome measures

• Number of Participants with Treatment-Related Adverse Events [Time frame: baseline through 2 months post-treatment initiation (up to 3 months)]

Secondary outcome measures (5)

• Changes from baseline in a tablet-based cognitive assessment [Time frame: baseline through 1 month post-treatment initiation (up to 3 months)]
• Changes from baseline in the CDR-SB [Time frame: baseline, 1 month post-treatment initiation (up to 3 months)]
• Changes from baseline in the ADASCog13 measure of cognition. [Time frame: baseline, 1 month post-treatment initiation (up to 3 months)]
• Changes from baseline in the ADCS-MCI-ADL [Time frame: baseline, 1 month post-treatment initiation (up to 3 months)]
• Changes from baseline in the Mini-Mental State Examination (MMSE) [Time frame: baseline, 1 month post-treatment initiation (up to 3 months)]

Eligibility criteria

Inclusion criteria

1.1. Physician-reported amyloid positivity diagnosed by amyloid positron emission tomography (PET) OR historic CSF positivity of Abeta42, total tau, or phosphorylated tau OR positivity of plasma pTau-217.

1.2. Age ≥ 18 years. No gender/sex, racial, or ethnic preference. Subjects greater than 60 years of age will be assumed to be non-pregnant based on age and expected post-menopausal status. Female subjects under the age of 60 will complete a two-step assessment of pregnancy status (a self-reported assessment of menopause that proceeds to a urine human chorionic gonadotropin (hCG) test to confirm non-pregnancy, if the participant is not post-menopausal).

1.3. CDR Scale score less than or equal to 1.0, consistent with mild, very mild, or no dementia.

1.4. Ability and willingness to comply with the study procedures (six sessions sitting in a procedure chair for up to one hour for the procedure, with an ultrasound device placed on their scalp; additional time for the MRI assessment, blood draws, and cognitive assessments).

1.5. Ability to understand and the willingness to sign a written informed consent document.

Exclusion criteria

2.1. Dementia of moderate or higher severity (CDR > 1.0) 2.2. Intracranial tumors, acute or chronic hemorrhage (beyond petechiae/microhemmorhage), or other current or historic central nervous system specific pathology. Baseline MRI studies will be screened by the protocol director to ensure no exclusionary intracranial pathology is present.

2.3. Any other comorbidity that would prevent adequate interpretation of the study results per the treatment team (e.g. congenital brain malformations without clinical importance) 2.4. Ultrasound attenuators along the ultrasound beam path (metal, air, or bulky calcification) including thick hair or related adornments that cannot be undone for the study (e.g. turbans, dreadlocks, hairweaves/wigs) that would prevent adequate ultrasound gel coupling of the device to the scalp or could trap air in the ultrasound beam path.

2.5. Contraindications to MRI (unknown device, claustrophobia) or metallic hardware in the head that prevent adequate MRI visualization of the brain 2.6. Allergy or similar intolerance to the materials used for ultrasound device coupling (ultrasound gel, silicone) 2.7. Receipt of anti-amyloid monoclonal antibody therapy within 6 months prior to screening 2.8. Moderate or greater depressive symptoms at screening, defined as a Patient Health Questionnaire-9 (PHQ-9) total score >= 10.

2.9. Clinically significant suicidal ideation or behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) 2.10. Clinically significant hematologic abnormalities, defined as hematocrit < 35% for male or < 32% for female, absolute neutrophil cell count < 1500/uL, absolute lymphocyte count < 900/uL, or platelet count < 120,000/uL 2.11. Clinically significant hepatic, renal, respiratory, cardiovascular, or metabolic disease that increases risk or interferes with interpretation, defined as ALT/AST/ALP > 1.5 ULN, or eGFR < 50 mL/min/1.73m2, or recent MI/unstable angina/HF/cardiomyopathy within 6 months, 2.12. Significant bradycardia(<50/min) or tachycardia (>100/min) 2.13. Poorly controlled BP 2.14. Uncontrolled diabetes, defined as HbA1c > 7.5 2.15. Active clinically significant infection or other systemic illness affecting the CNS

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Other

Study locations

United States · 1 center

• Stanford University — Stanford

Identifiers

NCT: NCT07573982 · 85009

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗