NCT05983575 — A Pivotal Study of LIPUS-Brain in Patients With Early Alzheimer's Disease
| Field |
Value |
| Phase |
Phase 3 |
| Status |
Active, not recruiting |
| Enrollment |
220 participants (estimated) |
| Sponsor |
Sound Wave Innovation CO., LTD. |
| Study Type |
Interventional |
| Design |
Randomized, double-blind, placebo-controlled |
| Start Date |
October 31, 2023 |
| Primary Completion |
January 31, 2026 (estimated) |
| Completion |
July 31, 2026 (estimated) |
This is a multicenter, randomized, double-blinded, placebo-controlled Phase 3 study comparing LIPUS-Brain transcranial low-intensity pulsed-wave ultrasound device to placebo in patients with early Alzheimer's disease. The primary objective is to assess changes in ADAS-J-cog-14 scores from baseline to 72 weeks.
LIPUS-Brain delivers transcranial low-intensity pulsed-wave ultrasound to the brain. The mechanism is believed to involve:
- Neuromodulation: Ultrasound waves modulate neuronal activity
- Blood-brain barrier modulation: May temporarily increase blood-brain barrier permeability
- Neuroprotective effects: May promote neurogenesis and synaptic plasticity
¶ Arms and Interventions
| Arm |
Intervention |
| Experimental |
LIPUS-Brain (transcranial low-power pulsed-wave ultrasound device) |
| Placebo comparator |
Placebo device |
- Patients aged 50-89 years
- Mild AD or MCI due to AD per NIA/AA 2018 diagnostic criteria
- Amyloid PET positive
- CDR global score 0.5 (MCI) to 1.0 (Mild AD)
- MMSE-J score ≥20 at screening
- Stable AD medication for ≥4 weeks
- Symptomatic cerebral hemorrhage/infarction within 48 weeks
- Modified Hachinski Ischemic Scale score ≥5
- Lewy body dementia or frontotemporal dementia
- Implants such as coils, electrodes, stents in skull
- Brain surgery within 5 years
- Epilepsy history
- ADAS-J-cog-14 change from baseline to Week 72
- ADAS-J-cog-14 change at Weeks 24 and 48
- CDR-SB change at Weeks 48 and 72
- NPIQ-J ( Neuropsychiatric Inventory-Questionnaire Japanese)
- J-ZBI (Japanese version of Zarit Burden Interview)
- WMS-R (Wechsler Memory Scale-Revised)
- MMSE-J (Japanese MMSE)
- FAQ (Functional Activities Questionnaire)
- EQ-5D-5L quality of life
- ABC Dementia scale
- Response rate (% with no deterioration or improvement in ADAS-J-cog-14)
- Transition rate from MCI due to AD to AD
- Nagoya University Hospital (Nagoya)
- National Center for Geriatrics and Gerontology (Obu)
- IUHW Narita Hospital (Narita)
- Fukuoka Sanno Hospital (Fukuoka)
- Sapporo Medical University Hospital (Sapporo)
- Kanazawa University Hospital (Kanazawa)
- Tohoku University Hospital (Sendai)
- Niigata University Medical and Dental Hospital (Niigata)
- Kansai Medical University Hospital (Hirakata)
- National Cerebral and Cardiovascular Center (Suita)
- Juntendo University Hospital (Tokyo)
- The University of Tokyo Hospital (Tokyo)
- Tokyo Metropolitan Geriatrics Hospital (Tokyo)
¶ Rationale and Design
The trial rationale and design were published by Shimokawa et al. in J Alzheimers Dis Rep 2025. The baseline characteristics of enrolled patients were subsequently reported in J Alzheimers Dis Rep 2025.
- Shimokawa et al., Baseline characteristics of patients with early Alzheimer's disease enrolled in the pivotal trial of low-intensity pulsed ultrasound (LIPUS-AD). J Alzheimers Dis Rep (2025)
- Shimokawa et al., Pivotal trial of low-intensity pulsed ultrasound therapy for early Alzheimer's disease: Rationale and design. J Alzheimers Dis Rep (2025)