lipus-brain-phase-3-ad-nct05983575

Trial Overview

NCT05983575 — A Pivotal Study of LIPUS-Brain in Patients With Early Alzheimer's Disease

Key Information

| 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) |

Trial Overview

NCT05983575 — A Pivotal Study of LIPUS-Brain in Patients With Early Alzheimer's Disease

Key Information

| 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) |

Study Description

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.

Mechanism of Action

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 |

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Outcome Measures

Primary Outcomes

• ADAS-J-cog-14 change from baseline to Week 72

Secondary Outcomes

• 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

Study Sites (Japan)

• 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](https://pubmed.ncbi.nlm.nih.gov/40034530/). The baseline characteristics of enrolled patients were subsequently reported in [J Alzheimers Dis Rep 2025](https://pubmed.ncbi.nlm.nih.gov/41477670/).

Related Pages

• [Focused Ultrasound](/therapeutics/focused-ultrasound) — Overview of focused ultrasound therapeutic applications
• [Alzheimer's Disease Clinical Trials](/clinical-trials/alzheimers-disease) — Index of AD trials
• [Non-Pharmacological Therapies](/therapeutics/non-pharmacological-therapies-alzheimer) — Other non-pharmacological approaches

References