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

NCT05983575 | Active Not Recruiting Phase 3

• 1 other identifier: LB1101
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 19

Brief Summary

This study 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 of the study is to assess changes in ADAS-J-cog-14 scores from baseline to 72 weeks.

Conditions

Alzheimer Disease, Early Onset

Outcome Measures

Primary Outcomes (1)

• Changes in ADAS-J-cog-14 scores from baseline to Week 72

  Performed at Week 72

Secondary Outcomes (13)

• Changes in ADAS-J-cog-14 scores from baseline to Week 24 and 48

  Performed at Week 24 and 48

• Changes in CDR-SB from baseline to Week 48 and 72

  Performed at Week 48 and 72

• Changes in NPIQ-J scores from baseline to Week 24, 48 and 72

  Performed at Week 24, 48 and 72

• Changes in J-ZBI scores from baseline to Week 24, 48 and 72

  Performed at Week 24, 48 and 72

• Changes in WMS-R scores from baseline to Week 24, 48 and 72

  Performed at Week 24, 48 and 72

Study Arms (2)

LIPUS-Brain

EXPERIMENTAL

Device: LIPUS-Brain

Placebo

PLACEBO COMPARATOR

Device: Placebo

Interventions

LIPUS-Brain DEVICE

Transcranial low-power pulsed-wave ultrasound device

LIPUS-Brain

Placebo DEVICE

Placebo

Placebo

Eligibility Criteria

• Age: 50 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written informed consent to participate in the clinical trial from the patient and their legal representative.
• Mild AD or MCI due to AD patient aged greater than or equal to (\>=) 50 and less than (\<) 90 years, at the time of informed consent.
• Patients with the same partner/informant who meet all of the following conditions during the study period
• Living with or in contact with the patient
• It is possible to observe the patient's activities of daily living and physical condition.
• Being able to be present at all times during the efficacy evaluation specified in this clinical trial
• Person judged by an investigator to be able to manage administration of concomitant medications
• Patients who met the diagnostic criteria of Mild AD or MCI due to AD according to the NIA/AA 2018 diagnostic criteria at the time of informed consent and were diagnosed as positive by the amyloid PET imaging evaluation committee.
• Have a CDR global score of 0.5 (MCI due to AD) to 1.0 (Mild AD) at screening.
• Patients with her MMSE-J score \>=20 at screening.
• No organic diseases such as symptomatic cerebral hemorrhage, symptomatic cerebral infarction, acute cerebral infarction, brain tumor, etc. within 48 weeks before obtaining informed consent or in head MRI images at screening, and in head MRA images, Patients evaluated by the imaging evaluation committee as not having severe stenosis/occlusion from the internal carotid artery to the middle cerebral artery.
• Patients who are receiving existing drug therapy for Mild AD or MCI due to AD and are not scheduled to change their medication within the past 4 weeks from obtaining consent and after obtaining consent.

You may not qualify if:

• Patients judged by the investigator that it is difficult to continue the study treatment for 20 minutes.
• Patients judged by the investigator to be difficult to perform an MRI examination.
• Patients with impaired consciousness with a GCS score of 12 or less at the time of enrollment.
• Patients who have had symptomatic cerebral infarction or cerebral hemorrhage within 12 weeks prior to enrollment.
• Patients with a modified Hachinski Ischemic Scale score of 5 or more at enrollment.
• Patients with Lewy body dementia and frontotemporal dementia.
• Patients judged by the investigator to be difficult to participate in the clinical trial due to severe mental illness
• Poorly controlled serious systemic disease (heart failure, liver failure, renal failure, vitamin B12 deficiency, hypothyroidism, etc.) that makes it difficult for the investigator to participate in the study judged patient.
• Patients with uncontrolled diabetic retinopathy (with active fundus hemorrhage).
• Patients who have malignant tumor as a complication or who have been treated for malignant tumor within 5 years from the time of enrollment (excluding cured resected carcinoma in situ).
• Patients who are or have a history of drug addiction or alcohol addiction.
• Patients with or with a history of epilepsy.
• Patients with implants such as coils, electrodes and stents in the skull.
• Patients within 5 years after brain surgery (including endovascular treatment).
• Patients who are pregnant or wish to become pregnant.

Sponsors & Collaborators

• Sound Wave Innovation CO., LTD.: lead

Study Sites (19)

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

National Center for Geriatrics and Gerontology

Ōbu, Aichi-ken, 474-8511, Japan

Location

IUHW Narita Hospital

Narita, Chiba, 286-8520, Japan

Location

Fukuoka Sanno Hospital

Fukuoka, Fukuoka, 814-0001, Japan

Location

Imon Yukari Neurology Clinic

Hiroshima, Hiroshima, 732-0066, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Memory Clinic Toride

Toride, Ibaragi, 302-0004, Japan

Location

Kanazawa University Hospital

Kanazawa, Ishikawa-ken, 920-8641, Japan

Location

Tohoku University Hospital

Sendai, Miyagi, 980-8574, Japan

Location

Niigata University Medical and Dental Hospital

Niigata, Niigata, 951-8122, Japan

Location

KATAYAMA medical Clinic

Kurashiki, Okayama-ken, 710-0813, Japan

Location

Kansai Medical University Hospital

Hirakata, Osaka, 573-1191, Japan

Location

National Cerebral and Cardiovascular Center

Suita, Osaka, 564-8565, Japan

Location

International University of Health and welfare Hospital

Nasushiobara, Tochigi, 329-2763, Japan

Location

Juntendo University School of Medicine Juntendo Hospital

Bunkyō-Ku, Tokyo, 113-0033, Japan

Location

Memory Clinic Ochanomizu

Bunkyō-Ku, Tokyo, 113-0034, Japan

Location

The University of Tokyo Hospital

Bunkyō-Ku, Tokyo, 113-8655, Japan

Location

Tokyo Metropolitan Geriatrics Hospital

Itabashi-ku, Tokyo, 173-0015, Japan

Location

Tottori University Hospital

Yonago, Tottori, 683-8504, Japan

Location

Related Publications (2)

• Shimokawa H, Akishita M, Asada T, Katayama S, Hattori Y, Yakushiji Y, Taki Y, Murai H, Boku Y, Tsujimoto M, Umegaki H, Ogawa T, Matsumoto S, Ono K, Imon Y, Tsunemi T, Iwata A, Hanajima R, Hisahara S, Uehara T, Ishiguro T, Nakaoku Y, Ishii K, Ishiki A, Nagai Y, Teramukai S, Ihara M, Fukushima M. 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 Dec 29;9:25424823251407541. doi: 10.1177/25424823251407541. eCollection 2025 Jan-Dec.

  PMID: 41477670 DERIVED

• Shimokawa H, Akishita M, Ihara M, Teramukai S, Ishiki A, Nagai Y, Fukushima M. Pivotal trial of low-intensity pulsed ultrasound therapy for early Alzheimer's disease: Rationale and design. J Alzheimers Dis Rep. 2025 Jan 13;9:25424823241312108. doi: 10.1177/25424823241312108. eCollection 2025 Jan-Dec.

  PMID: 40034530 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Hiroaki Shimokawa

  Sound Wave Innovation CO., LTD.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2023
• First Posted: August 9, 2023
• Study Start: October 31, 2023
• Primary Completion: January 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

JP (19)