Alzheimer Disease, Early OnsetPhase 3NCT05983575
A Pivotal Study of LIPUS-Brain in Patients With Early Alzheimer's Disease
A Phase 3 study testing LIPUS-Brain in people with Alzheimer Disease, Early Onset, run by Sound Wave Innovation CO., LTD. at 19 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 89 years
- Conditions the study is for
- Alzheimer Disease, Early Onset
- What is being tested?
- LIPUS-Brain
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 220 participants
- Where
- 19 sitesJapan
- Study dates
- 31 Oct 2023to 31 Jul 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
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- 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.
- Patients participating in other clinical studies (excluding non-interventional observational studies) or clinical trials.
- Patients who are otherwise judged to be ineligible by the investigator.
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
Japan19 sites
Juntendo University School of Medicine Juntendo Hospital
Bunkyō-Ku, Tokyo, 113-0033
Memory Clinic Ochanomizu
Bunkyō-Ku, Tokyo, 113-0034
The University of Tokyo Hospital
Bunkyō-Ku, Tokyo, 113-8655
Fukuoka Sanno Hospital
Fukuoka, Fukuoka, 814-0001
Kansai Medical University Hospital
Hirakata, Osaka, 573-1191
Imon Yukari Neurology Clinic
Hiroshima, Hiroshima, 732-0066
Kanazawa University Hospital
Kanazawa, Ishikawa-ken, 920-8641
KATAYAMA medical Clinic
Kurashiki, Okayama-ken, 710-0813
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560
IUHW Narita Hospital
Narita, Chiba, 286-8520
International University of Health and welfare Hospital
Nasushiobara, Tochigi, 329-2763
Niigata University Medical and Dental Hospital
Niigata, Niigata, 951-8122
National Center for Geriatrics and Gerontology
Ōbu, Aichi-ken, 474-8511
Sapporo Medical University Hospital
Sapporo, Hokkaido, 060-8543
Tohoku University Hospital
Sendai, Miyagi, 980-8574
National Cerebral and Cardiovascular Center
Suita, Osaka, 564-8565
Tokyo Metropolitan Geriatrics Hospital
tabashi City, Tokyo, 173-0015
Memory Clinic Toride
Toride, Ibaragi, 302-0004
Tottori University Hospital
Yonago, Tottori, 683-8504
About this study
Official title: A Study to Evaluate the Efficacy and Safety of LIPUS-Brain Transcranial Low-intensity Pulsed-wave Ultrasound Device in Patients With Early Alzheimer's Disease
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
- Being tested
- LIPUS-Brain, Placebo
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LIPUS-BrainDevice
Transcranial low-power pulsed-wave ultrasound device
PlaceboDevice
Placebo
| Study group | Role | What they receive |
|---|---|---|
| LIPUS-Brain | Experimental | Not described Receives: Device: LIPUS-Brain |
| Placebo | Placebo comparator | Not described Receives: Device: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in ADAS-J-cog-14 scores from baseline to Week 72
Measured: Performed at Week 72
Secondary outcomes (13)
Changes in ADAS-J-cog-14 scores from baseline to Week 24 and 48
Measured: Performed at Week 24 and 48
Changes in CDR-SB from baseline to Week 48 and 72
Measured: Performed at Week 48 and 72
Changes in NPIQ-J scores from baseline to Week 24, 48 and 72
Measured: Performed at Week 24, 48 and 72
Changes in J-ZBI scores from baseline to Week 24, 48 and 72
Measured: Performed at Week 24, 48 and 72
Changes in WMS-R scores from baseline to Week 24, 48 and 72
Measured: Performed at Week 24, 48 and 72
Changes in MMSE-J scores from baseline to Week 24, 48 and 72
Measured: Performed at Week 24, 48 and 72
Changes in FAQ scores from baseline to Week 24, 48 and 72
Measured: Performed at Week 24, 48 and 72
Changes in EQ-5D-5L scores from baseline to Week 24, 48 and 72
Measured: Performed at Week 24, 48 and 72
Changes in ABC Dementia scale scores from baseline to Week 24, 48 and 72
Measured: Performed at Week 24, 48 and 72
Changes in each 14 item of ADAS-J-cog-14 score from baseline to Week 24, 48 and 72
Measured: Performed at Week 24, 48 and 72
Prevalence of responders at Week 24, 48, and 72 defined as those with no deterioration or even improvement in ADAS-J-cog-14 scores
Measured: Performed at Week 24, 48 and 72
Transition rate from MCI due to AD to AD at Week 72
Measured: Performed at Week 72
Termination due to aggravation of dementia symptoms
If medication needs to be started or changed, dementia is considered worsening.
Measured: Performed up to 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2023
- Study start31 Oct 2023
- Primary completion31 Jan 2026 (estimated)
- Study completion31 Jul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Alzheimer Disease, Early OnsetStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sound Wave Innovation CO., LTD.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Hiroaki Shimokawa, Study director, Sound Wave Innovation CO., LTD.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05983575
- Sponsor's protocol ID
- LB1101
- Status last verified
- May 2025
- First submitted
- 18 Jul 2023
- Last updated
- 15 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41477670Shimokawa 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.
PubMed 40034530
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study to Evaluate the Efficacy and Safety of LIPUS-Brain Transcranial Low-intensity Pulsed-wave Ultrasound Device in Patients With Early Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT05983575
- Acronym / sponsor ID
- LB1101
- Conditions
- Alzheimer Disease, Early Onset
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Sound Wave Innovation CO., LTD.Industry (pharma, biotech, devices)
- Study start
- 31 Oct 2023 (actual)
- Primary completion
- 31 Jan 2026 (estimated)
- Study completion
- 31 Jul 2026 (estimated)
- First posted
- 9 Aug 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LIPUS-Brain | Experimental | Device: LIPUS-Brain |
| Placebo | Placebo comparator | Device: Placebo |
Who may qualify
- Ages
- 50 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LIPUS-BrainTranscranial low-power pulsed-wave ultrasound device | Device | LIPUS-Brain |
| PlaceboPlacebo | Device | Placebo |
Primary outcome
Changes in ADAS-J-cog-14 scores from baseline to Week 72
Time frame: Performed at Week 72
13 secondary outcomes
Changes in ADAS-J-cog-14 scores from baseline to Week 24 and 48
Time frame: Performed at Week 24 and 48
Changes in CDR-SB from baseline to Week 48 and 72
Time frame: Performed at Week 48 and 72
Changes in NPIQ-J scores from baseline to Week 24, 48 and 72
Time frame: Performed at Week 24, 48 and 72
Changes in J-ZBI scores from baseline to Week 24, 48 and 72
Time frame: Performed at Week 24, 48 and 72
Changes in WMS-R scores from baseline to Week 24, 48 and 72
Time frame: Performed at Week 24, 48 and 72
Changes in MMSE-J scores from baseline to Week 24, 48 and 72
Time frame: Performed at Week 24, 48 and 72
Changes in FAQ scores from baseline to Week 24, 48 and 72
Time frame: Performed at Week 24, 48 and 72
Changes in EQ-5D-5L scores from baseline to Week 24, 48 and 72
Time frame: Performed at Week 24, 48 and 72
Changes in ABC Dementia scale scores from baseline to Week 24, 48 and 72
Time frame: Performed at Week 24, 48 and 72
Changes in each 14 item of ADAS-J-cog-14 score from baseline to Week 24, 48 and 72
Time frame: Performed at Week 24, 48 and 72
Prevalence of responders at Week 24, 48, and 72 defined as those with no deterioration or even improvement in ADAS-J-cog-14 scores
Time frame: Performed at Week 24, 48 and 72
Transition rate from MCI due to AD to AD at Week 72
Time frame: Performed at Week 72
Termination due to aggravation of dementia symptoms
Time frame: Performed up to 96 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
- Derived from this study: PubMed 41477670Shimokawa 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.
- Derived from this study: PubMed 40034530Shimokawa 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hiroaki Shimokawa study director
Sound Wave Innovation CO., LTD.
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LIPUS-Brain in people with Alzheimer Disease, Early Onset, run by Sound Wave Innovation CO., LTD. at 19 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in ADAS-J-cog-14 scores from baseline to Week 72 (time frame: Performed at Week 72). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05983575, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.