Sound Wave Innovation CO., LTD. (Head Office: Chuo-ku, Tokyo; President: Hajime Kato; SWI), which aims for the social implementation of the LIPUS-Brain Transcranial Low-Intensity Pulsed Ultrasound (LIPUS) device, a world-leading medical treatment device in the treatment of dementia, has submitted a notification to the PMDA for the pivotal clinical trial to evaluate the efficacy and safety of the LIPUS-Brain Transcranial Low-Intensity Pulsed Ultrasound (LIPUS) device for early-stage Alzheimer’s disease patients.Submitted a notification of clinical trial plan to the Pharmaceuticals and Medical Devices Agency (PMDA) on 26 May 2023. This notification has been accepted by the PMDA.

※The details of the notification are available on the Clinical Research Submission and Publication System.
Clinical research plan number: jRCT2032230125
Clinical research submission and publication system (https://jrct.niph.go.jp/search)

【Background.】
 Currently, there are approximately 6 million people in Japan and 60 million people worldwide with dementia, and this number is predicted to reach 150 million by 2050 (*1 *2). In addition, Alzheimer’s disease (AD) accounts for approximately 70% of all dementia cases, and cerebrovascular dementia (VaD) for 20%, with these two types accounting for the majority of dementia cases. However, there are no safe and effective treatments for dementia, and the establishment of treatment methods is a major social issue worldwide. LIPUS is an innovative treatment technology that activates the self-healing powers inherent in humans by irradiating ultrasound from outside the body, and has been strongly suggested to be safe and effective in treating dementia through exploratory trials to date.

※1　Research on future estimates of the elderly population with dementia in Japan (Health and Labour Science Special Research Project funded by the Health and Labour Science Research Grant, 2014).

※2　Estimation of the number of people with dementia worldwide: The Lancet Public Health ‘Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050’.
https://doi.org/10.1016/S2468-2667(21)00249-8

【About the trial】
 LIPUS therapy is an innovative treatment technology that uses minimally invasive and safe special ultrasound to activate the self-healing powers of the human body, enabling the treatment of various diseases that are difficult to treat with existing drugs and medical devices.
 Ultrasound has been used in medical practice around the world for more than 40 years as echocardiography and abdominal echography. Its safety is well established and it is widely used for all types of people, including pregnant women and children.
 In the ultrasound treatment performed in this study, the ultrasound irradiation conditions for diagnostic ultrasound are applied to the treatment device by changing the settings to those for treatment.

 A total of 220 patients (110 in the actual treatment group and 110 in the placebo treatment group) will participate in the pivotal trial at 15 facilities nationwide and will be randomly assigned to either the actual treatment group (who will actually receive ultrasound treatment) or the placebo treatment group (who will not receive ultrasound treatment as the device is set not to emit ultrasound waves). (Double-blind randomized, placebo-controlled trial)
 In recent years, ultrasound therapy has attracted attention from the viewpoint that the cause of dementia is cerebrovascular disorders, and its efficacy and safety have been confirmed in animal experiments. The Department of Cardiovascular Medicine at Tohoku University has also confirmed that whole-brain ultrasound (LIPUS) suppresses the progression of dementia in animal experiments on cerebrovascular dementia and Alzheimer’s disease (*3).
 Furthermore, no apparent complications, including death, were observed in mice treated with this ultrasound therapy. Next, an exploratory trial conducted with 27 patients with early-stage Alzheimer’s disease also confirmed the safety strongly suggested its efficacy of the treatment (*4). If the efficacy and safety of this ultrasound therapy is finally recognized in Alzheimer’s disease patients, it is expected to become a new dementia treatment method completely different from conventional drug therapies.

※3　Eguchi K, Shmokawa H, et al. Whole-brain low-intensity pulsed ultrasound therapy markedly improves cognitive dysfunctions in mouse models of dementia-Crucial roles of endothelial nitric oxide synthase- Brain Stim. 11:959-973,2018.
https://www.cardio.med.tohoku.ac.jp/2020/jp/res/pr/files/press20180619.pdf

※4　The results of Professor Shimokawa’s exploratory trial of ultrasound therapy for early Alzheimer’s disease were published online in the Tohoku Journal of Experimental Medicine and a press release from Tohoku University
https://sw-innovation.com/news/paper/1132/

【Comment from Hiroaki Shimokawa, founder and chairman of the board of directors of SWI.】
 Alzheimer’s disease and atherosclerotic diseases have many similarities in terms of risk factors and prevention methods. I have been conducting research based on the hypothesis that Alzheimer’s disease also starts as a vascular disease and that the progression of chronic inflammation associated with microcirculatory disturbance may be its cause. The efficacy and safety of the ameliorative effects on microcirculatory disturbance and chronic inflammation that I discovered with ultrasound (LIPUS) treatment were confirmed in a mouse model of Alzheimer’s disease, and safety was also confirmed in a pilot trial conducted in a small number of patients, strongly suggesting efficacy. As a result, the LIPUS treatment device was designated as the first ‘pioneering medical device’ by the MHLW as of 30 September 2022. By conducting pivotal trials (randomized, placebo-controlled, double-blind comparative trials) over the next three years, we hope to finally confirm the efficacy and safety of the LIPUS treatment and bring this novel treatment to patients and families with Alzheimer’s disease as soon as possible.

【Outline of Sound Wave Innovation CO., LTD.】
 Company Name：Sound Wave Innovation CO., LTD.
Headquarter：1-9-10, Nihonbashi-horidomecho, Chuo-ku, Tokyo, 103-0012, Japan
President & CEO：Hajimu　Kato
URL：https://sw-innovation.com/

【Biography of Hiroaki Shimokawa, Founder, Chairman & CMO】
Graduated from Kyushu University Faculty of Medicine (M.D.). He was a member of the Department of Cardiovascular Medicine at Kyushu University for 14 years, and became a professor of Tohoku University Graduate School of Medicine in 2005 and an emeritus professor and visiting professor of the Tohoku University in 2020 (current position). Deputy Dean of the International University of Health and Welfare, International University of Health and Welfare (to date); Visiting Professor of Kurume University (to date); founded the Company in April 2020 and became the Director; Chairman of the Board and CMO (Chief Medical Officer) of the Company from 2022.