Clinical trial NCT05983575: A Pivotal Study of LIPUS-Brain in Patients With Early Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Alzheimer Disease, Early Onset
Lead sponsor: Sound Wave Innovation CO., LTD.
Sponsor class: INDUSTRY
First posted: 2023-08-09
Enrollment: 220
Sex: ALL
Minimum age (years): 50
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Changes in ADAS-J-cog-14 scores from baseline to Week 72
timeFrame: Performed at Week 72
Secondary outcomes:
measure: Changes in ADAS-J-cog-14 scores from baseline to Week 24 and 48
timeFrame: Performed at Week 24 and 48
measure: Changes in CDR-SB from baseline to Week 48 and 72
timeFrame: Performed at Week 48 and 72
measure: Changes in NPIQ-J scores from baseline to Week 24, 48 and 72
timeFrame: Performed at Week 24, 48 and 72
measure: Changes in J-ZBI scores from baseline to Week 24, 48 and 72
timeFrame: Performed at Week 24, 48 and 72
measure: Changes in WMS-R scores from baseline to Week 24, 48 and 72
timeFrame: Performed at Week 24, 48 and 72
measure: Changes in MMSE-J scores from baseline to Week 24, 48 and 72
timeFrame: Performed at Week 24, 48 and 72
measure: Changes in FAQ scores from baseline to Week 24, 48 and 72
timeFrame: Performed at Week 24, 48 and 72
measure: Changes in EQ-5D-5L scores from baseline to Week 24, 48 and 72
timeFrame: Performed at Week 24, 48 and 72
measure: Changes in ABC Dementia scale scores from baseline to Week 24, 48 and 72
timeFrame: Performed at Week 24, 48 and 72
measure: Changes in each 14 item of ADAS-J-cog-14 score from baseline to Week 24, 48 and 72
timeFrame: Performed at Week 24, 48 and 72
measure: Prevalence of responders at Week 24, 48, and 72 defined as those with no deterioration or even improvement in ADAS-J-cog-14 scores
timeFrame: Performed at Week 24, 48 and 72
measure: Transition rate from MCI due to AD to AD at Week 72
timeFrame: Performed at Week 72
measure: Termination due to aggravation of dementia symptoms
timeFrame: Performed up to 96 weeks
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Ōbu
country: Japan
facility: National Center for Geriatrics and Gerontology
state: Aichi
city: Narita
country: Japan
facility: IUHW Narita Hospital
state: Chiba
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Toride
country: Japan
facility: Memory Clinic Toride
state: Ibaragi
city: Kanazawa
country: Japan
facility: Kanazawa University Hospital
state: Ishikawa
city: Sendai
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Kurashiki
country: Japan
facility: KATAYAMA medical Clinic
state: Okayama
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
state: Osaka
city: Suita
country: Japan
facility: National Cerebral and Cardiovascular Center
state: Osaka
city: Nasushiobara
country: Japan
facility: International University of Health and welfare Hospital
state: Tochigi
city: Bunkyō-Ku
country: Japan
facility: Juntendo University School of Medicine Juntendo Hospital
state: Tokyo
city: Bunkyō-Ku
country: Japan
facility: Memory Clinic Ochanomizu
state: Tokyo
city: Bunkyō-Ku
country: Japan
facility: The University of Tokyo Hospital
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Tokyo Metropolitan Geriatrics Hospital
state: Tokyo
city: Yonago
country: Japan
facility: Tottori University Hospital
state: Tottori
city: Fukuoka
country: Japan
facility: Fukuoka Sanno Hospital
city: Hiroshima
country: Japan
facility: Imon Yukari Neurology Clinic
city: Niigata
country: Japan
facility: Niigata University Medical and Dental Hospital
Study officials:
affiliation: Sound Wave Innovation CO., LTD.
name: Hiroaki Shimokawa
role: STUDY_DIRECTOR
References: