臨床研究等提出・公開システム

Clinical study to evaluate the efficacy and safety of Ultra-Ma in patients diagnosed as having Lewy bodies dementia

Clinical study to evaluate the efficacy and safety of Ultra-Ma in patients diagnosed as having Lewy bodies dementia

12

4 males (33.3%), 8 females (66.7%), 2 hospitalized/outpatient (16.7%), 10 outpatient (83.3%), 10 self-powered walking in daily life (83.3%), 1 chair living (8.3%), 7 with medical history (58.3%), 5 without (41.7%), and 12 with complications (100.0%). None in 0 patients (0.0%), none in 12 patients (100.0%), and none in 0 patients (0.0%) with concomitant therapy related to dementia, and none in 12 patients (100.0%). Age at informed consent (mean +- SD (median), the same below) was 81.4 +- 3.60 (82.0) years, height was 153.8 +- 11.22 (152.0) cm, weight was 51.31 +- 10.088 (50.6) kg, and Hachinski score was 1.2 +- 0.98 (1.0) points.

Twelve patients who gave informed consent were enrolled, and this clinical research instrument was used. The safety analysis set consisted of 12 patients in both sham-stimulated and real-stimulated phases, 12 patients each in the FAS analysis set, and 11 patients each in the PPS analysis set. Twenty patients were initially planned, but the interim analysis was conducted at the stage of implementation in 12 patients due to the restriction of entries associated with the epidemic of COVID-19. Based on the results, this study was concluded in 12 patients, and the clinical study report was submitted.

No occurrence

Primary endpoint 1) NPI-Q severity (Total of 10 items) 1.Improvement in NPI-Q severity was markedly improved in 1 patient (8.3%), improved in 3 patients (25.0%), mildly improved in 3 patients (8.3%), mildly worsened in 2 patients (16.7%), markedly worsened in 0 patients (0.0%), markedly improved in 4 patients (33.3%), improved in 1 patient (8.3%), slightly improved in 2 patients (16.7%), unchanged in 3 patients (25.0%), mildly worsened in 1 patient (8.3%), and worsened in 1 patient (8.3%). Markedly worsened in 0 patients (0.0%), showing a significant improvement over the sham stimulation phase (Wilcoxon signed rank test p=0.03125). 2.The percentage change in NPI-Q severity was 9.95+-61.857% in the sham stimulation phase (after 4 weeks), 32.03+-50.691% in the real stimulation phase (after 8 weeks), and 35.04+-56.850% in the real stimulation phase (after 12 weeks). Compared with the sham stimulation phase (after 4 weeks), the real stimulation phase (after 8 weeks) (Wilcoxon signed rank test p=0.0420) and the real stimulation phase (after 12 weeks) (Wilcoxon signed rank test p=0.0039) showed significant improvement. 2) NPI-Q burden (Total of 10 items) 1.In the sham-stimulation period, improvement in NPI-Q burden was markedly improved in 3 patients (25.0%), improved in 0 patients (0.0%), slightly improved in 3 patients (25.0%), unchanged in 5 patients (41.7%), mildly worsened in 0 patients (0.0%), worsened in 0 patients (0.0%), markedly worsened in 1 patient (8.3%), markedly improved in 3 patients (25.0%), improved in 1 patient (8.3%), slightly improved in 3 patients (25.0%), unchanged in 3 patients (25.0%), mildly worsened in 2 patients (16.7%), and worsened in 0 patients (0.0%), Markedly worse 0 patients (0.0%) showed no significant improvement in the real stimulation phase than in the sham stimulation phase (Wilcoxon signed rank test p=0.4375). 2.The percentage change in NPI-Q burden was 6.10+-136.546% during the sham stimulation phase (after 4 weeks), 48.64+-81.794% during the real stimulation phase (after 8 weeks), and 51.09+-54.591% during the real stimulation phase (after 12 weeks). Compared with the sham stimulation phase (after 4 weeks), the real stimulation phase (after 8 weeks) (Wilcoxon signed rank test p=0.0645) and the real stimulation phase (after 12 weeks) (Wilcoxon signed rank test p=0.1484) showed no significant improvement. 3) MMSE Percent change in MMSE was -3.5+-17.50% during the sham stimulation phase (after 4 weeks), -12.1+-14.57% during the real stimulation phase (after 8 weeks), and -0.7+-16.09% during the real stimulation phase (after 12 weeks), showing a significant improvement during the real stimulation phase (after 8 weeks) (Wilcoxon signed rank test p=0.0186) compared to the sham stimulation phase (after 4 weeks). Secondary endpoints 1) UPDRSIII motor function test The change rate of UPDRSIII motor function test was-4.6 +- 21.29% in sham stimulation phase (after 4 weeks), 12.3 +- 30.67% in real stimulation phase (after 8 weeks), and 26.0 +- 36.79% in real stimulation phase (after 12 weeks), and it showed significant improvement in real stimulation phase (after 8 weeks) (Wilcoxon signed rank test p=0.0156) and real stimulation phase (after 12 weeks) (Wilcoxon signed rank test p=0.0039) compared with sham stimulation phase (after 4 weeks). 2) MoCA-J The percentage change in MoCA-J was-9.2 +- 26.20% during the sham-stimulation phase (after 4 weeks), -6.7 +- 19.75% during the real-stimulation phase (after 8 weeks), and 2.2 +- 22.58% during the real-stimulation phase (after 12 weeks), and showed no significant improvement during the real-stimulation phase (after 8 weeks) (Wilcoxon signed rank test p=0.6558) and the real-stimulation phase (after 12 weeks) (Wilcoxon signed rank test p=0.3077) compared with the sham-stimulation phase (after 4 weeks). 3) Zarit-8 The change rate transition of Zarit-8 was-22.7 +- 120.27% in sham stimulation phase (after 4 weeks), 17.9 +- 85.06% in real stimulation phase (after 8 weeks), and 51.2 +- 27.05% in real stimulation phase (after 12 weeks), showing significant improvement in real stimulation phase (after 12 weeks) (Wilcoxon signed rank test p=0.0233) compared to sham stimulation phase (after 4 weeks). 4) CFI The percentage change in CFI was 47.0+-48.63% in the sham-stimulated phase (after 4 weeks), 35.6+-89.43% in the real-stimulated phase (after 8 weeks), and 62.5+-38.23% in the real-stimulated phase (after 12 weeks). Compared with the sham-stimulated phase (after 4 weeks), the real-stimulated phase (after 8 weeks) (Wilcoxon signed rank test p=0.7813) and the real-stimulated phase (after 12 weeks) (Wilcoxon signed rank test p=0.3125) showed no significant improvement. 5) BI The percentage change in BI was-2.9 +- 16.17% during the sham-stimulation phase (after 4 weeks), -7.2 +- 17.95% during the real-stimulation phase (after 8 weeks), and-5.4 +- 16.14% during the real-stimulation phase (after 12 weeks), and showed no significant improvement during the real-stimulation phase (after 8 weeks) (Wilcoxon signed rank test p=0.4631) and the real-stimulation phase (after 12 weeks) (Wilcoxon signed rank test p=1.000) compared with the sham-stimulation phase (after 4 weeks). Safety evaluation No adverse events or malfunctions were observed in the sham-stimulated and real-stimulated phases.

From improvement and change in NPI-Q severity, BPSD was confirmed a certain improvement. Zarit-8 improvements may have a certain effect on reducing the burden on caregivers. Improvement in MMSE indicated a certain improvement in cognitive function. The percentage change in UPDRSIII was significantly improved indicated the parkinsonian symptoms associated with dementia with Lewy bodies. The limited analysis suggested the usefulness of Ultra-Ma. A validation study should be conducted based on this study.

June. 10, 2021

No

https://jrct.niph.go.jp/latest-detail/jRCTs032190012

Manabe Yuta

Kanagawa Dental University Hospital

1-23, Ogawa-cho, Yokosuka-shi, Kanagawa

manabe.epikuros@gmail.com

Murakami Takeshi

Kanagawa Dental University

82, Inaoka-cho, Yokosuka-shi, Kanagawa

+81-46-822-9690

murakami@kdu.ac.jp

Complete

April. 01, 2019

Interventional

single arm study

single blind

no treatment control/standard of care control

single assignment

other

-Hachinski ischemic score <= 4 points
-CDR-J >= 0.5 points, with mild cognitive impairment and dementia
-MMSE score of 11 to 27 points
-1 point >= some of the items of NPI-Q
-Diagnosed as "Probable DLB" as per the clinical diagnostic criteria of Lewy body dementia (CDLB Guideline 2017)
-Home care patient who satisfy the following criteria. Has a family or caregiver who can always observe the condition. Receiving more than two thirds of nursing care by one parson.
-Ability to keep symptom diary by himself/herself or by a caregiver
-Either or both of the following treatment has been effective for four weeks or more before the study begins
1) Cholinesterase inhibitors
2) L-dopa preparations

-Active dementia other than Lewy body dementia
-Hachinski ischemic score >=5 points and suspected of vascular dementia complications through imaging findings of MRI or CT scan performed within a year before the consent (Focal brain lesions or multiple infarctions, known as the cause of dementia, are observed)
-Has any severe neuropsychiatric disorder complications such as cerebrovascular disorder, brain tumor, schizophrenia, epilepsy, normal-pressure hydrocephaly, mental retardation, head trauma with disturbed consciousness, history of brain surgery with residual defect, and so on.
-Has severe parkinsonian symptoms (Hoehn & Yahr severity category >= IV)
-Unable to perform MMSE and/or NPI-Q tests and so on (has visual and/or hearing impairment, and/or aphasia.
-Bedridden patient or inhabitants of an institution(health institution for elderly, rehabilitation facility for elderly, and so on )
-Use of any implantable medical electrical equipment, such as pacemaker and/or implantable defibrillation equipment, which are susceptible to the impact of electromagnetic interference
-Any metal components placed inside the skull (ex. indwelling coil)
-Use of any In-the-ear (ITE) hearing aid,cochlear implant,or middle ear implant.
-Has participated in other clinical research or clinical study for Lewy body dementia within a year before the time of consent

Both

Dementia with Lewy Bodies

Cranial ultrasound by [Ultra-Ma]

-NPI-Q
-MMSE

-UPDRSIII
-MoCA-J
-Adverse events
-Device failure

+81-3-3588-1111

April. 04, 2019

none