Mild Neurocognitive Disorder Clinical Trial
Official title:
Efficacy of a 24-week Long Term Transcranial Pulse Stimulation (TPS) on Cognition and Brain Structure in Older Adults With Mild Neurocognitive Disorder (NCD)
NCT number | NCT05602467 |
Other study ID # | UW22-642 |
Secondary ID | |
Status | Recruiting |
Phase | N/A |
First received | |
Last updated | |
Start date | November 25, 2022 |
Est. completion date | August 2024 |
Background: Dementia, now known as major neurocognitive disorder (NCD), is a great health burden in Hong Kong and worldwide. In principle, to achieve its optimal benefits, intervention for dementia should begin at the earliest preclinical stage, which is defined as mild cognitive impairment (MCI). However, no evidence has been found to support a pharmacological approach to the prevention or postponement of cognitive decline during the stage of mild NCD. Non-invasive brain stimulation (NIBS) is increasingly recognized as a potential alternative to tackle this problem. The typical examples of NIBS are transcranial direct current stimulation (DCS) and transcranial magnetic stimulation (MS). Besides these, there is a new NIBS named transcranial pulse stimulation (TPS), which recently obtained CE marking in 2018 for the treatment of the central nervous system (CNS) in patients with mild to moderate Alzheimer's disease (AD). TPS is using repetitive single ultrashort pulses in the ultrasound frequency range to stimulate the brain. With a neuro-navigation device, TPS can achieve this in a highly focal and precisely targeted manner. TPS differs from DCS and TMS using direct or induced electric current. Instead, TPS provides good spatial precision and resolution to noninvasively modulate subcortical areas, despite the problem of skull attenuation. Using lower ultrasound frequencies TPS can successfully improve skull penetration in humans. TPS has shown its neuroprotective effects through inducing long term neuroplastic changes, supported by neuropsychological tests and neuroimaging investigations both in animal and human studies. Mild NCD is a golden period for intervention to avoid further progression to dementia. Although TPS has great potential as a new treatment option due to its neuroprotective effects, there is no TPS study done on mild CD subjects according to our knowledge. To determine the effectiveness of TPS in mild NCD, an open-label pilot study was conducted by our team from Dec 2020 to Dec 2021. The preliminary result was presented in the 2021 Brain Stimulation Conference and published in abstract format. We recruited 16 older adults who had mild CD. They received 6 sessions of TPS over 2 weeks. Assessments were done at the 3 time points. No subjects dropped out during the study. Statistically significant improvement was found in the primary outcome, HK-MoCA, from 18.06 to 20.25. The improvement was maintained till 12 weeks after the TPS intervention. No adverse effect was observed. The result suggested that TPS is likely to have an immediate effect on global cognition in mild CD, and the improvements were sustainable. However, a 2-week treatment duration may not be long enough to induce a significant change in neurodegenerative disease in long term. Up to date, there is no long-term NIBS treatment done on NCD. Therefore, we plan to conduct a pilot case-controlled trial to evaluate the efficacy of long-term TPS on cognition and brain structure in patients with mild ND based on the results of our pilot study. Objective: This study is to determine the efficacy of a 24-week program (32 sessions) of TPS in older adults with mild NCD. We hypothesized that TPS group is significantly more effective than control group in maintain or improve the global cognitive function measured by Hong Kong Chinese version of Montreal Cognitive Assessment (HK-MoCA) in patients with mild NCD. Design: This case-controlled trial will assess the efficacy of a 24-week TPS program on cognition and brain structure in subjects with mild NCD. All eligible participants will receive an intervention trial of TPS. They would receive 2 sets of stimulation programs, each set lasting 12-weeks. Participants would receive 3 sessions/week in the first 2 weeks and then 1 session/week in the subsequent 10 weeks. A total of 32 sessions (2 sets of 16 sessions) ofTPS will be delivered, with each session lasting 30 minutes. Data Analysis: The primary and secondary outcomes will be assessed at baseline, immediately after the 1st set of stimulation program (12th week), 2nd set of stimulation program (24th week), and 12 weeks after the intervention (36th week). The primary outcome will be the change of the Hong Kong Chinese version of the Montreal Cognitive Assessment (HK-MoCA). The secondary outcome includes specific cognitive domains, daily functioning, mood, and apathy. The intention-to-treat analysis would be carried out. Pre and post-intervention brain MRI scans will be used during the intervention to evaluate the changes in brain structure. A checklist of potential adverse effects associated with TPS administration will be generated from the available literature. Blood pressure and heart rate will be recorded at the beginning and at the end of the TPS intervention course.
Status | Recruiting |
Enrollment | 22 |
Est. completion date | August 2024 |
Est. primary completion date | August 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 60 Years and older |
Eligibility | Inclusion Criteria: 1. 60 years of age or above 2. Chinese ethnicity 3. Fulfil the criteria of mild neurocognitive disorder (NCD), defined by the DSM-5 4. Stable dosage/frequency of anti-dementia therapy or other treatments for mild NCD in recent 8 weeks 5. Valid informed written consent Exclusion Criteria: 1. HK-MoCA score below the second percentile according to the subject's age and education level (to exclude subjects with existing major NCD/dementia) 2. Alcohol or substance dependence 3. Concomitant unstable major medical conditions or major neurological conditions such as brain tumour, recent stroke 4. Haemophilia or other blood clotting disorders or thrombosis 5. Significant communicative impairments 6. Participants with any metal implant in brain or treated area of the head |
Country | Name | City | State |
---|---|---|---|
Hong Kong | The Hong Kong Jockey Club Building for Interdisciplinary Research | Hong Kong |
Lead Sponsor | Collaborator |
---|---|
The University of Hong Kong | Storz Medical AG |
Hong Kong,
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* Note: There are 21 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Change in Global Cognition | Global cognitive function measured by the Hong Kong Chinese version of the Montreal Cognitive Assessment (HK-MoCA) ranges from 0 to 30, with higher scores indicating better cognition. | Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up | |
Secondary | Change in Memory | Measured by Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) - Chinese version | Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up | |
Secondary | Change in Executive Function | Measured by Stroop test. | Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up | |
Secondary | Change in Attention/Working Memory | Measured by Trail Making Test Parts A and B | Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up | |
Secondary | Change in Brain Structure | Structural MRI will be performed using a 3T scanner at HKU. Pre and post intervention brain MRI scan will be used during intervention and evaluate the changes in brain structure. The participants' brain images will be loaded into the TPS machine before the session start. Those participants with abnormal brain scan result such as brain tumour and recent stroke will be excluded. Images processing and analysis will be performed using software packages including FSL and SPM8 to assess the voxel-based morphometry (VBM) in hippocampus and other relevant regions. | Baseline, 12-week Follow-up | |
Secondary | Change in Daily Functioning | Measured by Hong Kong Chinese version of the Lawton Instrumental Activities of Daily Living Scale. | Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up | |
Secondary | Change in Mood | Measured by the Depression Rating Scale (HAMD-17) | Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up |
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