Long Term Transcranial Pulse Stimulation (TPS) on Older Adults With Mild Neurocognitive Disorder (NCD)

NCT05602467 | Unknown DMC

• 1 other identifier: UW22-642
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Neurocognitive Disorder

Keywords

TPS; Transcranial Pulse Stimulation; Mild Neurocognitive Disorder; Open-Label; long term intervention

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change in Memory

  Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up

• Change in Executive Function

  Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up

• Change in Attention/Working Memory

  Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up

• Change in Brain Structure

  Baseline, 12-week Follow-up

• Change in Daily Functioning

  Baseline, at 12 weeks, at 24 weeks, 12-week Follow-up

Study Arms (2)

Treatment Group

ACTIVE COMPARATOR

A total of 32 sessions (2 sets of 16 sessions) of TPS will be delivered, each lasting 30 minutes. Each set includes 3 sessions per week in the first 2 weeks and then 1 session per week in the subsequent 10 weeks.

Device: Transcranial Pulse Stimulation (TPS)

Control Group

PLACEBO COMPARATOR

The control group will be recruited with the same recruitment criteria. They would receive treatment-as-usual (TAU) in the outpatient clinic without TPS intervention given.

Other: Treatment as usual (TAU)

Interventions

Transcranial Pulse Stimulation (TPS) DEVICE

A global brain stimulation approach, which homogenously distributes the total energy of 6000 TPS pulses per session over all accessible brain areas. Prefrontal, Temporal and Occipital brain areas were stimulated by ultrashort (3μs) ultrasound pulses with typical energy levels of 0.2-0.25 mJ/mm2 and pulse frequencies of 4-5 Hz (pulses per second).

Treatment Group

Treatment as usual (TAU) OTHER

Treatment-as-usual (TAU) in the Hong Kong outpatient clinic without TPS intervention was given. They would receive the standard care for mild NCD including counselling, lifestyle modification, cognitive training and antidementia medications occasionally depending on the case doctor's judgement.

Control Group

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or above
• Chinese ethnicity
• Fulfil the criteria of mild neurocognitive disorder (NCD), defined by the DSM-5
• Stable dosage/frequency of anti-dementia therapy or other treatments for mild NCD in recent 8 weeks
• Valid informed written consent

You may not qualify if:

• HK-MoCA score below the second percentile according to the subject's age and education level (to exclude subjects with existing major NCD/dementia)
• Alcohol or substance dependence
• Concomitant unstable major medical conditions or major neurological conditions such as brain tumour, recent stroke
• Haemophilia or other blood clotting disorders or thrombosis
• Significant communicative impairments
• Participants with any metal implant in brain or treated area of the head

Sponsors & Collaborators

• The University of Hong Kong: lead
• Storz Medical AG: collaborator

Study Sites (1)

The Hong Kong Jockey Club Building for Interdisciplinary Research

Hong Kong, Hong Kong

RECRUITING

Related Publications (21)

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Related Links

• Cheng PWC, Fong KHT. Efficacy and safety of transcranial pulse stimulation (TPS) in older adults with mild neurocognitive disorder-an open-label trial. Brain Stimulation: Basic, Translational, and Clinical Research in Neuromodulation. 2021;14(6):1636.

MeSH Terms

Conditions

Neurocognitive Disorders

Interventions

Transcranial Magnetic Stimulation; Therapeutics

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy

Study Officials

• Calvin PW Cheng, MBBS (HKU)

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Calvin PW Cheng, MBBS (HKU)

CONTACT

+852-22554486; chengpsy@hku.hk

Tommy KH Fong, MPsyMed

CONTACT

+852-64214186; U3550211@connect.hku.hk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: The active group would receive 2 stimulation programs, each set last 12-week. 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 (16 sessions per set) of TPS will be delivered, each lasting 30 minutes. The control group will be recruited with the same recruitment criteria. They would receive treatment-as-usual (TAU) in the outpatient clinic without TPS intervention given.

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: November 2, 2022
• Study Start: November 25, 2022
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: July 27, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1)