Transcranial Pulse Stimulation. a Potential Treatment for Early Dementia

Transcranial Pulse Stimulation: a Potential New Treatment for Chronic Disorders of Consciousness/Cognition Due to Vegetative/Minimally Conscious States and Early Dementia

Alzheimer's Disease (AD) is characterized by the absence of treatments to slow, stop, or reverse its course, with patients finally losing cognitive functions, skills and independence. It is a chronic degenerative disease with high social and medical burden worldwide: AD ranked third among neurological disorders in terms of disability-adjusted life years (DALY) rates.

The primary aim of the research protocol is to improve care for patients with AD, by implementing, with an innovative method, the currently available repertoire of neuromodulation techniques. For this aim, we will investigate whether Transcranial Pulse Stimulation (TPS) may induce cognitive improvement in patients with an early stage of dementia.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Device: Transcranial Pulse Stimulation

Detailed Description

Aims of the project: The primary aim of our research protocol is to improve care for patients with AD by investigating whether Transcranial Pulse Stimulation (TPS) may induce cognitive improvement in patients with an early stage of dementia. Additional aims will include the investigation of the neurophysiological profile of patients and the search for a correlation between neuropsychological and neurophysiological data with the serum levels of brain-derived neurotrophic factor (BDNF) and of vascular endothelial growth factor (VEGF).

Materials and Methods: Following a rigorous selection, included patients will be treated through a real/sham structured TPS protocol and followed-up with respect to cognitive improvement, by comparing baseline and follow-up clinical scores. A Double Blind Sham-Controlled Study will be performed: patients will be assigned randomly to receive TPS or sham TPS for 4 weeks in a parallel groups, double-blind study. Patients will receive ether TPS or sham treatment once a day for five days a week for the whole period and will be assessed according to the following schedule: baseline (t0); at two weeks following the start of TPS (t1); at 1 month following the start of TPS (t2); at 2 months following the start of TPS (t3); at 6 months following the start of TPS (t4). Electroencephalography (EEG) and Somatory Evoked Potentials (SEP) will be contextually recorded in all patients, to compare neurophysiological data of patients treated with real TPS and sham stimulation. Moreover, a serum sample will be collected from patients at baseline, at the end of the stimulation period and at the 6-month follow-up, to compare preprocedural and postprocedural levels of serum BDNF and VEGF.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Francesca Pistoia, MD, PhD; Phone Number: +39862368657; Email: francesca.pistoia@univaq.it

Study Locations

• Italy
  • L'Aquila, Italy, 67100
    • Recruiting
    • San Salvatore Hospital
    • Contact: Francesca Pistoia, MD, PhD; Phone Number: +39862368657; Email: francesca.pistoia@univaq.it
    • Contact: Francesca Pistoia, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age>18 years
• diagnosis of early dementia according to current international guidelines
• disease duration of at least 12 months
• consent to participate in the study.

Exclusion Criteria:

• medical instability interfering with standard neurological assessment
• any contraindication to preliminary MRI for MR-based real-time neuronavigation
• comorbidities which may interfere with cognitive status
• any contraindication to Transcranial Pulse Stimulation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transcranial pulse stimulation; Patients belonging to this group will receive real transcranial pulse stimulation over a 4-weeks period, once a day for five days a week.	Device: Transcranial Pulse Stimulation; Patients will receive TPS once a day for five days a week, each session will be separated from the previous one by 24h. Each stimulation and assessment session will be performed at the same hour of the day, in the morning preferably, to maximize the probability of observing responses to stimuli. Patients will be managed in a quiete room with stable light and temperature.
Sham Comparator: Sham stimulation Group; Patients belonging to this group will receive sham transcranial pulse stimualtion over a 4-weeks period, once a day for five days a week.	Device: Transcranial Pulse Stimulation; Patients will receive TPS once a day for five days a week, each session will be separated from the previous one by 24h. Each stimulation and assessment session will be performed at the same hour of the day, in the morning preferably, to maximize the probability of observing responses to stimuli. Patients will be managed in a quiete room with stable light and temperature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive improvement	Cognitive improvement as evaluated by means of the ADAS-Cog, scores range from 0, that means the absence of cognitive dysfunctions, to a maximum of 70, that indicates a serious deficit in all tests.	Two weeks following the start of TPS (t1); at 1 month following the start of TPS (t2); at 2 months following the start of TPS (t3); 6 months following the start of TPS (t4).

Collaborators and Investigators

• Sponsor: Francesca Pistoia

Publications and helpful links

General Publications

• Beisteiner R, Matt E, Fan C, Baldysiak H, Schonfeld M, Philippi Novak T, Amini A, Aslan T, Reinecke R, Lehrner J, Weber A, Reime U, Goldenstedt C, Marlinghaus E, Hallett M, Lohse-Busch H. Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. Adv Sci (Weinh). 2019 Dec 23;7(3):1902583. doi: 10.1002/advs.201902583. eCollection 2020 Feb.
• Matt E, Kaindl L, Tenk S, Egger A, Kolarova T, Karahasanovic N, Amini A, Arslan A, Saricicek K, Weber A, Beisteiner R. First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. J Transl Med. 2022 Jan 15;20(1):26. doi: 10.1186/s12967-021-03222-5.

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Dementia; Transcranial Pulse Stimulation; Alzheimer's disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease; Dementia
• Other Study ID Numbers: PNRR-MCNT2-2023-12377235 (Other Grant/Funding Number: Ministry of Health (Italy))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No