Alzheimer DiseaseTPSAlzNCT07883148
TPSAlz - Transcranial Pulse Stimulation in Alzheimer's Disease
A study testing Transcranial pulse stimulation (TPS) in people with Alzheimer Disease and Mild Cognitive Impairment, run by IRCCS San Raffaele Roma at 1 site in Italy.
Trial summary
The goal of this study is to evaluate the effects of transcranial pulse stimulation (TPS) in modulating cognitive functions as well as structural and functional connectivity in individuals with mild cognitive impairment and early Alzheimer's disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Alzheimer Disease, Mild Cognitive Impairment
- What is being tested?
- Transcranial pulse stimulation (TPS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 52 participants
- Where
- 1 siteItaly
- Study dates
- 30 May 2024to 30 Sep 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals aged ≥18 years; if women, in menopause since at least 2 years;
- fulfilling the diagnostic criteria for MCI due to AD;
- Mini-Mental State Examination (MMSE) score ≥24;
- Clinical Dementia Rating (CDR) ≤0.5;
- Stable presence of an informant family member;
- Release of written informed consent prior to the study participation;
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- Capacity of full compliance with the protocol requirements.
- Individuals aged ≥18 years; if women, in menopause since at least 2 years;
- Fulfilling the diagnostic criteria for AD;
- Mini-Mental State Examination (MMSE) score ≥18;
- Clinical Dementia Rating (CDR) =1;
- At least 3 months of stable antidementia therapy (if any);
- Stable presence of an informant family member;
- Release of written informed consent prior to the study participation;
- Capacity of full compliance with the protocol requirements.
Who cannot join
- Exclusion criteria for both MCI due to AD and AD will be the following:
- Individuals with comorbidities which may interfere with cognitive status (e.g., previous stroke, normal pressure, hydrocephalus, alcohol abuse, brain tumor or brain metastasis);
- Previous medical history positive for psychiatric diseases (except for a recent onset of depression or other behavioral disturbances);
- Treatments which may interfere with cognitive status;
- Blood clotting disorders, epilepsy, and corticosteroid treatment in the last 6 weeks;
- Any contraindication to TPS;
- Non-compliance with the protocol requirements.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Transcranial Pulse Stimulation on Functional and Structural Brain Connectivity in Mild Cognitive Impairment and in the Early Stages of Alzheimer's Disease
The goal of this study is to evaluate the effects of transcranial pulse stimulation (TPS) in modulating cognitive functions as well as structural and functional connectivity in individuals with mild cognitive impairment and early Alzheimer's disease. The main outcome measure is to confirm whether TPS may be considered as an effective treatment to improve memory in a large cohort of participants and investigating its long-term effects. Then, secondary measurements are to evaluate if TPS may induce neuronal connectivity changes and may confirm previous results exploring whether this innovative technique may induce, in a long and short-term period, possible effects on cortical atrophy and structural connectivity. An additional outcomes is to evaluate if TPS may have a positive impact on global cognitive functioning and behavioral profile.
Read the detailed description
The incidence of dementia is increasing worldwide, and great research efforts have been pointing towards novel therapeutic strategies to slow down or treat the occurrence of dementia.
Among non-invasive brain stimulation techniques, transcranial pulse stimulation (TPS) has recently demonstrated its potential in modulating brain functions and improving cognitive performances in Alzheimer's disease (AD) patients. Little is known on its effect on brain network organization/plasticity, particularly in prodromal stages of AD, such as Mild Cognitive Impairment (MCI). The proposal aims to evaluate whether TPS treatment may show positive effects on cognition, neuronal plasticity, and anatomical patterns in MCI due to AD and AD.
In the present placebo-controlled study, at least 26 individuals with MCI due to AD and 26 with AD will be recruited. These two groups will be matched by age, gender and years of education.
The data collection will be performed at baseline, at 1-month follow-up and at 8-month follow-up. At the baseline, all subjects will perform a complete neuropsychological assessment to evaluate cognitive functions, a high-density electroencephalogram (EEG) recording (128 channel) for the evaluation of the brain connectivity through graph theory indices, and a volumetric 3 Tesla brain Magnetic Resonance Imaging (MRI) to investigate anatomical features including volumetry and structural connectivity. Demographic and clinical data will be also collected. Then, every participant will be treated with a session of TPS for four weeks. Both MCI and AD will be divided into two different comparable groups of treatment: real TPS (treated) and placebo TPS (sham-treated). At 1-month and at 8-month follow-up visits, all subjects will undergo neuropsychological, high-density EEG and MRI evaluations.
TPS has previously been evaluated for its efficacy in improving cognition in AD patients. As a novelty, this proposal will consider whether TPS may be a potential treatment also for MCI stage. Additionally, this non-invasive technique will be assessed for its potential positive impact on functional connectivity and anatomical measurements.
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Being tested
- Transcranial pulse stimulation (TPS)
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial pulse stimulation (TPS)Device
All patients will receive either real TPS or sham treatment once a day for five days/weekly for four weeks. Each daily TPS session takes approximately 30 minutes. TPS produces single ultrashort pulses with a frequency spectrum ranging from 1 to 8 Hz. Ultrasound pulses will be applied using a NEUROLITH TPS generator. Technical parameters will be set as follows: 0.2-0.25 mJ mm2 energy flux density, pulse repetition frequency of 3.5 Hz, 6000 pulses per session. Before the stimulation, individual 3D T1 isometric voxel MRI scans will be performed to allow TPS neuronavigation. Therefore, regions of interest (ROIs) from each participant will be defined by a trained neurologist to target brain areas, as frontal lobe, parietal lobe, precuneus and left/right hippocampus, typically involved in AD pathology.
| Study group | Role | What they receive |
|---|---|---|
| Sham TPS | Sham comparator | A sham TPS is performed once a day for five days/weekly for four weeks in the sham group. Each daily TPS session takes about 30 minutes. Receives: Device: Transcranial pulse stimulation (TPS) |
| Real TPS | Experimental | A real TPS is performed once a day for five days/weekly for four weeks in the sham group. Each daily TPS session takes about 30 minutes. Receives: Device: Transcranial pulse stimulation (TPS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Episodic Memory Score (EMS)
The stability/improvement of the memory profile in MCI and mild AD patients subjected to TPS treatment, in the short and long term, will be evaluated using Episodic Memory Score (EMS). (integrated neuropsychological assessment tool designed to evaluate verbal and visual episodic memory and predict the progression from amnestic Mild Cognitive Impairment (aMCI) to Alzheimer's disease) Range: from 4 (worst performance) to 12 (best performance).
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Secondary outcomes (11)
EEG functional connectivity
To evaluate the changes in electrophysiological indices of functional connectivity, applying graph theory, in MCI and mild AD patients treated with real TPS compared to those treated with placebo TPS, both in the short and long term; Furthermore, identify neurophysiological measurements capable of predicting a positive response to treatment.
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Cortical thickness
To evaluate the changes in cortical thickness using radiological data, in the MCI and mild AD groups treated with real TPS compared to the MCI and mild AD groups treated with placebo, both in the short and long term.
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Structural connectivity
To evaluate the changes structural connectivity, using radiological data, in the MCI and mild AD groups treated with real TPS compared to the MCI and mild AD groups treated with placebo, both in the short and long term.
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Rey Auditory Verbal Learning Test (RAVLT)
neuropsychological tests
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Rey Osterrieth Complex Figure (ROCF) - copy and recall tasks
neuropsychological tests
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Episodic Memory Score (EMS)
neuropsychological tests
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Digit Span forward and backward
neuropsychological tests
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Trail Making Test (TMT), part A and B
neuropsychological tests
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Phonemic and semantic verbal fluency
neuropsychological tests
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Object namnaming task
neuropsychological tests
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Neuropsychiatric Inventory Questionnaire (NPI)
neuropsychological tests
Measured: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2026
- Study start30 May 2024
- Primary completion31 Mar 2026
- Study completion30 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele Roma
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07883148
- Sponsor's protocol ID
- 94/SR/24
- Acronym
- TPSAlz
- Status last verified
- Oct 2026
- First submitted
- 26 Mar 2025
- Last updated
- 20 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Transcranial Pulse Stimulation on Functional and Structural Brain Connectivity in Mild Cognitive Impairment and in the Early Stages of Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT07883148
- Acronym / sponsor ID
- TPSAlz / 94/SR/24
- Conditions
- Alzheimer Disease, Mild Cognitive Impairment
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- IRCCS San Raffaele RomaUniversity, hospital or other
- Study start
- 30 May 2024 (actual)
- Primary completion
- 31 Mar 2026 (actual)
- Study completion
- 30 Sep 2026 (actual)
- First posted
- 20 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this study is to evaluate the effects of transcranial pulse stimulation (TPS) in modulating cognitive functions as well as structural and functional connectivity in individuals with mild cognitive impairment and early Alzheimer's disease. The main outcome measure is to confirm whether TPS may be considered as an effective treatment to improve memory in a large cohort of participants and investigating its long-term effects. Then, secondary measurements are to evaluate if TPS may induce neuronal connectivity changes and may confirm previous results exploring whether this innovative technique may induce, in a long and short-term period, possible effects on cortical atrophy and structural connectivity. An additional outcomes is to evaluate if TPS may have a positive impact on global cognitive functioning and behavioral profile.
Detailed description
The incidence of dementia is increasing worldwide, and great research efforts have been pointing towards novel therapeutic strategies to slow down or treat the occurrence of dementia.
Among non-invasive brain stimulation techniques, transcranial pulse stimulation (TPS) has recently demonstrated its potential in modulating brain functions and improving cognitive performances in Alzheimer's disease (AD) patients. Little is known on its effect on brain network organization/plasticity, particularly in prodromal stages of AD, such as Mild Cognitive Impairment (MCI). The proposal aims to evaluate whether TPS treatment may show positive effects on cognition, neuronal plasticity, and anatomical patterns in MCI due to AD and AD.
In the present placebo-controlled study, at least 26 individuals with MCI due to AD and 26 with AD will be recruited. These two groups will be matched by age, gender and years of education.
The data collection will be performed at baseline, at 1-month follow-up and at 8-month follow-up. At the baseline, all subjects will perform a complete neuropsychological assessment to evaluate cognitive functions, a high-density electroencephalogram (EEG) recording (128 channel) for the evaluation of the brain connectivity through graph theory indices, and a volumetric 3 Tesla brain Magnetic Resonance Imaging (MRI) to investigate anatomical features including volumetry and structural connectivity. Demographic and clinical data will be also collected. Then, every participant will be treated with a session of TPS for four weeks. Both MCI and AD will be divided into two different comparable groups of treatment: real TPS (treated) and placebo TPS (sham-treated). At 1-month and at 8-month follow-up visits, all subjects will undergo neuropsychological, high-density EEG and MRI evaluations.
TPS has previously been evaluated for its efficacy in improving cognition in AD patients. As a novelty, this proposal will consider whether TPS may be a potential treatment also for MCI stage. Additionally, this non-invasive technique will be assessed for its potential positive impact on functional connectivity and anatomical measurements.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sham TPS | Sham comparator | Device: Transcranial pulse stimulation (TPS)A sham TPS is performed once a day for five days/weekly for four weeks in the sham group. Each daily TPS session takes about 30 minutes. |
| Real TPS | Experimental | Device: Transcranial pulse stimulation (TPS)A real TPS is performed once a day for five days/weekly for four weeks in the sham group. Each daily TPS session takes about 30 minutes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Individuals aged ≥18 years; if women, in menopause since at least 2 years;
- fulfilling the diagnostic criteria for MCI due to AD;
- Mini-Mental State Examination (MMSE) score ≥24;
- Clinical Dementia Rating (CDR) ≤0.5;
- Stable presence of an informant family member;
Key exclusion criteria (7 listed)
- Individuals with comorbidities which may interfere with cognitive status (e.g., previous stroke, normal pressure, hydrocephalus, alcohol abuse, brain tumor or brain metastasis);
- Previous medical history positive for psychiatric diseases (except for a recent onset of depression or other behavioral disturbances);
- Treatments which may interfere with cognitive status;
- Blood clotting disorders, epilepsy, and corticosteroid treatment in the last 6 weeks;
- Any contraindication to TPS;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial pulse stimulation (TPS)All patients will receive either real TPS or sham treatment once a day for five days/weekly for four weeks. Each daily TPS session takes approximately 30 minutes. TPS produces single ultrashort pulses with a frequency spectrum ranging from 1 to 8 Hz. Ultrasound pulses will be applied using a NEUROLITH TPS generator. Technical parameters will be set as follows: 0.2-0.25 mJ mm2 energy flux density, pulse repetition frequency of 3.5 Hz, 6000 pulses per session. Before the stimulation, individual 3D T1 isometric voxel MRI scans will be performed to allow TPS neuronavigation. Therefore, regions of interest (ROIs) from each participant will be defined by a trained neurologist to target brain areas, as frontal lobe, parietal lobe, precuneus and left/right hippocampus, typically involved in AD pathology. | Device | Real TPS, Sham TPS |
Primary outcome
Episodic Memory Score (EMS)
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
The stability/improvement of the memory profile in MCI and mild AD patients subjected to TPS treatment, in the short and long term, will be evaluated using Episodic Memory Score (EMS). (integrated neuropsychological assessment tool designed to evaluate verbal and visual episodic memory and predict the progression from amnestic Mild Cognitive Impairment (aMCI) to Alzheimer's disease) Range: from 4 (worst performance) to 12 (best performance).
11 secondary outcomes
EEG functional connectivity
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Cortical thickness
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Structural connectivity
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Rey Auditory Verbal Learning Test (RAVLT)
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Rey Osterrieth Complex Figure (ROCF) - copy and recall tasks
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Episodic Memory Score (EMS)
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Digit Span forward and backward
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Trail Making Test (TMT), part A and B
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Phonemic and semantic verbal fluency
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Object namnaming task
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Neuropsychiatric Inventory Questionnaire (NPI)
Time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial pulse stimulation (TPS) in people with Alzheimer Disease and Mild Cognitive Impairment, run by IRCCS San Raffaele Roma at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Episodic Memory Score (EMS) (time frame: Before TPS sessions, at 1-month follow-up and at 8-months follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.