Alzheimer DiseaseNCT05454540
Repetitive TMS of the Posterior DMN in AD
A study testing REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION in people with Alzheimer Disease, run by I.R.C.C.S. Fondazione Santa Lucia at 2 sites in Italy.
Trial summary
The primary aim of this project is to investigate the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) on cognition in patients with mild to moderate Alzheimer's disease. rTMS is considered a safe, well tolerated and relatively cheap treatment. Read more about this study
- Who is it for?
- Ages 30 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Oct 2018to 30 Nov 2023
- 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 30 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient and the responsible caregiver have signed the Informed Consent Form.
- The patient has probable AD, diagnosed according to NINCDS-ADRDA criteria.
- The patient is a man or woman, aged ≤ 85 years.
- The patient has a CDR total score of 0.5 or 1 (mild to moderate) and MMSE score of 18-26 (inclusive) at Screening.
- Has at least one identified adult caregiver
- The patient has been treated with acetylcholinesterase inhibitor (AChEI), i.e., donepezil, galantamine, or rivastigmine, at the time of Screening
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- for at least 3 months
- The current dosage regimen must have remained stable for ≥ 8 weeks
- It must be planned that the dosage regimen will remain stable throughout participation in the study
- The patient is able to comply with the study procedures in the view of the investigator.
Who cannot join
- Significant neurodegenerative disorder of the central nervous system other than Alzheimer's disease
- Significant intracranial focal or vascular pathology seen on brain MRI scan
- History of seizure (with the exception of febrile seizures in childhood)
- Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR) criteria met for any of the following within specified period:
- Major depressive disorder (current)
- Schizophrenia (lifetime)
Show all 12Show fewer
- Other psychotic disorders, bipolar disorder, or substance (including alcohol) related disorders (within the past 5 years)
- Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging.
- Treatment currently or within 3 months before Baseline with any of the following medications:
- Typical and atypical antipsychotics (i.e. Clozapine, Olanzapine)
- Antiepileptics drugs (i.e. Carbamazepine, Primidone, Pregabalin, Gabapentin)
- Memantine
Trial locations and contacts
2 sites in 1 country.
About this study
Official title: A Randomized Double-blinded Sham-controlled Trial of Precuneus RTMS in Mild to Moderate Alzheimer's Disease Patients.
The primary aim of this project is to investigate the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) on cognition in patients with mild to moderate Alzheimer's disease. rTMS is considered a safe, well tolerated and relatively cheap treatment. The appealing idea of the intervention is to improve memory by directly modulating the activity of precuneus, key area linked to memory impairment. Patients will be treated with rTMS in two phases: a 2-week intensive phase followed by a maintenance phase for a total of 52 weeks. This project aims to provide a valid treatment to slow the worsening of symptoms and improve quality of life for those with Alzheimer's and their caregivers.
Read the detailed description
Detailed Description:
Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by severe disruption of large-scale brain networks connectivity. AD pathophysiology has been mainly associated with a breakdown of the Default Mode Network (DMN) and with a structural disconnection of parietal nodes. It has been shown that the precuneus (PC), a central hub of the DMN, is involved in successful episodic memory retrieval, working as a key area of the network activated by recognition memory. Recent anatomical works have shown that medial parietal regions are interconnected with the medial temporal region, which is implicated in memory retrieval. In particular, the PC was identified as a region demonstrating strong functional interconnectivity with the hippocampal formation. This is of particular relevance because PC is altered in AD. At early clinical stages of AD, PC is selectively vulnerable to early amyloid deposition, and plays a critical role in the conversion towards dementia.
Hypothesis: a novel therapeutic intervention for AD is repetitive Transcranial Magnetic Stimulation (rTMS). rTMS is a non- invasive approach that can be used to induce long lasting modulation of specific brain functions, inducing neuroplastic changes not only in the cortical site of stimulation, but also in remote interconnected areas. In a recent double blind randomized cross-over clinical pilot study, the investigators found that a two-week course of daily high-frequency rTMS (20 Hz) treatment targeting the DMN (Stimulation site: PC) was able to induce an improvement in episodic memory compared to placebo. Indeed, TMS-EEG measurements showed that rTMS treatment, applied over the DMN, was capable to modulate the cortical activity in both the targeted areas (PC) as well as in functional connected regions of the DMN.
Specific aims: to investigate clinical efficacy and safety of DMN rTMS applied during 12 months in mild to moderate AD patients. To provide novel evidence that non-invasive treatment of network dysfunction, through stimulation of the PC, will represent an effective strategy to enhance cognitive functions and lead to substantial slowing of cognitive and functional decline in patients with mild AD. The findings yielded by the present project will have a potential strong impact on clinical practice of AD patients. Since rTMS is well tolerated and relatively low-priced, a positive result could lead to a fast application of the present proposal to the clinical experience. If successful, the proposed project will provide support for a novel treatment for cognitive dysfunction in AD patients.
- Conditions
- Alzheimer Disease
- Being tested
- REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
REPETITIVE TRANSCRANIAL MAGNETIC STIMULATIONDevice
daily treatment session of REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION will be applied over precuneus for 20 minutes of consecutive blocks of 20Hz pulses for two seconds followed by 28 seconds of no stimulation.
Other Name: RTMS
| Study group | Role | What they receive |
|---|---|---|
| TRANSCRANIAL MAGNETIC STIMULATION | Active comparator | repetitive TRANSCRANIAL MAGNETIC STIMULATION (rTMS) will be applied over the precuneus. The rTMS treatment will consist of two phases: an intensive phase and a maintenance phase. The intensive phase will involve 2 weeks of treatment, 5 days per week (10 sessions, 1.600 pulses per day at 20 Hz for a total of 16.000 pulses). The maintenance phase will consist of 1 session of treatment every week for 50 weeks (80.000 pulses) Receives: Device: REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION |
| SHAM TRANSCRANIAL MAGNETIC STIMULATION | Sham comparator | SHAM TMS will be applied over the precuneus. The sham rTMS treatment will consist of two phases: an intensive phase and a maintenance phase. The intensive phase will involve 2 weeks of treatment, 5 days per week (10 sessions, 1.600 pulses per day at 20 Hz for a total of 16.000 pulses). The maintenance phase will consist of 1 session of treatment every week for 50 weeks (80.000 pulses) Receives: Device: REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Dementia Rating scale (CDR) sum of boxes
global cognition and disease severity. The score range from 0-18 with the higher score meaning greater disease severity.
Measured: change from baseline to Week 52
Secondary outcomes (5)
Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)
global cognition. The score range from 0-70 with the higher score meaning greater cognitive impairment.
Measured: change from baseline to Week 52
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
functional activities. The score range from 0-78 with a lower score indicating more severe functional impairment.
Measured: change from baseline to Week 52
Neuropsychiatric Inventory (NPI)
behavioural symptoms. The score range from 0-144 with the higher score meaning more severe behavioural disturbances.
Measured: change from baseline to Week 24
Frontal Assessment Battery (FAB)
frontal lobe functions. The score range from 0-18 with the higher score meaning less frontal cognitive impairment.
Measured: change from baseline to Week 52
Cortical activity (TMS-EEG)
neurophysiological marker
Measured: change from baseline to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2022
- Study start1 Oct 2018
- Primary completion30 Nov 2023
- Study completion30 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- I.R.C.C.S. Fondazione Santa Lucia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giacomo Koch, MD, PHD, Principal investigator, Fondazione Santa Lucia IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05454540
- Sponsor's protocol ID
- Brightfocus: A2019523S
- Status last verified
- Jul 2022
- First submitted
- 16 Jun 2022
- Last updated
- 18 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Koch G, Casula EP, Bonni S, Borghi I, Assogna M, Di Lorenzo F, Esposito R, Maiella M, D'Acunto A, Ferraresi M, Mencarelli L, Pezzopane V, Motta C, Santarnecchi E, Bozzali M, Martorana A. Effects of 52 weeks of precuneus rTMS in Alzheimer's disease patients: a randomized trial. Alzheimers Res Ther. 2025 Apr 2;17(1):69. doi: 10.1186/s13195-025-01709-7.
PubMed 40176122
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-blinded Sham-controlled Trial of Precuneus RTMS in Mild to Moderate Alzheimer's Disease Patients.
- ClinicalTrials.gov ID
- NCT05454540
- Acronym / sponsor ID
- Brightfocus: A2019523S
- Conditions
- Alzheimer Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- I.R.C.C.S. Fondazione Santa LuciaUniversity, hospital or other
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 30 Nov 2023 (actual)
- Study completion
- 30 Nov 2023 (actual)
- First posted
- 12 Jul 2022 (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 primary aim of this project is to investigate the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) on cognition in patients with mild to moderate Alzheimer's disease. rTMS is considered a safe, well tolerated and relatively cheap treatment. The appealing idea of the intervention is to improve memory by directly modulating the activity of precuneus, key area linked to memory impairment. Patients will be treated with rTMS in two phases: a 2-week intensive phase followed by a maintenance phase for a total of 52 weeks. This project aims to provide a valid treatment to slow the worsening of symptoms and improve quality of life for those with Alzheimer's and their caregivers.
Detailed description
Detailed Description:
Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by severe disruption of large-scale brain networks connectivity. AD pathophysiology has been mainly associated with a breakdown of the Default Mode Network (DMN) and with a structural disconnection of parietal nodes. It has been shown that the precuneus (PC), a central hub of the DMN, is involved in successful episodic memory retrieval, working as a key area of the network activated by recognition memory. Recent anatomical works have shown that medial parietal regions are interconnected with the medial temporal region, which is implicated in memory retrieval. In particular, the PC was identified as a region demonstrating strong functional interconnectivity with the hippocampal formation. This is of particular relevance because PC is altered in AD. At early clinical stages of AD, PC is selectively vulnerable to early amyloid deposition, and plays a critical role in the conversion towards dementia.
Hypothesis: a novel therapeutic intervention for AD is repetitive Transcranial Magnetic Stimulation (rTMS). rTMS is a non- invasive approach that can be used to induce long lasting modulation of specific brain functions, inducing neuroplastic changes not only in the cortical site of stimulation, but also in remote interconnected areas. In a recent double blind randomized cross-over clinical pilot study, the investigators found that a two-week course of daily high-frequency rTMS (20 Hz) treatment targeting the DMN (Stimulation site: PC) was able to induce an improvement in episodic memory compared to placebo. Indeed, TMS-EEG measurements showed that rTMS treatment, applied over the DMN, was capable to modulate the cortical activity in both the targeted areas (PC) as well as in functional connected regions of the DMN.
Specific aims: to investigate clinical efficacy and safety of DMN rTMS applied during 12 months in mild to moderate AD patients. To provide novel evidence that non-invasive treatment of network dysfunction, through stimulation of the PC, will represent an effective strategy to enhance cognitive functions and lead to substantial slowing of cognitive and functional decline in patients with mild AD. The findings yielded by the present project will have a potential strong impact on clinical practice of AD patients. Since rTMS is well tolerated and relatively low-priced, a positive result could lead to a fast application of the present proposal to the clinical experience. If successful, the proposed project will provide support for a novel treatment for cognitive dysfunction in AD patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TRANSCRANIAL MAGNETIC STIMULATION | Active comparator | Device: REPETITIVE TRANSCRANIAL MAGNETIC STIMULATIONrepetitive TRANSCRANIAL MAGNETIC STIMULATION (rTMS) will be applied over the precuneus. The rTMS treatment will consist of two phases: an intensive phase and a maintenance phase. The intensive phase will involve 2 weeks of treatment, 5 days per week (10 sessions, 1.600 pulses per day at 20 Hz for a total of 16.000 pulses). The maintenance phase will consist of 1 session of treatment every week for 50 weeks (80.000 pulses) |
| SHAM TRANSCRANIAL MAGNETIC STIMULATION | Sham comparator | Device: REPETITIVE TRANSCRANIAL MAGNETIC STIMULATIONSHAM TMS will be applied over the precuneus. The sham rTMS treatment will consist of two phases: an intensive phase and a maintenance phase. The intensive phase will involve 2 weeks of treatment, 5 days per week (10 sessions, 1.600 pulses per day at 20 Hz for a total of 16.000 pulses). The maintenance phase will consist of 1 session of treatment every week for 50 weeks (80.000 pulses) |
Who may qualify
- Ages
- 30 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- The patient and the responsible caregiver have signed the Informed Consent Form.
- The patient has probable AD, diagnosed according to NINCDS-ADRDA criteria.
- The patient is a man or woman, aged ≤ 85 years.
- The patient has a CDR total score of 0.5 or 1 (mild to moderate) and MMSE score of 18-26 (inclusive) at Screening.
- Has at least one identified adult caregiver
Key exclusion criteria (12 listed)
- Significant neurodegenerative disorder of the central nervous system other than Alzheimer's disease
- Significant intracranial focal or vascular pathology seen on brain MRI scan
- History of seizure (with the exception of febrile seizures in childhood)
- Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM IV-TR) criteria met for any of the following within specified period:
- Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging.
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 |
|---|---|---|
| REPETITIVE TRANSCRANIAL MAGNETIC STIMULATIONdaily treatment session of REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION will be applied over precuneus for 20 minutes of consecutive blocks of 20Hz pulses for two seconds followed by 28 seconds of no stimulation. Other Name: RTMS | Device | SHAM TRANSCRANIAL MAGNETIC STIMULATION, TRANSCRANIAL MAGNETIC STIMULATION |
Primary outcome
Clinical Dementia Rating scale (CDR) sum of boxes
Time frame: change from baseline to Week 52
global cognition and disease severity. The score range from 0-18 with the higher score meaning greater disease severity.
5 secondary outcomes
Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)
Time frame: change from baseline to Week 52
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)
Time frame: change from baseline to Week 52
Neuropsychiatric Inventory (NPI)
Time frame: change from baseline to Week 24
Frontal Assessment Battery (FAB)
Time frame: change from baseline to Week 52
Cortical activity (TMS-EEG)
Time frame: change from baseline to Week 52
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 18 Oct 2024.
- Derived from this study: PubMed 40176122Koch G, Casula EP, Bonni S, Borghi I, Assogna M, Di Lorenzo F, Esposito R, Maiella M, D'Acunto A, Ferraresi M, Mencarelli L, Pezzopane V, Motta C, Santarnecchi E, Bozzali M, Martorana A. Effects of 52 weeks of precuneus rTMS in Alzheimer's disease patients: a randomized trial. Alzheimers Res Ther. 2025 Apr 2;17(1):69. doi: 10.1186/s13195-025-01709-7.
- Individual participant dataSharing planned: No
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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.
Giacomo Koch, MD, PHD principal investigator
Fondazione Santa Lucia IRCCS
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION in people with Alzheimer Disease, run by I.R.C.C.S. Fondazione Santa Lucia at 2 sites 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 10 inclusion and 12 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 18 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Clinical Dementia Rating scale (CDR) sum of boxes (time frame: change from baseline to Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05454540, which also lists 1 linked publication.
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 18 Oct 2024.