Alzheimer DiseaseTMSLANCT07036328
Transcranial Magnetic Stimulation to Slow Down Cognitive Decline in Alzheimer's Disease
A study testing repetitive transcranial magnetic stimulation in people with Alzheimer Disease and Alzheimer Disease, Early Onset, run by Willem de Haan at 1 site in Netherlands.
Trial summary
New amyloid-targeting drugs for Alzheimer's disease (AD) offer minimal or unclear efficacy and often cause adverse events, highlighting the need for new therapies. In recent years, repetitive transcranial magnetic stimulation (rTMS) has shown increasing success. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease, Alzheimer Disease, Early Onset
- 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
- 55 participants
- Where
- 1 siteNetherlands
- Study dates
- 7 Apr 2025to Jul 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Biomarker-supported Alzheimer's disease (abnormal CSF p-tau/Aβ42 ratio of > 0.023 or amyloid PET positive).
- Between 50 and 85 years old.
- Clinical Dementia Rating (CDR) score of 0.5 or 1.
- Mini-Mental State Examination (MMSE) score between 18 and 27.
- Presence of a caregiver.
Who cannot join
- Medical history of neurodegenerative diseases other than AD, stroke, or epilepsy.
- Severe psychiatric dysregulation, hampering successful study participation and leading to possible cognitive impairment. Eligibility for participation will be based on clinical evaluation by an expert neurologist and/or psychiatrist.
- Extensive cerebrovascular damage on MRI classified as Fazekas level 2 or 3. Patients with abnormalities classified as Fazekas level 3 are excluded. For Fazekas level 2, patient's eligibility for participation will be evaluated by an expert neurologist.
- Presence of metal in the head or cranial/thoracic implants, including cochlear implants.
- Cholinesterase inhibitors with unstable dosage in the last 2 months.
- Extreme claustrophobia or metallic objects in or on the body, preventing MRI and MEG examination.
- Previous rTMS treatment (for blinding reasons).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam
Willem de Haan, PhD, 020-444 8548, tmsla@amsterdamumc.nl
About this study
Official title: Transcranial Magnetic Stimulation (TMS) to Slow Down Cognitive Decline in Alzheimer's Disease (AD): TMSLA - a Monocentric Randomized Controlled Trial.
New amyloid-targeting drugs for Alzheimer's disease (AD) offer minimal or unclear efficacy and often cause adverse events, highlighting the need for new therapies. In recent years, repetitive transcranial magnetic stimulation (rTMS) has shown increasing success. A recent randomized, double-blind, sham-controlled, phase 2 demonstrated promising results from a 24-week rTMS treatment protocol targeting the precuneus. This brain region is considered a main hub of the human brain connectome and a prominent area of AD pathology. The results showed stable cognitive performance and increased brain activity in the treatment group, whereas the sham group worsened. A replication study is planned to further investigate the working mechanism of precuneus-rTMS in AD and to improve understanding of its therapeutic potential.
- Conditions
- Alzheimer Disease, Alzheimer Disease, Early Onset
- Being tested
- repetitive transcranial magnetic stimulation, sham 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
20 Hz repetitive transcranial magnetic stimulation targeted at the precuneus
sham repetitive transcranial magnetic stimulationDevice
20 Hz sham repetitive transcranial magnetic stimulation targeted at the precuneus
| Study group | Role | What they receive |
|---|---|---|
| Verum | Experimental | Verum rTMS Receives: Device: repetitive transcranial magnetic stimulation |
| Sham | Sham comparator | sham rTMS Receives: Device: sham repetitive transcranial magnetic stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
CDR - Sum of Boxes
Clinical dementia rating - sum of boxes
Measured: from enrollment to 3 month follow-up
Secondary outcomes (15)
Magnetoencephalography (MEG): Spectral analysis
Power spectral density (µV²/Hz) computed for different frequency bands .
Measured: from baseline to week 24 (post-treatment)
Cerebrospinal fluid (CSF) biomarkers
Cerebrospinal fluid (CSF) biomarkers are typically reported in picograms per milliliter (pg/mL). This applies to:
Amyloid-beta (Aβ₁-₄₂): pg/mL Total tau (t-tau): pg/mL Phosphorylated tau (p-tau, e.g., p-tau181): pg/mL
Measured: from baseline to week 24 (post-treatment)
Neuropsychological evaluation: Trail Making Test
Assesses visual attention, processing speed, and task switching. Unit: Seconds (completion time)
Measured: from baseline to week 24 (post-treatment)
Amsterdam instrumental activities of daily living questionnaire (AmsterdamiADL);
The Amsterdam Instrumental Activities of Daily Living (A-IADL) Questionnaire is a validated tool that assesses cognitive functioning through everyday tasks, with scores ranging from approximately 20 (severe impairment) to 70 (no impairment).
Measured: baseline to 3 month follow-up
Mini mental state examination (MMSE)
The mini-mental state examination (MMSE) test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. Higher is better.
Measured: baseline to 3-month follow up.
Neuropsychiatric Inventory Questionnaire (NPI-Q)
The Neuropsychiatric Inventory Questionnaire (NPI-Q) is a brief, informant-based tool that assesses 12 neuropsychiatric symptoms in dementia, with total severity scores ranging from 0 to 36 and distress scores from 0 to 60.
Measured: baseline to 3 month follow up
Quick Inventory of Depressive Symptomatology (QIDS)
The Quick Inventory of Depressive Symptomatology (QIDS) is a clinician-rated tool that measures the severity of depressive symptoms, with total scores ranging from 0 (no depression) to 27 (severe depression).
Measured: baseline to 3-month follow up
Magnetoencephalography (MEG): Corrected Amplitude Envelope Correlation (AEC-c)
Correlation of the amplitude envelopes of band-pass filtered signals, corrected for signal leakage.
Measured: From baseline to week 24 (post-treatment)
Magnetoencephalography (MEG): Phase Lag Index (PLI)
A measure of phase synchronization that is robust to volume conduction.
Measured: baseline to week 24 (post-treatment)
Magnetoencephalography (MEG): Joint Permutation Entropy (JPE)
A nonlinear measure of signal complexity and diversity in joint time series.
Measured: baseline to week 24 (post-treatment)
Neuropsychological evaluation: Verbal Fluency Test
Measures verbal production and executive functioning.
Phonemic fluency (letters D, A, T) Unit: Number of words per 1 minute
Semantic fluency (animals) Unit: Number of words per 1 minute
Measured: baseline to week 24 (post-treatment)
Neuropsychological evaluation: Visual Association Test (VAT)
Detects signs of anterograde amnesia through object-pair associations. Unit: Number of correct associations (maximum score: 12)
Measured: baseline to week 24 (post-treatment)
Neuropsychological evaluation: Stroop Color and Word Test
Evaluates cognitive flexibility, inhibition, and processing speed. Unit: Seconds (per condition), Errors (count)
Measured: baseline to week 24 (post-treament)
Neuropsychological evaluation: WAIS-III Digit Span (Forward and Backward)
Assesses attention and verbal working memory. Unit: Span length (maximum correctly repeated digit sequences)
Measured: baseline to week 24 (post-treatment)
Neuropsychological evaluation: Rey Auditory Verbal Learning Test (RAVLT)
Evaluates verbal learning and declarative memory.
Immediate recall (Trials I-V) Unit: Total number of words recalled
Delayed recall Unit: Number of words recalled
Recognition Unit: Number of correct recognitions
Measured: baseling to week 24 (post-treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2025
- Study start7 Apr 2025
- Primary completionJan 2028 (estimated)
- Study completionJul 2028 (estimated)
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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Willem de Haan
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Willem de Haan, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07036328
- Sponsor's protocol ID
- 2024.0870
- Acronym
- TMSLA
- Status last verified
- May 2025
- First submitted
- 24 Apr 2025
- Last updated
- 12 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The individual participant data will be made available upon reasonable request to the corresponding author in consultation with the data protection officer
Publications
Koch G, Casula EP, Bonni S, Borghi I, Assogna M, Minei M, Pellicciari MC, Motta C, D'Acunto A, Porrazzini F, Maiella M, Ferrari C, Caltagirone C, Santarnecchi E, Bozzali M, Martorana A. Precuneus magnetic stimulation for Alzheimer's disease: a randomized, sham-controlled trial. Brain. 2022 Nov 21;145(11):3776-3786. doi: 10.1093/brain/awac285.
PubMed 36281767
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Magnetic Stimulation (TMS) to Slow Down Cognitive Decline in Alzheimer's Disease (AD): TMSLA - a Monocentric Randomized Controlled Trial.
- ClinicalTrials.gov ID
- NCT07036328
- Acronym / sponsor ID
- TMSLA / 2024.0870
- Conditions
- Alzheimer Disease, Alzheimer Disease, Early Onset
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Willem de HaanUniversity, hospital or other
- Study start
- 7 Apr 2025 (actual)
- Primary completion
- Jan 2028 (estimated)
- Study completion
- Jul 2028 (estimated)
- First posted
- 25 Jun 2025 (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.
New amyloid-targeting drugs for Alzheimer's disease (AD) offer minimal or unclear efficacy and often cause adverse events, highlighting the need for new therapies. In recent years, repetitive transcranial magnetic stimulation (rTMS) has shown increasing success. A recent randomized, double-blind, sham-controlled, phase 2 demonstrated promising results from a 24-week rTMS treatment protocol targeting the precuneus. This brain region is considered a main hub of the human brain connectome and a prominent area of AD pathology. The results showed stable cognitive performance and increased brain activity in the treatment group, whereas the sham group worsened. A replication study is planned to further investigate the working mechanism of precuneus-rTMS in AD and to improve understanding of its therapeutic potential.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Verum | Experimental | Device: repetitive transcranial magnetic stimulationVerum rTMS |
| Sham | Sham comparator | Device: sham repetitive transcranial magnetic stimulationsham rTMS |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Biomarker-supported Alzheimer's disease (abnormal CSF p-tau/Aβ42 ratio of > 0.023 or amyloid PET positive).
- Between 50 and 85 years old.
- Clinical Dementia Rating (CDR) score of 0.5 or 1.
- Mini-Mental State Examination (MMSE) score between 18 and 27.
- Presence of a caregiver.
Key exclusion criteria (7 listed)
- Medical history of neurodegenerative diseases other than AD, stroke, or epilepsy.
- Severe psychiatric dysregulation, hampering successful study participation and leading to possible cognitive impairment. Eligibility for participation will be based on clinical evaluation by an expert neurologist and/or psychiatrist.
- Extensive cerebrovascular damage on MRI classified as Fazekas level 2 or 3. Patients with abnormalities classified as Fazekas level 3 are excluded. For Fazekas level 2, patient's eligibility for participation will be evaluated by an expert neurologist.
- Presence of metal in the head or cranial/thoracic implants, including cochlear implants.
- Cholinesterase inhibitors with unstable dosage in the last 2 months.
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 stimulation20 Hz repetitive transcranial magnetic stimulation targeted at the precuneus | Device | Verum |
| sham repetitive transcranial magnetic stimulation20 Hz sham repetitive transcranial magnetic stimulation targeted at the precuneus | Device | Sham |
Primary outcome
CDR - Sum of Boxes
Time frame: from enrollment to 3 month follow-up
Clinical dementia rating - sum of boxes
15 secondary outcomes
Magnetoencephalography (MEG): Spectral analysis
Time frame: from baseline to week 24 (post-treatment)
Cerebrospinal fluid (CSF) biomarkers
Time frame: from baseline to week 24 (post-treatment)
Neuropsychological evaluation: Trail Making Test
Time frame: from baseline to week 24 (post-treatment)
Amsterdam instrumental activities of daily living questionnaire (AmsterdamiADL);
Time frame: baseline to 3 month follow-up
Mini mental state examination (MMSE)
Time frame: baseline to 3-month follow up.
Neuropsychiatric Inventory Questionnaire (NPI-Q)
Time frame: baseline to 3 month follow up
Quick Inventory of Depressive Symptomatology (QIDS)
Time frame: baseline to 3-month follow up
Magnetoencephalography (MEG): Corrected Amplitude Envelope Correlation (AEC-c)
Time frame: From baseline to week 24 (post-treatment)
Magnetoencephalography (MEG): Phase Lag Index (PLI)
Time frame: baseline to week 24 (post-treatment)
Magnetoencephalography (MEG): Joint Permutation Entropy (JPE)
Time frame: baseline to week 24 (post-treatment)
Neuropsychological evaluation: Verbal Fluency Test
Time frame: baseline to week 24 (post-treatment)
Neuropsychological evaluation: Visual Association Test (VAT)
Time frame: baseline to week 24 (post-treatment)
Neuropsychological evaluation: Stroop Color and Word Test
Time frame: baseline to week 24 (post-treament)
Neuropsychological evaluation: WAIS-III Digit Span (Forward and Backward)
Time frame: baseline to week 24 (post-treatment)
Neuropsychological evaluation: Rey Auditory Verbal Learning Test (RAVLT)
Time frame: baseling to week 24 (post-treatment)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Background: PubMed 36281767Koch G, Casula EP, Bonni S, Borghi I, Assogna M, Minei M, Pellicciari MC, Motta C, D'Acunto A, Porrazzini F, Maiella M, Ferrari C, Caltagirone C, Santarnecchi E, Bozzali M, Martorana A. Precuneus magnetic stimulation for Alzheimer's disease: a randomized, sham-controlled trial. Brain. 2022 Nov 21;145(11):3776-3786. doi: 10.1093/brain/awac285.
- Individual participant dataSharing planned: Yes. The individual participant data will be made available upon reasonable request to the corresponding author in consultation with the data protection officer
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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.
1 site 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 and Alzheimer Disease, Early Onset, run by Willem de Haan at 1 site in Netherlands.
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 5 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: looking for participants now, as of the sponsor's last update on 12 May 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 Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Willem De Haan, PhD (020-444 8548, w.dehaan@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CDR - Sum of Boxes (time frame: from enrollment to 3 month follow-up). 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 NCT07036328, 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 12 May 2026.