NCT07036328

Brief 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. 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
62

participants targeted

Target at P50-P75 for not_applicable alzheimer-disease

Timeline
26mo left

Started Apr 2025

Typical duration for not_applicable alzheimer-disease

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress34%
Apr 2025Jul 2028

Study Start

First participant enrolled

April 7, 2025

Completed
17 days until next milestone

First Submitted

Initial submission to the registry

April 24, 2025

Completed
2 months until next milestone

First Posted

Study publicly available on registry

June 25, 2025

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2028

Expected
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2028

Last Updated

June 25, 2025

Status Verified

May 1, 2025

Enrollment Period

2.7 years

First QC Date

April 24, 2025

Last Update Submit

June 23, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • CDR - Sum of Boxes

    Clinical dementia rating - sum of boxes

    from enrollment to 3 month follow-up

Secondary Outcomes (15)

  • Magnetoencephalography (MEG): Spectral analysis

    from baseline to week 24 (post-treatment)

  • Cerebrospinal fluid (CSF) biomarkers

    from baseline to week 24 (post-treatment)

  • Neuropsychological evaluation: Trail Making Test

    from baseline to week 24 (post-treatment)

  • Amsterdam instrumental activities of daily living questionnaire (AmsterdamiADL);

    baseline to 3 month follow-up

  • Mini mental state examination (MMSE)

    baseline to 3-month follow up.

  • +10 more secondary outcomes

Study Arms (2)

Verum

EXPERIMENTAL

Verum rTMS

Device: repetitive transcranial magnetic stimulation

Sham

SHAM COMPARATOR

sham rTMS

Device: sham repetitive transcranial magnetic stimulation

Interventions

20 Hz repetitive transcranial magnetic stimulation targeted at the precuneus

Verum

20 Hz sham repetitive transcranial magnetic stimulation targeted at the precuneus

Sham

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 26.
  • Presence of a caregiver.

You may not qualify if:

  • 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).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

Related Publications (1)

  • 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.

    PMID: 36281767BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

DementiaBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative DiseasesNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Central Study Contacts

Willem De Haan, PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

April 24, 2025

First Posted

June 25, 2025

Study Start

April 7, 2025

Primary Completion (Estimated)

January 1, 2028

Study Completion (Estimated)

July 1, 2028

Last Updated

June 25, 2025

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will share

The individual participant data will be made available upon reasonable request to the corresponding author in consultation with the data protection officer

Time Frame
Data will be shared after the study completion indefinitely
Access Criteria
Upon reasonable request

Locations