NCT05454540

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable alzheimer-disease

Timeline
Completed

Started Oct 2018

Longer than P75 for not_applicable alzheimer-disease

Geographic Reach
1 country

2 active sites

Status
completed

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 Start

First participant enrolled

October 1, 2018

Completed
3.7 years until next milestone

First Submitted

Initial submission to the registry

June 16, 2022

Completed
26 days until next milestone

First Posted

Study publicly available on registry

July 12, 2022

Completed
1.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 30, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 30, 2023

Completed
Last Updated

October 18, 2024

Status Verified

July 1, 2022

Enrollment Period

5.2 years

First QC Date

June 16, 2022

Last Update Submit

October 17, 2024

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

  • 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.

    change from baseline to Week 52

Secondary Outcomes (5)

  • Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-Cog)

    change from baseline to Week 52

  • Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL)

    change from baseline to Week 52

  • Neuropsychiatric Inventory (NPI)

    change from baseline to Week 24

  • Frontal Assessment Battery (FAB)

    change from baseline to Week 52

  • Cortical activity (TMS-EEG)

    change from baseline to Week 52

Study Arms (2)

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)

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)

Device: REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION

Interventions

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

SHAM TRANSCRANIAL MAGNETIC STIMULATIONTRANSCRANIAL MAGNETIC STIMULATION

Eligibility Criteria

Age30 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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.

You may not qualify if:

  • 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)
  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Giacomo Koch

Rome, <None>, 00179, Italy

Location

Santa Lucia Foundation

Rome, 00179, Italy

Location

Related Publications (1)

  • 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.

    PMID: 40176122DERIVED

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

Study Officials

  • Giacomo Koch, MD, PHD

    Fondazione Santa Lucia IRCCS

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 16, 2022

First Posted

July 12, 2022

Study Start

October 1, 2018

Primary Completion

November 30, 2023

Study Completion

November 30, 2023

Last Updated

October 18, 2024

Record last verified: 2022-07

Data Sharing

IPD Sharing
Will not share

Locations

IT(2)