Network-based rTMS in Alzheimer's Disease

March 10, 2023 updated by: Debora Brignani, IRCCS Centro San Giovanni di Dio Fatebenefratelli

Novel Tailored Network-based rTMS Treatments in Alzheimer's Disease: an Integrated Multiimaging Approach

Severe alterations of brain networks connectivity have been described in Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained evidence as an effective tool to modulate brain networks connectivity, leading to a recovery or reorganization of both local and remote brain regions functionally connected to the stimulated area. The investogators propose an innovative tailored network-based rTMS treatment to ameliorate cognitive symptoms in mild AD, through the boosting of connectivity within brain networks affected by AD pathophysiology. The combination of the proposed intervention with an integrated multi-modal imaging approach will allow to evaluate the neural mechanisms underlying the clinical response to the treatment and to define quantitative markers of clinical impact on AD. If successful, the present proposal would immediately impact on patient's quality of life, with important implications for the time and costs of delivery of rehabilitative services.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Currently, no effective cure is available for Alzheimer's disease (AD). Repetitive Transcranial Magnetic Stimulation (rTMS) has gained increasing attention as a potential treatment for various neurological and psychiatric disorders, but available rTMS studies are flawed by inaccurate anatomical targeting, inadequate sample size, unsatisfactory controls and lacking blindness. To date, the elective target area of rTMS interventions in AD has been the dorsolateral prefrontal cortex (DLPFC), a core area of the Central Executive network (CEN), which plays a key role in regulating executive functions, attention and working memory. While the CEN has recently been described as dysfunctional in AD, AD pathophysiology has been mainly associated with the breakdown of the Default Mode network (DMN) and with structural disconnection of its parietal nodes. The DMN plays a crucial role in episodic memory retrieval and incorporates various brain regions, among which parietal areas are highly connected with the rest of the brain. The present multicenter, double-blind, randomized and placebo-controlled study has the ambition to provide evidence of the efficacy of two tailored network-based rTMS treatments in mild AD, through the enhancement of connectivity of CEN and DMN. Innovative integrated multi-modal imaging investigations will further enrich this proposal allowing to identify quantifiable markers underlying the clinical impact of rTMS on AD.

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Lombardia
      • Brescia, Lombardia, Italy, 25125
        • Recruiting
        • IRCCS Centro San Giovanni di Dio Fatebenefratelli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

55 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Mini-Mental State Examination score >=16, <=24
  • Anti-cholinesterase treatment for at least 3 months prior the start date

Exclusion Criteria:

  • Enrollment in other clinical and pharmacological trials
  • Previous evidence of any other CNS disorder (e.g. epilepsy, infectious diseases, frontotemporal, Parkinson or Pick's disease)
  • History of major psychiatric disorders
  • History of alchol or substance abuse
  • Stress-related skin problems
  • Current consumption of psychiatric medication
  • Presence of metal implants or any implanted electronics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Default Mode Network (DMN)
The treatment will consist in the individually tailored stimulation of a DMN node (i.e. left inferior parietal lobe).
Device: rTMS
25 min of high frequency (20 Hz) repetitive TMS applied at 100% of resting motor threshold (rMT).
Experimental: Central Executive Network (CEN)
The treatment will consist in the individually tailored stimulation of a CEN node (i.e. left dorsolateral prefrontal cortex).
Device: rTMS
25 min of high frequency (20 Hz) repetitive TMS applied at 100% of resting motor threshold (rMT).
Placebo Comparator: Placebo
The treatment will consist in targeting the upper part of the scalp (i.e. CZ) while using a sham rTMS coil.
Device: Sham rTMS
Placebo intervention will consist in the same procedure but using a sham rTMS coil.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in ADAS-Cog scale scores
Time Frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
A brief neuropsychological assessment used to assess the severity of cognitive symptoms of dementia
At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in CANTAB battery scores
Time Frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)

The scores on two tests of CANTAB battery (www.cambridgecognition.com):

  • Change in Associative Learning test (PAL)
  • Change in Spatial Working Memory test (SWM)
At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in brain connectivity
Time Frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
TMS-evoked cortical responses (TEPs) will serve as markers of reactivity of the stimulated area as well as markers of the connectivity between targeted cortex and functionally connected areas underlying DMN or CEN.
At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in brain plasticity
Time Frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
A theta burst stimulation (TBS) protocol will be used to probe plasticity changes
At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
Change in MRI measures of functional and structural connectivity
Time Frame: At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)
At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Collaborators

I.R.C.C.S. Fondazione Santa Lucia
Ministero della Salute, Italy

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2019

Primary Completion (Anticipated)

September 21, 2023

Study Completion (Anticipated)

March 21, 2024

Study Registration Dates

First Submitted

January 30, 2020

First Submitted That Met QC Criteria

February 7, 2020

First Posted (Actual)

February 10, 2020

Study Record Updates

Last Update Posted (Actual)

March 13, 2023

Last Update Submitted That Met QC Criteria

March 10, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GR-2016-02364718

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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