Network-based rTMS in Alzheimer's Disease

NCT04263194 | Unknown

• 1 other identifier: GR-2016-02364718
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimer Disease, Late Onset; Alzheimer Disease; Cognitive Deterioration

Keywords

TMS; rTMS; Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Change in ADAS-Cog scale scores

  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 Outcomes (4)

• Change in CANTAB battery scores

  At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)

• Change in brain connectivity

  At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)

• Change in brain plasticity

  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

  At baseline (T0), up to 4 weeks (T1), through study completion, an average of 6 months (T2)

Study Arms (3)

Default Mode Network (DMN)

EXPERIMENTAL

The treatment will consist in the individually tailored stimulation of a DMN node (i.e. left inferior parietal lobe).

Device: rTMS

Central Executive Network (CEN)

EXPERIMENTAL

The treatment will consist in the individually tailored stimulation of a CEN node (i.e. left dorsolateral prefrontal cortex).

Device: rTMS

Placebo

PLACEBO COMPARATOR

The treatment will consist in targeting the upper part of the scalp (i.e. CZ) while using a sham rTMS coil.

Device: Sham rTMS

Interventions

rTMS DEVICE

25 min of high frequency (20 Hz) repetitive TMS applied at 100% of resting motor threshold (rMT).

Central Executive Network (CEN); Default Mode Network (DMN)

Sham rTMS DEVICE

Placebo intervention will consist in the same procedure but using a sham rTMS coil.

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• IRCCS Centro San Giovanni di Dio Fatebenefratelli: lead
• I.R.C.C.S. Fondazione Santa Lucia: collaborator
• Ministero della Salute, Italy: collaborator

Study Sites (1)

IRCCS Centro San Giovanni di Dio Fatebenefratelli

Brescia, Lombardy, 25125, Italy

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Debora Brignani

  IRCCS Centro San Giovanni di Dio Fatebenefratelli

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Debora Brignani

CONTACT

0303501597; dbrignani@fatebenefratelli.eu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: The study will be a double blind trial, i.e. both patients and clinicians involved in the assessment will be blind to treatment allocation.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: After recruitment, patients will be randomized and assigned to one of three rTMS treatments: DMN (N=20), CEN (N=20) or placebo (N=20). The rTMS treatment will consist of 2 phases: an intensive phase and a maintenance phase. The intensive phase will involve 3 weeks of treatment, 5 days per week (15 sessions in total). The maintenance will consist of 1 session of treatment every 2 weeks for 5 months (10 sessions in total). Overall, the patients will undergo 25 sessions of rTMS delivered over 6 months. At baseline (T0), at the end of the intensive phase (T1) and at the end of the maintenance phase (T2) all patients will undergo a clinical and cognitive assessment and a multi-modal imaging data collection.

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: February 10, 2020
• Study Start: March 21, 2019
• Primary Completion: September 21, 2023
• Study Completion: March 21, 2024
• Last Updated: March 13, 2023

Record last verified: 2023-03

Locations

IT (1)