Repetitive TMS of the Default Mode Network in AD

NCT03778151 | Completed DMC

• 1 other identifier: RC-2018
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

Alzheimer's disease is a global health challenge. Efforts aim at developing an effective treatment able to meet the needs of patients and their families. Thus, the primary aim of this project is to investigate the efficacy of a non-invasive brain stimulation, namely repetitive transcranial magnetic stimulation (rTMS), on cognition in patients with mild 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: an intensive phase and a maintenance phase for a total of six months. 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• Clinical Dementia Rating scale (CDR) sum of boxes

  global cognition

  change from baseline to Week 24

Secondary Outcomes (6)

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

  change from baseline to Week 24

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

  change from baseline to Week 24

• Neuropsychiatric Inventory (NPI)

  change from baseline to Week 24

• Frontal Assessment Battery (FAB)

  change from baseline to Week 24

• Immediate and delayed total recall score from the Rey Auditory Verbal Learning test (RAVLT)

  change from baseline to Week 24

Study Arms (2)

TRANSCRANIAL MAGNETIC STIMULATION

ACTIVE COMPARATOR

repetitive TRANSCRANIAL MAGNETIC STIMULATION (rTMS) will be applied over the precuneus to modulate DMN activity. 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 for a total of 16.000 pulses). The maintenance phase will consist of 1 session of treatment every week for 5 months (21 sessions, 100.800 pulses in total).

Device: REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION

SHAM TRANSCRANIAL MAGNETIC STIMULATION

SHAM COMPARATOR

SHAM TMS will be applied over the precuneus. The SHAM protocol 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 for a total of 16.000 pulses). The maintenance phase will consist of 1 session of treatment every week for 5 months (21 sessions, 100.800 pulses in total).

Device: REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION

Interventions

REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION DEVICE

daily treatment session of REPETITIVE TRANSCRANIAL MAGNETIC STIMULATIO will be applied over precuneus for 20 minutes of consecutive blocks of 20Hz pulses for two seconds followed by 28 seconds of no stimulation.

Also known as: RTMS

SHAM TRANSCRANIAL MAGNETIC STIMULATION; TRANSCRANIAL MAGNETIC STIMULATION

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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) 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

Sponsors & Collaborators

• I.R.C.C.S. Fondazione Santa Lucia: lead

Study Sites (2)

Giacomo Koch

Rome, 00179, Italy

Location

Santa Lucia Foundation

Rome, 00179, Italy

Location

Related Publications (2)

• Koch G, Bonni S, Pellicciari MC, Casula EP, Mancini M, Esposito R, Ponzo V, Picazio S, Di Lorenzo F, Serra L, Motta C, Maiella M, Marra C, Cercignani M, Martorana A, Caltagirone C, Bozzali M. Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer's disease. Neuroimage. 2018 Apr 1;169:302-311. doi: 10.1016/j.neuroimage.2017.12.048. Epub 2017 Dec 19.

  PMID: 29277405 BACKGROUND

• Di Lorenzo F, Ponzo V, Bonni S, Motta C, Negrao Serra PC, Bozzali M, Caltagirone C, Martorana A, Koch G. Long-term potentiation-like cortical plasticity is disrupted in Alzheimer's disease patients independently from age of onset. Ann Neurol. 2016 Aug;80(2):202-10. doi: 10.1002/ana.24695. Epub 2016 Jul 8.

  PMID: 27255833 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Caterina Motta

  Santa Lucia Foundation

  STUDY DIRECTOR

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: PRINCIPAL INVESTIGATOR
• PI Title: Head of Laboratory

Study Record Dates

• First Submitted: December 14, 2018
• First Posted: December 19, 2018
• Study Start: February 1, 2018
• Primary Completion: August 30, 2020
• Study Completion: October 1, 2020
• Last Updated: February 8, 2021

Record last verified: 2021-02

Locations

IT (2)