Personalized Repetitive Transcranial Magnetic Stimulation (rTMS) in Cognitive Fluctuations of Dementia With Lewy Bodies (DLB): Proof of Concept

NCT05138588 | Recruiting

• 1 other identifier: 8238
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The present study is a monocentric, therapeutic clinical trial involving forty patients diagnosed with Dementia with Lewy Bodies (DLB). The aim of this clinical trial is to evaluate the feasibility and relevance of repetitive transcranial magnetic stimulation (rTMS); a non-invasive neuromodulation technique, with a main emphasis on the evaluation of the outcome on cognitive fluctuations. For this purpose, we will compare two distinct rTMS conditions (control and experimental) in a pre-post rTMS setting. The experimental condition will be targeting the insular cortex which has been shown to be affected at prodromal DLB stages, in the form of decreased grey matter concentration and a decreased regional Cerebral Blood Flow (rCBF hypoperfusion) \[Blanc et al., 2015 ; Roquet et al., 2016 ; Roquet et al., 2017\]. Furthermore, these insular alterations are correlated to cognitive fluctuations \[Chabran et al., 2020\]. In DLB, cognitive fluctuations are particularly pervasive and manifest in the form of alertness alterations and modifications of arousal states. Participants will repeatedly undergo a series of clinical and cognitive assessments in addition to several neuroimaging examinations, namely multimodal Magnetic Resonance Imaging (MRI) and electroencephalogram (EEG) recordings, in order to evaluate potential physiological modifications and clinical changes of symptoms, pre-/post-rTMS.

Conditions

Dementia With Lewy Bodies Diagnosis; Significant Cognitive Fluctuations in DLB

Keywords

rTMS; arousal; DLB; fluctuations; insula

Outcome Measures

Primary Outcomes (2)

• Electroencephalogram measures

  The primary endpoint will be the comparison of the intensity of fluctuations in arousal level

  Primary outcome measures will be realized one week before each rTMS stimulation phase.

• Electroencephalogram measures

  The primary endpoint will be the comparison of the intensity of fluctuations in arousal level

  Primary outcome measures will be realized one week after each rTMS stimulation phase.

Study Arms (2)

VERUM

EXPERIMENTAL

In the "verum" experimental condition, participants will receive the experimental rTMS stimulation sessions, meaning the rTMS sessions targeting the insular cortex, taking into account the insular hypoperfusion (through MRI images) of each patient.

Device: rTMS

CONTROL

SHAM COMPARATOR

In the "control" experimental condition, participants will receive the control rTMS stimulation sessions, meaning the rTMS sessions will target the occipital cortex.

Device: rTMS

Interventions

rTMS DEVICE

For each subject, a verum condition and a control condition will be programmed. We will use the QPS-5 method (4 pulses, Inter-Stimulation Interval; ISI: 5 seconds).

Also known as: Repetitive Magnetic Transcranial Stimulation is a non-invasive neuromodulation technique based on the principle of electromagnetic induction.

CONTROL; VERUM

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patient aged ≥ 45 years
• Enrolled in a social health insurance scheme
• Diagnosed with probable DLB according to McKeith et al. criteria, 2017, or McKeith et al. 2020 criteria for the prodromal stage
• A Mini Mental State Examination (MMSE; Folstein et al., 1983) score ≥ to 18 in the last 6 months (prodromal stage or a major neurocognitive disorder (dementia syndrome) at moderate stage)
• Presence of clinically significant cognitive fluctuations
• Caregivers of eligible patients do have to be able to stay with the patient for at least 4 hours a day, 3 days a week, and have to be able to provide requested information and accompany the patient to the certain visits.
• The patient must be able to understand the objectives and risks of the study and has to be able to give dated and signed informed consent. In the case of a designed guardian or curator, the guardian or curator will sign the consent.
• For women of childbearing age, effective contraception throughout the study is required

You may not qualify if:

• History of generalized seizures (epilepsy)
• Pharmacological treatment for cognitive fluctuations in DLB with dose modifications that have taken place less than 2 months before the first visit of the protocol (anticholinesterase and neuroleptics)
• Anti-epileptic drug treatment "Keppra" (Levetiracetam)
• History of psychosis or severe depression unrelated to DLB
• History of brain surgery (tumour removal, electrode implantation, certain strokes as judged by the investigator, oedema...)
• Patients with any contraindication for MRI scans (claustrophobia, pacemaker, cochlear implant, mechanical heart valve, metallic prostheses, neurostimulators, other non-removably implanted electronic medical devices etc.)
• Subject unable to understand the aims and risks of the study and patients unable to give full informed consent
• Having a MMSE score \< to 18 in the last 6 months (prodromal stage or mild to moderate dementia)
• Patients in an emergency or life-threatening situation
• Patients under court protection
• Pregnancy
• Breastfeeding

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67000, France

RECRUITING

Study Officials

• Frédéric BLANC

  Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fréderic BLANC

CONTACT

03 88 11 58 58; f.blanc@unistra.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All investigators, participants, care providers and outcome assessors will be blinded, with the exception of the investigator programming the stimulation sequences and the nurses administrating the rTMS sequences. For the investigators, the unblinding and the taking of knowledge of the subjects in each group will take place after the end of any experimental run, during the data processing phase. In the event of serious adverse events, the unblinding will be carried out before the end of the research. For participants, the unblinding will take place at the end of the last follow-up visit of the study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: December 1, 2021
• Study Start: February 2, 2022
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)