rTMS for the Treatment of Affective Symptoms in Patients Suffering From Dementia

Study Overview
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Brief Summary
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This is a monocentric prospective, randomized, double-blind placebo-controlled study. It is designed to evaluate the superiority of the rTMS over sham treatment of depressive symptoms in the context of dementia. It is aimed at a population ≥ 65 years old, with affective BPSD. We wish to recruit 44 participants, with an estimated rate of potential drop out of 20%. Patients will be randomly assigned to the sham or rTMS group. The sham stimulation reproduces the procedure in all the steps, has the same duration and differs exclusively by the device setting. After inclusion, both groups will receive 15 sessions distributed over 5 days a week for 3 weeks

Official Title
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Repetitive Transcranial Magnetic Stimulation (rTMS) for the Treatment of Affective Symptoms in Patients Suffering From Dementia: a Randomised Clinical Trial

Conditions
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Behavioral and Psychiatric Symptoms of Dementia

Intervention / Treatment
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* Device: rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent as documented by their and their proxy's signature (Appendix Informed Consent Form) Consent for MRI Age ≥ 65 years Clinical dementia Rating Scale (CDR) ≥ 1 NPI-Q Σ (*Anxiety + * Apathy/Indifference + * Dysphoria/Depression) ≥ 3 Cornell Scale for Depression in Dementia (CSDD) ≥ 10 Exclusion Criteria: History of schizophrenia, bipolar disorder, schizoaffective disorder History of macroscopic stroke. Unstable somatic pathologies Insufficient collaboration for the rTMS procedure Drug freeness or drug adjustment as clinically required is not an exclusion criterion. The proxy refuses to give consent in case of lack of capacity, or in any case where the participant expresses a wish not to participate/continue in the study. Any contraindications to performing an MRI (cf CRF) and rTMS (aneurysm clips or coils, stents in the neck or brain, deep brain stimulators, electrodes to monitor brain activity, metal implants in the ears and eyes, facial tattoos with metallic or magnetically sensitive ink) procedure

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active<br>Magnetic stimulus intensity of 80% of the motor threshold applied at the frequency of 20 Hz over the left DLPFC with a total number of pulses of 1200 / treatment session for a total of 5 sessions /week for 3 consecutive weeks | Device: rTMS<br>* The stimulus intensity will be 80% of the motor threshold and the frequency will be 20 Hz for all patients. The total number of pulses will be 1200 for a single treatment session. We plan a total of 15 sessions distributed over 5 days a week for 3 consecutive weeks.<br>|
| Placebo Comparator: Sham<br>Sham procedure implies the use of a sham coil of exactly the same dimension and appearance as the one used for the effective treatment. This sham coil is made for research purposes by the producing company and used in accordance with the instructions for use, which explicitly mention it (cf. instruction manual page 34: Stimulation Coil DuoMAG 70BFP (70BFP1, 70BFP2), typical use for blinded studies). | Device: rTMS<br>* The stimulus intensity will be 80% of the motor threshold and the frequency will be 20 Hz for all patients. The total number of pulses will be 1200 for a single treatment session. We plan a total of 15 sessions distributed over 5 days a week for 3 consecutive weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cornell Scale for Depression in Dementia (CSDD) | Mood assessment tool | from baseline to day 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal Cognitive Assessment (MOCA) | Cognitive assessment tool | from baseline to day 20 | 
| NPI-Q | Behavioural assessment tool for demented patients | from baseline to day 20 | 
| The ratio of patients who completed the study and drop-outs due to non-compliance | Compliance assessment tool | During all the study period | 
| Possible changes of structural MRI before as compared to after the treatment | quantitative structural MRI protocol allowing for an optimal segmentation - resolution of grey versus white matter including cortical and sub-cortical brain structures. | from baseline to day 20 |