Rehabilitative Trial for the Rescue of Neurophysiological Parameters in Progranulin Deficient Subjects (ReRescuePGR)

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Status: Completed

Conditions: Frontotemporal Dementia; GRN Related Frontotemporal Dementia

Treatments: Device: Sham transcranial direct current stimulation; Device: Anodal transcranial direct current stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT02999282

NP2441

Details and patient eligibility

About

In this randomized, double-blind, sham-controlled study, the investigators will evaluate the effects of frontal and prefrontal anodal transcranial direct current stimulation (tDCS) on neurophysiological parameters of cortical connectivity, assessed by transcranial magnetic stimulation (TMS), in asymptomatic subjects bearing a pathogenic GRN mutation and in symptomatic patients with frontotemporal dementia.

Full description

In this randomized, double-blind, sham-controlled study, the investigators will evaluate the effects of frontal and prefrontal anodal transcranial magnetic stimulation (tDCS) on neurophysiological parameters of cortical connectivity, assessed by transcranial magnetic stimulation (TMS), in asymptomatic subjects bearing a pathogenic GRN mutation and in symptomatic patients with frontotemporal dementia.

All patients will undergo genetic screening for progranulin mutations, a baseline neuropsychological and neurophysiological evaluation, including assessment of short interval intracortical inhibition, intracortical facilitation, short interval intracortical facilitation and long interval intracortical inhibition. Subjects will then be randomized in two groups, one receiving a 10 day (5 days/week for 2 weeks) treatment with anodal frontal and prefrontal anodal tDCS and the other receiving sham stimulation with identical parameters. After the intervention, patients will be reassessed with a neuropsychological and neurophysiological evaluation at 2 weeks, 1 month (only neurophysiological evaluation), 3 months and 6 month after treatment.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: presymptomatic carriers, symptomatic genetic FTD patients, symptomatic sporadic FTD patients.

• Presymptomatic carriers: defined as participants who are known carriers of a pathogenic mutation in the GRN gene, who do not fulfill current criteria for the behavioral variant FTD (bvFTD) (Rascovsky et al. 2011) or for the Primary Progressive Aphasias (PPA) (Gorno-Tempini et al. 2011). All subjects will be genotyped for known pathogenic mutations for FTD (GRN, C9orf72, MAPT, TDP-43) before participation.
• Symptomatic genetic FTD: defined as patients who are known carriers of pathogenic mutation in the GRN gene, fulfilling current clinical criteria for behavioral variant FTD (bvFTD) (Rascovsky et al. 2011) or the agrammatic variant of Primary Progressive Aphasia (avPPA) (Gorno-Tempini et al. 2011).
• Symptomatic sporadic FTD: defined as patients fulfilling current clinical criteria for behavioral variant FTD (bvFTD) (Rascovsky et al. 2011) or the agrammatic variant of Primary Progressive Aphasia (avPPA) (Gorno-Tempini et al. 2011), with a negative screening for pathogenic mutations in known FTD genes (GRN, C9orf72, MAPT, TDP-43). CSF analysis or amyloid PET imaging will be carried out to exclude focal variants of AD.

Exclusion Criteria:

• Cerebrovascular disorders, previous stroke, hydrocephalus, and intra-cranial mass documented by MRI.
• History of traumatic brain injury or other neurological diseases.
• Serious medical illness other than FTD
• History of seizures
• Pregnancy
• Metal implants in the head (except dental fillings)
• Electronic implants (i.e. pace-maker, implanted medical pump)
• Age <18 years

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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70 participants in 4 patient groups

Presymptomatic real tDCS

Experimental group

Description:

Asymptomatic subjects - 10 days anodal transcranial direct current stimulation

Treatment:

Device: Anodal transcranial direct current stimulation

Presymptomatic sham tDCS

Sham Comparator group

Description:

Asymptomatic subjects - 10 days sham transcranial direct current stimulation

Treatment:

Device: Sham transcranial direct current stimulation

Symptomatic real tDCS

Experimental group

Description:

Symptomatic patients - 10 days anodal transcranial direct current stimulation

Treatment:

Device: Anodal transcranial direct current stimulation

Symptomatic sham tDCS

Sham Comparator group

Description:

Symptomatic patients - 10 days sham transcranial direct current stimulation

Treatment:

Device: Sham transcranial direct current stimulation