Rehabilitative Trial for the Recovery of Neurophysiological Parameters in Progranulin Mutation Carriers Through the Use of Transcranial Direct Current Stimulation (tDCS)
Overview
- Phase
- N/A
- Intervention
- Not specified
- Conditions
- Frontotemporal Dementia
- Sponsor
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- Change in SICI measurements from Baseline
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Detailed 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.
Investigators
Barbara Borroni
Associated Professor; MD
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Eligibility 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
Outcomes
Primary Outcomes
Change in SICI measurements from Baseline
Time Frame: Baseline - 2 weeks
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of frontal and prefrontal anodal transcranial magnetic stimulation on short interval intracortical inhibition (SICI)
Change in ICF measurements from Baseline
Time Frame: Baseline - 2 weeks
By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of frontal and prefrontal anodal transcranial magnetic stimulation on intracortical facilitation (ICF).
Secondary Outcomes
- Change in SICI measurements from Baseline(Baseline - 1 month - 3 months - 6 months)
- Change in ICF measurements from Baseline(Baseline - 1 month - 3 months - 6 months)
- Change in LICI measurements from Baseline(Baseline - 1 month - 3 months - 6 months)
- Change in SICF measurements from Baseline(Baseline - 1 month - 3 months - 6 months)
- Change in MMSE scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in phonemic fluencies scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in semantic fluencies scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in digit span forward scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in digit span backward scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in camel and cactus test scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in TMTA scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in TMTB scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in Stroop test scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in Symbol Digit test scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in Block Design test scores from Baseline(Baseline - 2 weeks - 3 months - 6 months)
- Change in The modified EkmanFaces Test from Baseline(Baseline - 2 weeks - 3 months - 6 months)