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

NCT ID: NCT02999282

Last Updated: 2020-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2019-06-30

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.

Conditions

Frontotemporal Dementia; GRN Related Frontotemporal Dementia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Presymptomatic real tDCS

Asymptomatic subjects - 10 days anodal transcranial direct current stimulation

Group Type: EXPERIMENTAL

Anodal transcranial direct current stimulation

Intervention Type: DEVICE

10 sessions of anodal transcranial direct current stimulation (5 days/week for 2 weeks)

Presymptomatic sham tDCS

Asymptomatic subjects - 10 days sham transcranial direct current stimulation

Group Type: SHAM_COMPARATOR

Sham transcranial direct current stimulation

Intervention Type: DEVICE

10 sessions of sham transcranial direct current stimulation (5 days/week for 2 weeks)

Symptomatic real tDCS

Symptomatic patients - 10 days anodal transcranial direct current stimulation

Group Type: EXPERIMENTAL

Anodal transcranial direct current stimulation

Intervention Type: DEVICE

10 sessions of anodal transcranial direct current stimulation (5 days/week for 2 weeks)

Symptomatic sham tDCS

Symptomatic patients - 10 days sham transcranial direct current stimulation

Group Type: SHAM_COMPARATOR

Sham transcranial direct current stimulation

Intervention Type: DEVICE

10 sessions of sham transcranial direct current stimulation (5 days/week for 2 weeks)

Interventions

Anodal transcranial direct current stimulation

10 sessions of anodal transcranial direct current stimulation (5 days/week for 2 weeks)

Intervention Type: DEVICE

Sham transcranial direct current stimulation

10 sessions of sham transcranial direct current stimulation (5 days/week for 2 weeks)

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

OTHER

Sponsor Role: lead

Responsible Party

Barbara Borroni

Associated Professor; MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Barbara Borroni, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Spedali Civili, Brescia

Alberto Benussi, MD

Role: PRINCIPAL_INVESTIGATOR

Università degli Studi di Brescia

Locations

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, , Italy

Countries

Italy

References

Benussi A, Cosseddu M, Filareto I, Dell'Era V, Archetti S, Sofia Cotelli M, Micheli A, Padovani A, Borroni B. Impaired long-term potentiation-like cortical plasticity in presymptomatic genetic frontotemporal dementia. Ann Neurol. 2016 Sep;80(3):472-6. doi: 10.1002/ana.24731. Epub 2016 Aug 10.

Reference Type: BACKGROUND

PMID: 27438089 (View on PubMed)

Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, Mourdoukoutas AP, Kronberg G, Truong D, Boggio P, Brunoni AR, Charvet L, Fregni F, Fritsch B, Gillick B, Hamilton RH, Hampstead BM, Jankord R, Kirton A, Knotkova H, Liebetanz D, Liu A, Loo C, Nitsche MA, Reis J, Richardson JD, Rotenberg A, Turkeltaub PE, Woods AJ. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016 Sep-Oct;9(5):641-661. doi: 10.1016/j.brs.2016.06.004. Epub 2016 Jun 15.

Reference Type: BACKGROUND

PMID: 27372845 (View on PubMed)

Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.

Reference Type: BACKGROUND

PMID: 25797650 (View on PubMed)

Other Identifiers

NP2441

Identifier Type: -

Identifier Source: org_study_id