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

NCT02999282 | Completed DMC

• 1 other identifier: NP2441
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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.

Conditions

Frontotemporal Dementia; GRN Related Frontotemporal Dementia

Keywords

TMS; tDCS; Rehabilitation

Outcome Measures

Primary Outcomes (2)

• Change in SICI measurements from Baseline

  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)

  Baseline - 2 weeks

• Change in ICF measurements from Baseline

  By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of frontal and prefrontal anodal transcranial magnetic stimulation on intracortical facilitation (ICF).

  Baseline - 2 weeks

Secondary Outcomes (16)

• 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

Study Arms (4)

Presymptomatic real tDCS

EXPERIMENTAL

Asymptomatic subjects - 10 days anodal transcranial direct current stimulation

Device: Anodal transcranial direct current stimulation

Presymptomatic sham tDCS

SHAM COMPARATOR

Asymptomatic subjects - 10 days sham transcranial direct current stimulation

Device: Sham transcranial direct current stimulation

Symptomatic real tDCS

EXPERIMENTAL

Symptomatic patients - 10 days anodal transcranial direct current stimulation

Device: Anodal transcranial direct current stimulation

Symptomatic sham tDCS

SHAM COMPARATOR

Symptomatic patients - 10 days sham transcranial direct current stimulation

Device: Sham transcranial direct current stimulation

Interventions

Anodal transcranial direct current stimulation DEVICE

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

Presymptomatic real tDCS; Symptomatic real tDCS

Sham transcranial direct current stimulation DEVICE

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

Presymptomatic sham tDCS; Symptomatic sham tDCS

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: lead

Study Sites (1)

Azienda Ospedaliera Spedali Civili di Brescia

Brescia, 25123, Italy

Location

Related Publications (3)

• 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.

  PMID: 27438089 BACKGROUND

• 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.

  PMID: 27372845 BACKGROUND

• 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.

  PMID: 25797650 BACKGROUND

MeSH Terms

Conditions

Frontotemporal Dementia

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Barbara Borroni, MD

  Azienda Ospedaliera Spedali Civili, Brescia

  PRINCIPAL INVESTIGATOR

• Alberto Benussi, MD

  Università degli Studi di Brescia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associated Professor; MD

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 21, 2016
• Study Start: October 31, 2016
• Primary Completion: June 30, 2019
• Study Completion: June 30, 2019
• Last Updated: March 3, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the study completion indefinitely.
• Access Criteria: Reasonable request

Locations

IT (1)