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

Frontotemporal Dementia Clinical Trial

— ReRescuePGR  

Official title:

Rehabilitative Trial for the Recovery of Neurophysiological Parameters in Progranulin Mutation Carriers Through the Use of Transcranial Direct Current Stimulation (tDCS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02999282
• Other study ID #: NP2441
• Status: Completed
• Phase: N/A
• Start date: October 31, 2016
• Est. completion date: June 30, 2019

Study information

• Verified date: March 2020
• Source: Azienda Ospedaliera Spedali Civili di Brescia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: June 30, 2019
• Est. primary completion date: June 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Aphasia, Primary Progressive
• Dementia
• Frontotemporal Dementia
• Frontotemporal Lobar Degeneration
• GRN Related Frontotemporal Dementia
• Pick Disease of the Brain

Intervention

Device:
• Anodal transcranial direct current stimulation
10 sessions of anodal transcranial direct current stimulation (5 days/week for 2 weeks)
• Sham transcranial direct current stimulation
10 sessions of sham transcranial direct current stimulation (5 days/week for 2 weeks)

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera Spedali Civili di Brescia	Brescia

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Ospedaliera Spedali Civili di Brescia

Country where clinical trial is conducted

Italy, 

References & 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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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 - 1 month - 3 months - 6 months
Secondary	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 - 1 month - 3 months - 6 months
Secondary	Change in LICI measurements from Baseline	By using transcranial magnetic stimulation (TMS), the investigators will evaluate the effects of frontal and prefrontal anodal transcranial magnetic stimulation on long interval intracortical inhibition (LICI).	Baseline - 1 month - 3 months - 6 months
Secondary	Change in SICF 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 facilitation (SICF).	Baseline - 1 month - 3 months - 6 months
Secondary	Change in MMSE scores from Baseline	The Mini Mental State Examination (MMMSE) is a 30-point questionnaire that is used to measure cognitive impairment.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in phonemic fluencies scores from Baseline	Produce as many words as possible beginning with a specified letter in 60 seconds	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in semantic fluencies scores from Baseline	Produce as many words as possible from a category in 60 seconds	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in digit span forward scores from Baseline	Participants hear a sequence of numerical digits and are tasked to recall the sequence correctly, with increasingly longer sequences being tested in each trial. The participant's span is the longest number of sequential digits that can accurately be remembered.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in digit span backward scores from Baseline	Participants hear a sequence of numerical digits and are tasked to recall the sequence correctly in reverse order, with increasingly longer sequences being tested in each trial. The participant's span is the longest number of sequential digits that can accurately be remembered.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in camel and cactus test scores from Baseline	Evaluates associative semantic memory with 64 items presented for naming and word-picture matching.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in TMTA scores from Baseline	The task requires a subject to connect a sequence of 25 consecutive targets on a sheet of paper to examine cognitive processing speed.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in TMTB scores from Baseline	The task requires a subject to connect a sequence of 25 consecutive targets on a sheet of paper, alternating between numbers and letters, to examine executive functioning.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in Stroop test scores from Baseline	Measure a person's selective attention capacity and skills, as well as their processing speed ability.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in Symbol Digit test scores from Baseline	It consists of digit-symbol pairs followed by a list of digits. Under each digit the subject should write down the corresponding symbol as fast as possible. The number of correct symbols within the allowed time is measured.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in Block Design test scores from Baseline	To evaluated spatial visualization ability and motor skills. The test-taker uses hand movements to rearrange blocks that have various color patterns on different sides to match a pattern. The items in a block design test are scored both by accuracy in matching the pattern and by speed in completing each item.	Baseline - 2 weeks - 3 months - 6 months
Secondary	Change in The modified EkmanFaces Test from Baseline	Each face is presented on a sheet with six labels of basic emotions below the photograph. The patient was required to respond verbally, deciding the label that best described the facial expression shown.	Baseline - 2 weeks - 3 months - 6 months