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

March 1, 2020 updated by: Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
70

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Brescia, Italy, 25123
        • Azienda Ospedaliera Spedali Civili di Brescia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Presymptomatic real tDCS
Asymptomatic subjects - 10 days anodal transcranial direct current stimulation
Device: Anodal transcranial direct current stimulation
10 sessions of anodal transcranial direct current stimulation (5 days/week for 2 weeks)
Sham Comparator: Presymptomatic sham tDCS
Asymptomatic subjects - 10 days sham transcranial direct current stimulation
Device: Sham transcranial direct current stimulation
10 sessions of sham transcranial direct current stimulation (5 days/week for 2 weeks)
Experimental: Symptomatic real tDCS
Symptomatic patients - 10 days anodal transcranial direct current stimulation
Device: Anodal transcranial direct current stimulation
10 sessions of anodal transcranial direct current stimulation (5 days/week for 2 weeks)
Sham Comparator: Symptomatic sham tDCS
Symptomatic patients - 10 days sham transcranial direct current stimulation
Device: Sham transcranial direct current stimulation
10 sessions of sham transcranial direct current stimulation (5 days/week for 2 weeks)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
Baseline - 2 weeks
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).
Baseline - 2 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in SICI measurements from Baseline
Time Frame: Baseline - 1 month - 3 months - 6 months
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
Change in ICF measurements from Baseline
Time Frame: Baseline - 1 month - 3 months - 6 months
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
Change in LICI measurements from Baseline
Time Frame: Baseline - 1 month - 3 months - 6 months
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
Change in SICF measurements from Baseline
Time Frame: Baseline - 1 month - 3 months - 6 months
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
Change in MMSE scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
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
Change in phonemic fluencies scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
Produce as many words as possible beginning with a specified letter in 60 seconds
Baseline - 2 weeks - 3 months - 6 months
Change in semantic fluencies scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
Produce as many words as possible from a category in 60 seconds
Baseline - 2 weeks - 3 months - 6 months
Change in digit span forward scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
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
Change in digit span backward scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
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
Change in camel and cactus test scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
Evaluates associative semantic memory with 64 items presented for naming and word-picture matching.
Baseline - 2 weeks - 3 months - 6 months
Change in TMTA scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
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
Change in TMTB scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
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
Change in Stroop test scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
Measure a person's selective attention capacity and skills, as well as their processing speed ability.
Baseline - 2 weeks - 3 months - 6 months
Change in Symbol Digit test scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
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
Change in Block Design test scores from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
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
Change in The modified EkmanFaces Test from Baseline
Time Frame: Baseline - 2 weeks - 3 months - 6 months
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 31, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 2, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 3, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 1, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NP2441

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All data, including outcome measure results, study protocol and statistical analysis plan, will be shared.

IPD Sharing Time Frame

Data will be shared after the study completion indefinitely.

IPD Sharing Access Criteria

Reasonable request

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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