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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02999282
Recruitment Status : Completed
First Posted : December 21, 2016
Last Update Posted : March 3, 2020
Sponsor:
Information provided by (Responsible Party):
Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

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.

Condition or disease Intervention/treatment Phase
Frontotemporal Dementia GRN Related Frontotemporal Dementia Device: Anodal transcranial direct current stimulation Device: Sham transcranial direct current stimulation Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Rehabilitative Trial for the Recovery of Neurophysiological Parameters in Progranulin Mutation Carriers Through the Use of Transcranial Direct Current Stimulation (tDCS)
Actual Study Start Date : October 31, 2016
Actual Primary Completion Date : June 30, 2019
Actual Study Completion Date : June 30, 2019


Arm Intervention/treatment
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)




Primary Outcome Measures :
  1. 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)

  2. 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 Outcome Measures :
  1. 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)

  2. 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).

  3. 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).

  4. 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).

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02999282


Locations
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Italy
Azienda Ospedaliera Spedali Civili di Brescia
Brescia, Italy, 25123
Sponsors and Collaborators
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Investigators
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Principal Investigator: Barbara Borroni, MD Azienda Ospedaliera Spedali Civili, Brescia
Principal Investigator: Alberto Benussi, MD Università degli Studi di Brescia
Publications:
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Responsible Party: Barbara Borroni, Associated Professor; MD, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
ClinicalTrials.gov Identifier: NCT02999282    
Other Study ID Numbers: NP2441
First Posted: December 21, 2016    Key Record Dates
Last Update Posted: March 3, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All data, including outcome measure results, study protocol and statistical analysis plan, will be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Data will be shared after the study completion indefinitely.
Access Criteria: Reasonable request
Keywords provided by Barbara Borroni, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia:
TMS
tDCS
Rehabilitation
Additional relevant MeSH terms:
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Dementia
Frontotemporal Dementia
Aphasia, Primary Progressive
Pick Disease of the Brain
Frontotemporal Lobar Degeneration
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Neurodegenerative Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations