- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03422250
Non-invasive Stimulation of Brain Networks and Cognition in Alzheimer's Disease and Frontotemporal Dementia (NetCogBs)
A Non-invasive, Multimodal Approach to Restore Functional Networks and Cognition in Alzheimer's Disease and Frontotemporal Dementia
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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-
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Brescia, Italy, 25125
- IRCCS Centro San Giovanni di Dio Fatebenefratelli
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of AD or bvFTD according to current clinical criteria (Albert et al., 2011; Rascovsky et al., 2011)
- Ability to provide written informed consent
- Availability of a collateral source
Exclusion Criteria:
- Moderate/severe dementia
- Presence of any medical or psychiatric illness that could interfere in completing assessments
Exclusion Criteria for MRI and tDCS:
- metal implants, pace-makers, prosthetic heart valves
- claustrophobia
- history of epilepsy
- pregnancy
Exclusion Criteria for controls:
- Current or past history of clinical, neurological, or psychiatric conditions that could interfere with the assessment (e.g., transient ischemic attack, ictus, head trauma, epilepsy, multiple sclerosis, neuropathy, mood disorders, substance abuse)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm 1
Alzheimer's disease (AD): anodal tDCS of the default mode network (DMN)
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10 daily 25-minutes tDCS sessions over two weeks.
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Experimental: Arm 2
Alzheimer's disease (AD): cathodal tDCS of the salience network (SN)
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10 daily 25-minutes tDCS sessions over two weeks.
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Experimental: Arm 3
Behavioral-variant frontotemporal dementia (bvFTD): anodal tDCS of the salience network (SN)
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10 daily 25-minutes tDCS sessions over two weeks.
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Experimental: Arm 4
Behavioral-variant frontotemporal dementia (bvFTD): cathodal tDCS of the default mode network (DMN)
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10 daily 25-minutes tDCS sessions over two weeks.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Clinical Disease Severity (CDR)
Time Frame: Baseline, post tDCS (week 3)
|
CDR - Clinical Dementia Rating score The clinical dementia rating (CDR) is a clinical global rating scale administered to both the participant and the caregiver, assessing 6 domains of participant function: memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care. Each domain is based on a 5-point scale ranging from no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 to severe impairment=3. The global CDR score is computed via a memory-weighted averaging algorithm of the six domain scores and ranges from 0 to 5. The CDR-sum of boxes (CDR-SB) is the sum of the individual domain scores and ranges from 0 to 18. Higher scores indicate more clinical impairment. Negative changes at post tDCS compared to baseline represent an improvement on the scale. |
Baseline, post tDCS (week 3)
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Change in Behavioral Symptom Severity (NPI)
Time Frame: Baseline, post tDCS (week 3)
|
The Neuropsychiatric Inventory (NPI) is a behavioral scale administered to the caregiver assessing 12 dimensions: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, euphoria, apathy, disinhibition, irritability, aberrant motor activity, nighttime behaviors, and appetite/eating.
Each dimension has multiple screening questions relating to symptoms.
If the answer to the screening questions is "Yes", the dimensional-score is the product of frequency (1=occasionally to 4=very frequently) and severity (1=Mild to 3=Severe) of symptoms.
Dimensional-scores are summed (from 0 to 144).
Higher scores indicate greater behavioral disturbances.
Negative changes at post tDCS compared to baseline represent an improvement on the scale.
|
Baseline, post tDCS (week 3)
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Change in Behavioral Symptom Severity (FBI)
Time Frame: Baseline, post tDCS (week 3)
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The Frontal Behavioral Inventory (FBI) is a 24-item inventory designed to assess behavior and personality changes via caregiver.
Item-level scores range from 0=none, 1=mild/occasional, 2=moderate, 3=severe/most of the time.
Item-scores are summed (from 0 to 72).
Higher scores indicate greater behavioral/personality disturbances.
Negative changes at post tDCS compared to baseline represent an improvement on the scale.
|
Baseline, post tDCS (week 3)
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Change in Functional Connectivity
Time Frame: Baseline, post tDCS (week 3)
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Default mode network (DMN) and salience network (SN) mean functional connectivity is assessed on resting state functional MRI.
Functional connectivity is standardized to Z scores and thresholded at Z>2. Higher values denote greater functional connectivity.
A positive change at post tDCS compared to baseline represents an increase in resting-state functional connectivity.
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Baseline, post tDCS (week 3)
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Change in Cerebral Blood Flow
Time Frame: Baseline, post tDCS (week 3)
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Default mode network (DMN) and salience network (SN) mean cerebral blood flow is assessed on arterial spin labeling.
Cerebral blood flow is computed by averaging values across the DMN and SN regions of interest.
Cerebral blood flow is a measure of brain perfusion, higher values denoting higher perfusion.
A positive change at post tDCS compared to baseline represents an increase in perfusion.
|
Baseline, post tDCS (week 3)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Cognition: Memory
Time Frame: Baseline, post tDCS (week 3)
|
The composite memory score consists of the averaged Z-standardized scores of 5 memory tests: immediate and delayed auditory verbal learning test recall, Rey-Osterrieth complex figure recall, story recall, digit span backward and forward tests.
Each test score is normalized to an independent dataset of healthy controls.
Z-scores have no minimum/maximum values.
A z-score of 0 is equal to the mean and is considered normal.
Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Higher values denote better memory performance.
Positive changes at post tDCS compared to baseline represent an improvement in memory.
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Baseline, post tDCS (week 3)
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Change in Cognition: Language
Time Frame: Baseline, post tDCS (week 3)
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The composite language score consists of the averaged Z-standardized scores of 2 language tests: verbal fluency and token tests.
Each test score is normalized to an independent dataset of healthy controls.
Z-scores have no minimum/maximum values.
A z-score of 0 is equal to the mean and is considered normal.
Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Higher values denote better language performance.
Positive changes at post tDCS compared to baseline represent an improvement in language.
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Baseline, post tDCS (week 3)
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Change in Cognition: Executive Function
Time Frame: Baseline, post tDCS (week 3)
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The composite executive function score consists of the averaged Z-standardized scores of 2 executive functions tests: trail making test part A and part B tests.
Each test score is normalized to an independent dataset of healthy controls and inverted.
Z-scores have no minimum/maximum values.
A z-score of 0 is equal to the mean and is considered normal.
Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Higher values denote better executive function performance.
Positive changes at post tDCS compared to baseline represent an improvement in executive functions.
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Baseline, post tDCS (week 3)
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Change in Cognition: Visuospatial Function
Time Frame: Baseline, post tDCS (week 3)
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The visuospatial function score consists of the Z-standardized scores for the Rey-Osterrieth complex figure copy test.
Scores are normalized to an independent dataset of healthy controls.
Z-scores have no minimum/maximum values.
A z-score of 0 is equal to the mean and is considered normal.
Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Higher values denote better visuospatial performance.
Positive changes at post tDCS compared to baseline represent an improvement in visuospatial functions.
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Baseline, post tDCS (week 3)
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Change in Cognition: Emotion Recognition
Time Frame: Baseline, post tDCS (week 3)
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The composite emotion recognition score consists of the averaged Z-standardized scores for 2 emotion recognition tests: reading the Mind in the Eyes and 60 Ekman faces tests.
Each test score is normalized to an independent dataset of healthy controls.
Z-scores have no minimum/maximum values.
A z-score of 0 is equal to the mean and is considered normal.
Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Higher values denote better emotion recognition performance.
Positive changes at post tDCS compared to baseline represent an improvement in emotion recognition.
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Baseline, post tDCS (week 3)
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Change in Structural Connectivity: FA
Time Frame: Baseline, post tDCS (week 3)
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Fractional anisotropy (FA) is assessed on diffusion weighted imaging.
FA values are averaged in default mode network (DMN) and salience network (SN) regions of interest.
FA values denote the directionality of water diffusivity, ranging from 0 (isotropic diffusion) to 1 (anisotropic diffusion).
Higher values denote higher directionality and connectivity.
Positive changes at post tDCS compared to baseline represent an improvement in the measure.
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Baseline, post tDCS (week 3)
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Change in Structural Connectivity: MD, AxD, RaD
Time Frame: Baseline, post tDCS (week 3)
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Mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RaD) are assessed on diffusion weighted imaging.
MD, AxD, RaD values are averaged in default mode network (DMN) and salience network (SN) regions of interest.
MD, AxD, and RaD measure water diffusion and are expressed in mm^2/s (starting from 0 with no maximum value; scaled at x10^-3).
Higher values denote higher diffusion and lower connectivity.
Negative changes at post tDCS compared to baseline represent an improvement in the measure.
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Baseline, post tDCS (week 3)
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Collaborators and Investigators
Investigators
- Principal Investigator: Michela Pievani, PhD, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
Publications and helpful links
General Publications
- Pievani M, Pini L, Cappa SF, Frisoni GB. Brain networks stimulation in dementia: insights from functional imaging. Curr Opin Neurol. 2016 Dec;29(6):756-762. doi: 10.1097/WCO.0000000000000387.
- Pini L, Pizzini FB, Boscolo-Galazzo I, Ferrari C, Galluzzi S, Cotelli M, Gobbi E, Cattaneo A, Cotelli MS, Geroldi C, Zanetti O, Corbetta M, van den Heuvel M, Frisoni GB, Manenti R, Pievani M. Brain network modulation in Alzheimer's and frontotemporal dementia with transcranial electrical stimulation. Neurobiol Aging. 2022 Mar;111:24-34. doi: 10.1016/j.neurobiolaging.2021.11.005. Epub 2021 Nov 20.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Metabolic Diseases
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Neurocognitive Disorders
- Neurodegenerative Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Tauopathies
- Language Disorders
- Communication Disorders
- Speech Disorders
- Frontotemporal Lobar Degeneration
- Aphasia
- Dementia
- Alzheimer Disease
- Frontotemporal Dementia
- Aphasia, Primary Progressive
- Pick Disease of the Brain
Other Study ID Numbers
- GR-2011-02349787
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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