Clinical trial NCT03422250: Non-invasive Stimulation of Brain Networks and Cognition in Alzheimer's Disease and Frontotemporal Dementia
Official title: A Non-invasive, Multimodal Approach to Restore Functional Networks and Cognition in Alzheimer's Disease and Frontotemporal Dementia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Alzheimer's Disease
Frontotemporal Dementia, Behavioral Variant
Lead sponsor: IRCCS Centro San Giovanni di Dio Fatebenefratelli
Sponsor class: OTHER
First posted: 2018-02-05
Enrollment: 45
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This pilot study aims to test clinical and connectivity changes following non-invasive stimulation of disease-specific networks in Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD). Brain network stimulation will be carried out with transcranial direct current stimulation (tDCS). Target networks will be the default mode network (DMN) and salience network (SN). Twenty AD and 20 bvFTD patients will be recruited and assessed with a comprehensive clinical, behavioral and cognitive battery, and 3 Tesla MRI scan (including resting-state functional MRI, arterial spin labeling, diffusion tensor imaging, structural MRI) at three time-points: baseline, after tDCS, and after 6 months. Patients will be randomized to 2 arms: anodal stimulation of the disease-specific network (DMN in AD, SN in bvFTD) or cathodal stimulation of the anti-correlated network (SN in AD, DMN in bvFTD). The intervention will consist of 10 tDCS sessions over two weeks. Cerebrospinal fluid (CSF) samples will be collected at baseline for biomarker's assessment; blood samples will be collected at each time-point to assess changes in peripheral inflammatory markers. Blood and CSF collection will be optional. A sample of 20 elderly controls will be included for baseline comparisons.


Eligibility criteria: 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)

Primary outcomes:
measure: Change in Clinical Disease Severity (CDR)
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Behavioral Symptom Severity (NPI)
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Behavioral Symptom Severity (FBI)
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Functional Connectivity
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Cerebral Blood Flow
timeFrame: Baseline, post tDCS (week 3)
Secondary outcomes:
measure: Change in Cognition: Memory
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Cognition: Language
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Cognition: Executive Function
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Cognition: Visuospatial Function
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Cognition: Emotion Recognition
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Structural Connectivity: FA
timeFrame: Baseline, post tDCS (week 3)
measure: Change in Structural Connectivity: MD, AxD, RaD
timeFrame: Baseline, post tDCS (week 3)
Other outcomes:
Locations:
city: Brescia
country: Italy
facility: IRCCS Centro San Giovanni di Dio Fatebenefratelli
Study officials:
affiliation: IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
name: Michela Pievani, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.