Neurodegenerative DiseaseNCT07567664
Tracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases
A study testing 3 Tesla MRI without contrast medium, Blood sample for genetic analysis and Cerebrospinal fluid sampling (CSF) in people with Neurodegenerative Disease and Behavioral Variant Frontotemporal Dementia (bvFTD), run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
Neurodegenerative diseases, including frontotemporal lobar degeneration (FTLD) spectrum syndromes, are characterized by the accumulation of insoluble protein aggregates in the central nervous system. Read more about this study
- Who is it for?
- Ages 20 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Neurodegenerative Disease, Behavioral Variant Frontotemporal Dementia (bvFTD), Primary Progressive Aphasia(PPA)
- What is being tested?
- 3 Tesla MRI without contrast medium, Blood sample for genetic analysis and Cerebrospinal fluid sampling (CSF)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 645 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jun 2017to 1 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult participants, under 85 years of age, diagnosed with bvFTD, semantic variant PPA, non-fluent variant PPA, PSP, CBS, and early-stage ALS, according to the criteria of Rascovsky (2011), Gorno-Tempini (2011), Litvan (1996), Armstrong (2013), and Brooks (2000), respectively;
- Participants with genetic forms of FTLD associated with mutations in the c9orf72, GRN, MAPT genes, and asymptomatic family members related to FTLD patients carrying such mutations
- Healthy participants (age between 20 and 30 years old); Healthy participants matched to patients for age and sex
Who cannot join
- Participants with a history of other neurological and/or psychiatric disorders, head trauma, alcohol or psychoactive substance use, or a family history of other neurodegenerative diseases.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Tracking and Predicting Neurodegeneration Spreading Across the Brain Connectome
Neurodegenerative diseases, including frontotemporal lobar degeneration (FTLD) spectrum syndromes, are characterized by the accumulation of insoluble protein aggregates in the central nervous system. A common feature of these diseases is that pathological changes accumulate over time following a stereotyped spatial pattern, which contributes to the onset and progression of clinical symptoms. Until recently, the causes of such progression were still unknown. Recent pathological and neuroimaging studies have, however, suggested that insoluble and pathological protein aggregates are able to alter the conformation of neighboring proteins and spread through cell-to-cell transmission. According to this theory, called the 'brain connectome,' the brain network is established as a set of nodes, which correspond to different anatomical regions.
These brain networks are highly connected to each other and their internal organization is fundamental for an efficient integration of information coming from different regions and to guarantee adequate levels of motor/cognitive performance. Thanks to magnetic resonance studies and research in the field of brain networks, it is possible to understand the pathophysiology of neurodegenerative diseases and reveal the connectivity profiles associated with different clinical outcomes.
Read more
The main objective of this project is to explore the mechanisms of neurodegeneration associated with the different FTLD spectrum syndromes, and in particular the hypothesis that the neurodegenerative process is driven by the structural architecture of the brain 'connectome'. The ultimate goal is to apply mathematical models to structural and functional connectivity data to predict the evolution of the neurodegenerative process in sporadic and genetic forms of Frontotemporal Lobar Degeneration Disease.
This study aims to investigate the spatiotemporal progression of neurodegeneration in frontotemporal lobar degeneration (FTLD) using advanced neuroimaging and connectomics. 360 patients with sporadic FTLD (including bvFTD, semantic and nonfluent PPA, PSPs, CBS, and ALS) and 65 patients with genetic FTLD (MAPT, GRN, and C9orf72 mutati will be enrolled. The study also plans to enroll 120 subjects who are members of families carrying FLTD-associated mutations (including 60 mutation carriers). Finally, 100 healthy controls will also be enrolled, including 50 young healthy controls and 50 healthy controls comparable with patients by sex and age. Participants will undergo clinical, neuropsychological, and behavioral assessments, blood and Cerebrospinal fluid (CSF) collection, and multimodal 3Tesla Magnetic Resonance Imaging MRI at baseline and every 6 months for up to 2 years. Primary objectives include mapping longitudinal changes in structural and functional brain networks, developing predictive models of network degeneration and clinical decline, and characterizing protein-specific patterns of network degeneration. Secondary aims include identifying early network biomarkers in presymptomatic carriers and correlating network changes with biological markers.
- Conditions
- Neurodegenerative Disease, Behavioral Variant Frontotemporal Dementia (bvFTD), Primary Progressive Aphasia(PPA), Progressive Supranuclear Palsy(PSP), Amyotrophic Lateral Sclerosis (ALS), Cortical Basal Syndrome (CBS)
- Being tested
- 3 Tesla MRI without contrast medium, Blood sample for genetic analysis, Cerebrospinal fluid sampling (CSF), Neurological evaluation, Neuropsychological evaluation
- Medical subject headings
- Neurodegenerative Diseases, Aphasia, Primary Progressive, Supranuclear Palsy, Progressive, Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
3 Tesla MRI without contrast mediumDiagnostic test
3 Tesla MRI examination without contrast medium in which resting functional MRI sequences, diffusion-weighted sequence, structural MRI sequences will be obtained
Blood sample for genetic analysisGenetic
During the screening/basal visit, a blood sample will be taken to assess the genetic profile of patients, consanguineous family members, and healthy elderly controls. Objective is to evaluate the major genes that have been shown to play a role in the pathogenesis of FTLD The genes GRN, MAPT, C9orf72, TARDBP, SOD1, FUS, OPTN, VCP will be analyzed.
Cerebrospinal fluid sampling (CSF)Diagnostic test
During the baseline visit, patients will undergo lumbar puncture for the collection of CSF for quantification of biological biomarkers
Neurological evaluationDiagnostic test
A neurological evaluation will be conducted in order to be able to exclude from the study all participants with a history of psychiatric illness, head injury, alcohol or psychotropic substance use
Neuropsychological evaluationDiagnostic test
A neuropsychological assessment will be conducted in order to be able to exclude from the study all participants with a history of psychiatric illness, alcohol or psychotropic substance use
| Study group | Role | What they receive |
|---|---|---|
| Participants with the spectrum of FTLD, asymptomatic familiar, healthy elderly and young controls | Experimental | Partecipants affected by behavioral variant of FTLD (bvFTD), primary progressive aphasia (PPA), semantic variant of PPA (svPPA), non-fluent variant of PPA (nfvPPA), progressive supranuclear paralysis (PSP), corticobasal syndrome (CBS), amyotrophic lateral sclerosis (ALS), genetic and sporadic FTLD. Asymptomatic familiar. Healthy elderly and young controls. Receives: Diagnostic Test: 3 Tesla MRI without contrast medium; Genetic: Blood sample for genetic analysis; Diagnostic Test: Cerebrospinal fluid sampling (CSF); Diagnostic Test: Neurological evaluation; Diagnostic Test: Neuropsychological evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Longitudinal change in the structural connectome via Neurite Orientation Dispersion and Density Imaging (NODDI)
Evaluating structural white matter integrity over time through graph-theoretical analysis based on NODDI-derived metrics
Measured: 6 months, 12 months, 18 months, 24 months
Longitudinal change in the structural connectome via Diffusion Tensor Imaging (DTI)
Evaluating structural white matter integrity over time through graph-theoretical analysis
Measured: 6 months, 12 months, 18 months, 24 months
Longitudinal change in brain functional connectome via functional MRI
Evaluating functional brain changes in functional brain networks using graph-theoretical analysis of fMRI-derived connectivity
Measured: 6 months, 12 months, 18 months, 24 months
Prediction of pathological spreading through the structural connectome
To predict spatial and temporal spreading of neurodegeneration through the structural connectome using network diffusion model
Measured: 6 months, 12 months, 18 months, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2026
- Study start1 Jun 2017
- Primary completion15 Feb 2027 (estimated)
- Study completion1 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neurodegenerative DiseaseStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Intervention, multicentric and multiparametric study
- Masking
- None (open label)
- Enrolment
- 645 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Collaborators
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Azienda Ospedaliera San Gerardo di Monza, Istituto Auxologico Italiano
- Responsible party
- Principal investigator, Prof. Massimo Filippi, IRCCS San Raffaele
- Investigators
- Prof. Massimo Filippi, Study director, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07567664
- Sponsor's protocol ID
- StG-2016_714388_NeuroTRACK_
- Status last verified
- Apr 2026
- First submitted
- 26 Nov 2025
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Still undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tracking and Predicting Neurodegeneration Spreading Across the Brain Connectome
- ClinicalTrials.gov ID
- NCT07567664
- Acronym / sponsor ID
- StG-2016_714388_NeuroTRACK_
- Conditions
- Neurodegenerative Disease, Behavioral Variant Frontotemporal Dementia (bvFTD), Primary Progressive Aphasia(PPA), Progressive Supranuclear Palsy(PSP), Amyotrophic Lateral Sclerosis (ALS), Cortical Basal Syndrome (CBS)
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 645 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Collaborators
- IRCCS Istituto delle Scienze Neurologiche di Bologna, Azienda Ospedaliera San Gerardo di Monza, Istituto Auxologico Italiano
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 15 Feb 2027 (estimated)
- Study completion
- 1 Mar 2027 (estimated)
- First posted
- 5 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neurodegenerative diseases, including frontotemporal lobar degeneration (FTLD) spectrum syndromes, are characterized by the accumulation of insoluble protein aggregates in the central nervous system. A common feature of these diseases is that pathological changes accumulate over time following a stereotyped spatial pattern, which contributes to the onset and progression of clinical symptoms. Until recently, the causes of such progression were still unknown. Recent pathological and neuroimaging studies have, however, suggested that insoluble and pathological protein aggregates are able to alter the conformation of neighboring proteins and spread through cell-to-cell transmission. According to this theory, called the 'brain connectome,' the brain network is established as a set of nodes, which correspond to different anatomical regions.
These brain networks are highly connected to each other and their internal organization is fundamental for an efficient integration of information coming from different regions and to guarantee adequate levels of motor/cognitive performance. Thanks to magnetic resonance studies and research in the field of brain networks, it is possible to understand the pathophysiology of neurodegenerative diseases and reveal the connectivity profiles associated with different clinical outcomes.
The main objective of this project is to explore the mechanisms of neurodegeneration associated with the different FTLD spectrum syndromes, and in particular the hypothesis that the neurodegenerative process is driven by the structural architecture of the brain 'connectome'. The ultimate goal is to apply mathematical models to structural and functional connectivity data to predict the evolution of the neurodegenerative process in sporadic and genetic forms of Frontotemporal Lobar Degeneration Disease.
This study aims to investigate the spatiotemporal progression of neurodegeneration in frontotemporal lobar degeneration (FTLD) using advanced neuroimaging and connectomics. 360 patients with sporadic FTLD (including bvFTD, semantic and nonfluent PPA, PSPs, CBS, and ALS) and 65 patients with genetic FTLD (MAPT, GRN, and C9orf72 mutati will be enrolled. The study also plans to enroll 120 subjects who are members of families carrying FLTD-associated mutations (including 60 mutation carriers). Finally, 100 healthy controls will also be enrolled, including 50 young healthy controls and 50 healthy controls comparable with patients by sex and age. Participants will undergo clinical, neuropsychological, and behavioral assessments, blood and Cerebrospinal fluid (CSF) collection, and multimodal 3Tesla Magnetic Resonance Imaging MRI at baseline and every 6 months for up to 2 years. Primary objectives include mapping longitudinal changes in structural and functional brain networks, developing predictive models of network degeneration and clinical decline, and characterizing protein-specific patterns of network degeneration. Secondary aims include identifying early network biomarkers in presymptomatic carriers and correlating network changes with biological markers.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Intervention, multicentric and multiparametric study
| Arm | Type | Receives |
|---|---|---|
| Participants with the spectrum of FTLD, asymptomatic familiar, healthy elderly and young controls | Experimental | Diagnostic Test: 3 Tesla MRI without contrast medium, Genetic: Blood sample for genetic analysis, Diagnostic Test: Cerebrospinal fluid sampling (CSF), Diagnostic Test: Neurological evaluation, Diagnostic Test: Neuropsychological evaluationPartecipants affected by behavioral variant of FTLD (bvFTD), primary progressive aphasia (PPA), semantic variant of PPA (svPPA), non-fluent variant of PPA (nfvPPA), progressive supranuclear paralysis (PSP), corticobasal syndrome (CBS), amyotrophic lateral sclerosis (ALS), genetic and sporadic FTLD. Asymptomatic familiar. Healthy elderly and young controls. |
Who may qualify
- Ages
- 20 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult participants, under 85 years of age, diagnosed with bvFTD, semantic variant PPA, non-fluent variant PPA, PSP, CBS, and early-stage ALS, according to the criteria of Rascovsky (2011), Gorno-Tempini (2011), Litvan (1996), Armstrong (2013), and Brooks (2000), respectively;
- Participants with genetic forms of FTLD associated with mutations in the c9orf72, GRN, MAPT genes, and asymptomatic family members related to FTLD patients carrying such mutations
- Healthy participants (age between 20 and 30 years old); Healthy participants matched to patients for age and sex
Key exclusion criteria (1 listed)
- Participants with a history of other neurological and/or psychiatric disorders, head trauma, alcohol or psychoactive substance use, or a family history of other neurodegenerative diseases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 3 Tesla MRI without contrast medium3 Tesla MRI examination without contrast medium in which resting functional MRI sequences, diffusion-weighted sequence, structural MRI sequences will be obtained | Diagnostic test | Participants with the spectrum of FTLD, asymptomatic familiar, healthy elderly and young controls |
| Blood sample for genetic analysisDuring the screening/basal visit, a blood sample will be taken to assess the genetic profile of patients, consanguineous family members, and healthy elderly controls. Objective is to evaluate the major genes that have been shown to play a role in the pathogenesis of FTLD The genes GRN, MAPT, C9orf72, TARDBP, SOD1, FUS, OPTN, VCP will be analyzed. | Genetic | Participants with the spectrum of FTLD, asymptomatic familiar, healthy elderly and young controls |
| Cerebrospinal fluid sampling (CSF)During the baseline visit, patients will undergo lumbar puncture for the collection of CSF for quantification of biological biomarkers | Diagnostic test | Participants with the spectrum of FTLD, asymptomatic familiar, healthy elderly and young controls |
| Neurological evaluationA neurological evaluation will be conducted in order to be able to exclude from the study all participants with a history of psychiatric illness, head injury, alcohol or psychotropic substance use | Diagnostic test | Participants with the spectrum of FTLD, asymptomatic familiar, healthy elderly and young controls |
| Neuropsychological evaluationA neuropsychological assessment will be conducted in order to be able to exclude from the study all participants with a history of psychiatric illness, alcohol or psychotropic substance use | Diagnostic test | Participants with the spectrum of FTLD, asymptomatic familiar, healthy elderly and young controls |
Primary outcome
Longitudinal change in the structural connectome via Neurite Orientation Dispersion and Density Imaging (NODDI)
Time frame: 6 months, 12 months, 18 months, 24 months
Evaluating structural white matter integrity over time through graph-theoretical analysis based on NODDI-derived metrics
Longitudinal change in the structural connectome via Diffusion Tensor Imaging (DTI)
Time frame: 6 months, 12 months, 18 months, 24 months
Evaluating structural white matter integrity over time through graph-theoretical analysis
Longitudinal change in brain functional connectome via functional MRI
Time frame: 6 months, 12 months, 18 months, 24 months
Evaluating functional brain changes in functional brain networks using graph-theoretical analysis of fMRI-derived connectivity
Prediction of pathological spreading through the structural connectome
Time frame: 6 months, 12 months, 18 months, 24 months
To predict spatial and temporal spreading of neurodegeneration through the structural connectome using network diffusion model
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Individual participant dataSharing planned: Undecided. Still undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Prof. Massimo Filippi study director
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 3 Tesla MRI without contrast medium, Blood sample for genetic analysis and Cerebrospinal fluid sampling (CSF) in people with Neurodegenerative Disease and Behavioral Variant Frontotemporal Dementia (bvFTD), run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Longitudinal change in the structural connectome via Neurite Orientation Dispersion and Density Imaging (NODDI) (time frame: 6 months, 12 months, 18 months, 24 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2026.