Neuroinflammation in FTLD

Leiden University Medical Center (LUMC)

Status

Active, not recruiting

Conditions

Progressive Supranuclear Palsy(PSP)

Frontotemporal Lobar Degeneration (FTLD)

Corticobasal Syndrome(CBS)

Primary Progressive Aphasia(PPA)

Behavioral Variant Frontotemporal Dementia (bvFTD)

Treatments

Diagnostic Test: Neuropsychological assessment

Diagnostic Test: 7T MRI scan

Diagnostic Test: Blood withdrawal

Diagnostic Test: Clinical measures

Diagnostic Test: CSF

Study type

Observational

Funder types

Other

Identifiers

NCT06870838

P21.090

Details and patient eligibility

About

The goal of this observational study is to investigate the role of neuroinflammation in frontotemporal lobar degeneration (FTLD). The main aims of this study are:

To elucidate the role and timing of neuroinflammation in FTLD by using a combination of clinical measures, 7T MRI, and CSF biomarkers;
To differentiate FTLD-TDP and FTLD-tau during life using biomarkers for neuroinflammation;
To identify biomarkers to predict and monitor disease progression in FTLD;

Secondary aim:

1. To explore the role of brain clearance in the disease process of FTLD.

Participants will undergo 7T MRI scans, blood and CSF collection, clinical, neurological, and neuropsychological evaluation.

Full description

At baseline, the study will involve the following procedures: clinical assessment including neurological and neuropsychological investigation, blood sampling, and a voluntarily lumbar puncture on the first day at the Erasmus MC University Medical Center, (EMC) and two sessions of 7T MRI scanning on the second day at the Leiden University Medical Center (LUMC). After one year, clinical assessment and blood analyses will be repeated in the EMC to assess disease progression. The aim is to include 25 patients with probable or definite FTLD-tau, 25 patients with probable or definite FTLD-TDP, 50 healthy individuals with 50% risk to carry a mutation in MAPT or GRN, or the C9orf72 HRE. If necessary for age matching, 10 additional healthy subjects without increased risk of FTLD will be included.

Enrollment

110 estimated patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Ability to undergo MRI scanning
For probable FTLD-tau: a clinical diagnosis of PSP, CBS or nfvPPA, or any clinical FTLD spectrum diagnosis with a proven MAPT mutation
For probable FTLD-TDP: a clinical diagnosis of svPPA or any clinical FTLD spectrum diagnosis with a proven GRN mutation or C9orf72 repeat expansion
For presymptomatic mutation carriers: a MAPT mutation, GRN mutation or a C9orf72 mutation without clinical sign of a FTLD spectrum phenotype (CDR 0) For control subjects: no known neurological or psychiatric disorder
For controls: no known neurological or psychiatric disorder

Exclusion criteria

Other neurological or psychiatric disorder that may affect cognitive functions, such as a brain tumour, multiple sclerosis or drug or alcohol abuse or use of psycho-active medications
CSF profile (β-amyloid, p-tau, t-tau) suggestive of AD pathology
Clinical dementia Rating Scale (CDR) score >1
Contra-indication to undergo MRI
Contra-indication to undergo lumbar puncture

Trial design

110 participants in 4 patient groups

Patients with probable FTLD-tau

Description:

clinical diagnosis of PSP, CBS, or nfvPPA, or any clinical FTLD spectrum diagnosis with a proven MAPT mutation

Treatment:

Diagnostic Test: CSF

Diagnostic Test: Clinical measures

Diagnostic Test: Blood withdrawal

Diagnostic Test: 7T MRI scan

Diagnostic Test: Neuropsychological assessment

Patients with probable FTLD-TDP

Description:

a clinical diagnosis of svPPA, FTLD-ALS or any clinical FTLD spectrum diagnosis with a proven GRN mutation or C9orf72 HRE

Treatment:

Diagnostic Test: CSF

Diagnostic Test: Clinical measures

Diagnostic Test: Blood withdrawal

Diagnostic Test: 7T MRI scan

Diagnostic Test: Neuropsychological assessment

At-risk individuals

Description:

Healthy individuals with a first degree relative with a MAPT or GRN mutation or C9orf72 HRE. These subjects therefore all have a 50% risk to carry one of these genetic variants and develop FTLD later in life.

Treatment:

Diagnostic Test: CSF

Diagnostic Test: Clinical measures

Diagnostic Test: Blood withdrawal

Diagnostic Test: 7T MRI scan

Diagnostic Test: Neuropsychological assessment

Healthy controls

Description:

Healthy individuals without increased risk to develop FTLD

Treatment:

Diagnostic Test: CSF

Diagnostic Test: Clinical measures