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NCT Number: NCT06870838

Neuroinflammation in FTLD

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:

1. To elucidate the role and timing of neuroinflammation in FTLD by using a combination of clinical measures, 7T MRI, and CSF biomarkers; 2. To differentiate FTLD-TDP and FTLD-tau during life using biomarkers for neuroinflammation; 3. 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Corticobasal Syndrome(CBS) Aphasia Aphasia, Primary Progressive Basal Ganglia Diseases Behavioral Variant Frontotemporal Dementia (bvFTD) Brain Diseases Central Nervous System Diseases Communication Disorders Corticobasal Degeneration Cranial Nerve Diseases Dementia Eye Diseases Frontotemporal Lobar Degeneration Frontotemporal Lobar Degeneration (FTLD) Inflammation Language Disorders Mental Disorders Metabolic Diseases Movement Disorders Nerve Degeneration Nervous System Diseases Neurobehavioral Manifestations Neurocognitive Disorders Neurodegenerative Diseases Neuroinflammatory Diseases Neurologic Manifestations Nutritional and Metabolic Diseases Ocular Motility Disorders Ophthalmoplegia Paralysis Pathologic Processes Pathological Conditions, Signs and Symptoms Primary Progressive Aphasia(PPA) Progressive Supranuclear Palsy(PSP) Proteostasis Deficiencies Signs and Symptoms Speech Disorders Supranuclear Palsy, Progressive TDP-43 Proteinopathies Tauopathies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Leiden University Medical Center, Leiden, Netherlands

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About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

7T MRI scan

Diagnostic Test

MRI-scanning of the brain using a 7T MRI scanner

CSF

Diagnostic Test

CSF collection via lumbar puncture

Blood withdrawal

Diagnostic Test

Blood is collected by doing a blood withdrawal

Neuropsychological assessment

Diagnostic Test

Tests for memory, language, attention, executive functions, praxis, social cognition, visuoconstructive skills

Clinical measures

Diagnostic Test

Medical history, neurological assessment, neuropsychiatric inventory

Primary outcomes

  1. MR Spectroscopy in the lateral anterior cingulate cortex

    Time frame: At baseline

    MR Spectroscopy data analysis in a single volume of interest in the lateral anterior cingulate cortex to assess changes in metabolites related to neurodegeneration and neuroinflammation. The analysis in LCModel will give us metabolite concentrations for total N-acetyl-aspertate (tNAA), glutamate (Glu), myo-inositol (mI), and total choline compound (tCho).

  2. Diffusion weighted MR spectroscopy in the lateral anterior cingulate cortex

    Time frame: At baseline

    Diffusion weighted MR Spectroscopy data analysis in a single volume of interest in the lateral anterior cingulate cortex to assess changes in the apparent diffusion coefficients of specific metabolites related to neurodegeneration and neuroinflammation. The analysis done in LCModel will give us metabolite apparent diffusion coefficients for total N-acetyl-aspertate (tNAA), glutamate (Glu), myo-inositol (mI), and total choline compound (tCho).

  3. Quantitative susceptibility mapping for iron localization and quantification

    Time frame: At baseline

    Cross-sectional MR analysis to determine iron accumulation in the brain. The analysis will be performed with the SEPIA toolbox to obtain quantitative susceptibility values in various brain regions.

  4. Neurodegeneration biomarkers in blood

    Time frame: At baseline

    Biomarkers for neurodegeneration (neurofilament light chain (NFL), total tau) in blood.

  5. Neurodegeneration biomarkers in CSF

    Time frame: At baseline

    Biomarkers for neurodegeneration (neurofilament light chain (NFL), total tau) in CSF.

  6. Neuroinflammation biomarkers in CSF

    Time frame: At baseline

    Biomarkers for neuroinflammation (YKL-40, TREM-1, TREM-2, IL-1, IL-6, TNF-α, GFAP, CHIT1) in CSF.

  7. Iron accumulation biomarkers in blood

    Time frame: At baseline

    Biomarkers for iron accumulation ( ferritin, and iron) in blood.

  8. Iron acccumulation biomarkers in CSF

    Time frame: At baseline

    Biomarkers for iron accumulation (transferritin, ferritin, and iron) in CSF.

Secondary outcomes

  1. Clinical and neuropsycological evaluation: Clinical dementia rating scale

    Time frame: At baseline and 1 year follow-up

    Cognitive and neuropsychological assessments for clinical dementia rating scale (CDR) to assess the cognitive functioning of the participant. The CDR is a combination score including multiple neuropsychological functioning on multiple domains (memory, language, attention, executive function, praxis, social cognition, and visuoconstructive skills) and clinical evaluation. A score of 0 means not impaired or no symptoms, a score of 0.5 means prodromal, and a score of 1 and higher (up to 3) reflects a symptomatic individual.

  2. Clinical and neuropsycological evaluation: Montreal Cognitive Assessment

    Time frame: At baseline and 1 year follow-up

    Cognitive and neuropsychological assessments for Montreal Cognitive Assessment (MoCA) to assess the cognitive functioning of the participant. A total score of 30 can be obtained. A higher score reflects a better performance. The cut-off point for a normal score is 26. A score lower than 26 reflects impairments or one or more cognitive domains.

  3. Clinical evaluation: Parkinson's Disease Rating Score

    Time frame: At baseline and 1 year follow-up

    Neurological examination for Unified Parkinson's Disease rating score (UPDRS). The score will be between 0 and 260, with a lower score indicating no symptoms and a total score of 260 indicating all symptoms.

  4. Clinical evaluation: Neuropsychiatric assessment

    Time frame: At baseline and 1 year follow-up

    Neuropsychiatric examination with the neuropsychiatric inventory (NPI) to assess psychiatric symptoms. The NPI has a total score range of [0, 144], with a higher score indicating more neuropsychiatric symptoms. A NPI score higher than 0 indicates the presence of one or more symptoms, a score of 4 or higher indicates moderate symptoms.

Other outcomes

  1. 7T MR markers for brain clearance: CSF mobility

    Time frame: At baseline

    Assessment of the CSF mobility in the perivascular spaces throughout the brain using a T2-weighted scan and diffusion weighted scans.

  2. 7T MRI markers for brain clearance: prevalance of perivascular spaces

    Time frame: At baseline

    In this analysis, the visible perivascular spaces on a T2-weighted scan (0.6 x 0.6 x 0.6 mm) will be counted and their volume will be calculated to assess changes in the different groups.

  3. Markers for brain clearance: CSF

    Time frame: At baseline

    Levels of total tau and AQP4

Sponsors and collaborators

Lead sponsor

Leiden University Medical Center

Other

Collaborators

  • Erasmus Medical Center

Registry information

Official study title

Neuroinflammation in Frontotemporal Lobar Degeneration - a Multimodal Biomarker Study

Important dates

Study start
2023
Primary completion
2025
Study completion
2026
First posted
Mar 11, 2025
Registry last updated
Sep 11, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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