Clearance Mechanisms in Atypical Neurodegenerative Diseases

NCT ID: NCT05317871

Last Updated: 2023-03-09

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-04-01
• Study Completion Date: 2024-04-30

Brief Summary

The project PeptiClear aims to investigate whether the blood-brain-barrier (BBB) and the glymphatic system are compromised in atypical neurodegenerative diseases, and whether Alzheimer´s disease (AD)-related copathology, vascular lesions or sleep disturbances modify the clinical picture or structural and/or functional features of the diseases.

Detailed Description

It is well established for the frequent sporadic (non-genetic) variant of Alzheimer´s disease (AD) that not the overproduction of a specific protein (Amyloid-beta - Aβ) is a major cause but rather the insufficient clearance of this protein from the central nervous system. On one hand, under physiological conditions, the interplay of the several cell types (cerebral endothelial cells, perivascular mural cells (pericytes), glial cells (astrocytes and microglia) and neurons) regulates the neuronal and glial cell environment and is crucial for cell function and survival. On the other hand, Aβ aggregates lead to BBB damage and activation of microglial cells. The BBB facilitates the clearance of proteins such as Aβ via the cerebrovascular system, but its association with other intracerebral Aβ drainage systems, such as the glympathic system, remains to be clarified. As the glymphatic system is mainly active during sleep, sleep disturbances could influence the clinical course. Concerning atypical neurodegenerative diseases, it is not clear whether tau or alpha-synuclein (alpha-syn) deposits also have a potential to damage the BBB. In AD Aβ aggregation and vascular changes give rise to insufficient protein clearance and thus contribute to AD pathogenesis in a synergistic fashion. However the role of copathology in atypical neurodegenerative diseases - which mainly consists of Alzheimer-related changes and vascular pathology - is elusive and remains to be clarified.

The prospective study cohort (N ~80) will include patients with Lewy Body spectrum disease, progressive supranuclear palsy, corticobasal syndrome and frontotemporal dementia. All study participants will undergo a detailed clinical and neuropsychological assessment according to a standardised protocol (i.a. magnet resonance imaging (MRI), positron emission tomography (PET), cerebrospinal fluid (CSF), actigraphy).

Conditions

Neurodegenerative Diseases; Frontotemporal Degeneration

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Lewy Body Spectrum Diseases

No interventions assigned to this group

Progressive Supranuclear Palsy

No interventions assigned to this group

Corticobasal Syndrome

No interventions assigned to this group

Frontotemporal Degeneration

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Atypical Parkinsonian Disorders or Frontotemporal Dementia
• Able to provide written informed consent
• Unchanged pharmacotherapy within 4 days prior to the study specific assessments
• Fluent in German

Exclusion Criteria

• Unable to give informed consent or has a legal guardian
• Other severe mental disorder, e.g. schizophrenia or bipolar affective disorder
• Clinically relevant depression
• Acute suicidality
• Current alcohol, drug or medication abuse
• History of severe traumatic brain injury within 3 months prior to inclusion
• Structural lesions of the basal ganglia or brain stem
• Severe neurological disorder including (but not limited to) epilepsy, systemic disorders, stroke, repeated transient ischaemic attacks, increased brain intracranial pressure, normal pressure hydrocephalus
• Severe medical disorders including (but not limited to) heart failure, respiratory failure, uncontrolled severe arterial hypertension
• Electronic implants (e.g. cardiac pacemaker) or other MRI contraindication
• Renal failure > stage 3 (GFR < 30 mL/min)
• Pregnancy
• Unresolved malignancies within two years prior to inclusion
• Severe current infections or other chronic or systemic disorders
• Other circumstances which preclude participation based on the investigator's judgement

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ludwig-Maximilians - University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Robert Perneczky

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Perneczky, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Klinik und Poliklinik für Psychiatrie und Psychotherapie des LMU Klinikums

Locations

Klinik und Poliklinik für Psychiatrie und Psychotherapie des LMU Klinikums

München, Bavaria, Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Robert Perneczky, Prof. Dr.

Role: CONTACT

PSY.Alzheimerzentrum@med.uni-muenchen.de

+4989440055863

Lena Burow, M.Sc.

Role: CONTACT

lena.burow@med.uni-muenchen.de

+4989440055898

Facility Contacts

Robert Perneczky, Prof. Dr.

Role: primary

psy.alzheimerzentrum@med.uni-muenchen.de

+49 89 4400 55863

Lena Burow, M.Sc.

Role: backup

lena.burow@med.uni-muenchen.de

+49 89 4400 55898

Other Identifiers

21-0106

Identifier Type: -

Identifier Source: org_study_id