Amyloid-β Clearance Mechanisms in Alzheimer's Disease

Alzheimer's Disease (AD) Clinical Trial

— AmyClearAD  

Official title:

Amyloid-β Clearance Mechanisms: A Multi-modal Study on Lymphatic, Glymphatic and Blood-brain-barrier Function in Alzheimer's Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05059158
• Other study ID #: 18-606
• Secondary ID: 18-6061081
• Status: Recruiting
• Start date: June 1, 2021
• Est. completion date: June 2024

Study information

• Verified date: October 2023
• Source: Ludwig-Maximilians - University of Munich
• Contact: Robert Perneczky, Prof.Dr.med.
• Phone: +4989440055863
• Email: PSY.Alzheimerzentrum[@]med.uni-muenchen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The focus of this study is to examine the protein-plaque clearance (Aß) in relation to the blood-brain-barrier, the glymphatic system, brain lymphatic system and enzymatic degradation. In order to achieve this aim the investigators intend to study participants with a Subjective Cognitive Decline, Mild Cognitive Impairment and a mild Alzheimer's disease.

Description:

In this study, the investigators want to examine the different mechanisms of the accumulation and the clearance of Aß- deposits with imaging methods. One focus of the study is an improved characterisation of a blood-brain-barrier disorder (which seems to have an impact on the Aß-accumulation). Another main aim is to provide an improved mechanistic clearance model, which integrates crucial components such as the recently proposed cerebral glymphatic and lymphatic pathways, and which addresses the interaction between the different components and their individual contribution to Aβ removal from the brain. A possible connection between sleep and an altered transport mechanism will be analysed. The prospective study cohort (N ~60) will include patients with Mild Cognitive Impairment, mild clinical AD and Subjective Cognitive Decline. All study participants will undergo a detailed clinical and neuropsychological assessment according to a standardised protocol (i.a. MRI, PET, CSF, actigraphy). Follow-up assessments will not be performed in the present project, but are planned in a subsequent study, pending further funding.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

Inclusion Criteria:

• Diagnosis of amnestic MCI or AD dementia or clinical normal

• 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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease (AD)

Intervention

Radiation:
• positron emission tomography (PET)
18-Flutemetamol PET (clinical indicated) is going to be performed at the visit.

Locations

Country	Name	City	State
Germany	Klinik und Poliklinik für Psychiatrie und Psychotherapie des LMU Klinikums	München	Bayern

Sponsors (1)

Lead Sponsor	Collaborator
Ludwig-Maximilians - University of Munich

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in the disruption of the brain-blood-barrier between the subgroups	Name of Measurement: Ktrans; Measurement Tool: DCI sequence (MRI); Unit: min -1	Baseline
Primary	Clearance mechanisms and glymphatic or cerebral lymphatic system	Can a disruption in the cerebral clearance through the glymphatic or cerebral lymphatic system be proven in patients with AD, MCI or SCD?; Name of Measurement: DTI ALPS; Measurement Tool: DTI MRI; Unit: mean (Dxpro, Dypro)/ mean (Dypro, Dzasc)	Baseline
Primary	Connection between the structural/functional connectivity of the resting networks and the clearance mechanisms	Correlations between correlations of bold fluctuations/ number of tracts and DTI ALPS Index	Baseline
Primary	Differences between sleep and activity in SCD, MCI and AD; Do they have a mediator role in association of the BBB disruption and Aß pathology?	Name of Measurement: Sleep Efficiency, Sleep Time, PIM, TAT, ZCM ;Measurement Tool: Actigraphy; Units: minutes, count	Baseline
Primary	Connection between clinical symptoms, Aß pathology and BBB disorder	Correlations between Clinical Dementia Rating Sum of Boxes, CSF markers (pg/ml) and Aß PET, SUVr and Ktrans map	Baseline