Visualising Cerebral and Peripheral Cholinergic Nerves in Patients With Dementia Lewy Bodies.

NCT04291144 | Completed

• 1 other identifier: DLB-FEOBV
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Lewy Body Dementia (DLB) is the second most common type of neurodegenerative dementia and characterized by loss of cholinergic neurons in the cerebrum and possibly also internal organs. A novel tracer, 18F-fluoroethoxybenzovesamicol (18F-FEOBV), binds to the cholinergic vesicle transporter, a protein expressed uniquely in the vesicles of cholinergic pre-synapses. Our aim is to investigate the cholinergic denervation in patients with DLB using 18F-FEOBV. The investigators plan to recruit 30 patients with DLB and 20 healthy controls to extensive cognitive assessment, computed and positron emission topography, magnetic resonance imaging, and samples of blood. The investigators hypothesize that patients with DLB, compared to controls, have decreased cholinergic innervation in cortical and subcortical areas of the brain, intestines and heart, and that the denervation corresponds to symptoms of autonomic and cognitive dysfunction.

Conditions

Dementia With Lewy Bodies; Degeneration Nerves; Positron-Emission Tomography; Acetylcholine

Outcome Measures

Primary Outcomes (3)

• Cerebral density of vesicular acetylcholine transporter in patients compared to controls

  Average density will be determined in each group for relevant areas of the brain. Group differences will be calculated

  Day 1

• Organ density of vesicular acetylcholine transporter in patients compared to controls

  Average density will be determined in each group for intestine, pancreas, suprarenal gland, and heart. Group differences will be calculated

  Day 1

• Density of vesicular acetylcholine transporter compared to cognitive profile and autonomic symptoms.

  Obtain clinical information and perform standard neurologic and somatic evaluation and full neuropsychological assessment. Relate density of tracer in brain and organs to corresponding cognitive and autonomic symptoms.

  Day 2

Study Arms (2)

Patients

Inclusion criteria are mild to moderate DLB, age above 50, ability to give informed consent.

Radiation: PET-CT using FEOBV; Radiation: MRI-scan; Diagnostic Test: Cognitive assessment; Diagnostic Test: Clinical assessment

Healthy controls

Age above 50.

Radiation: PET-CT using FEOBV; Radiation: MRI-scan; Diagnostic Test: Cognitive assessment; Diagnostic Test: Clinical assessment

Interventions

PET-CT using FEOBV RADIATION

We will inject 300 MBq of 18F-FEOBV in a peripheral vein and scan the internal organs from (0-70 minutes). The patient then rests, and from 180-210min after injection, we will scan the brain on our Siemens High Resolution Research Tomograph.

Healthy controls; Patients

MRI-scan RADIATION

All patients will have an MRI scan of the brain. T1-weighted images will be used to assess general anatomy and identify white matter. T2-weighted sequences will be performed to quantify competing brain pathology. Also, we will collect functional MRI data.

Healthy controls; Patients

Cognitive assessment DIAGNOSTIC_TEST

Full neuropsychometric examination including tests in 5 cognitive domains.

Healthy controls; Patients

Clinical assessment DIAGNOSTIC_TEST

Age, sex, duration of disease, patient history and full somatic and neurological examinations. Constipation assessed with Rome-III criteria. Evaluation of Rapid Eye Movement (REM) sleep Behaviour Disorder (RBDSQ) questionnaire. Test for orthostatic hypotension, heart rate variability, and deep breathing.

Healthy controls; Patients

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with DLB will be recruited from neurological and psychiatric departments in Denmark. Healthy controls will be recruited by advertising in local news papers.

You may qualify if:

• mild to moderate DLB, ability to give informed consent, and typical signs of DLB on an FDG-PET or dopamine transporter (DaT)-scan

You may not qualify if:

• schizophrenia, bipolar disorder, cerebral neoplasms, clinical stroke, diabetes, peripheral neuropathy, previous surgery or radiotherapy on cerebrum or internal organs, gastrointestinal inflammatory disease, severe organ failure, allergy to CT-contrast media and contraindications to MRI-scans

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

Department of Nuclear medicine and PET, Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Related Publications (1)

• Nejad-Davarani S, Koeppe RA, Albin RL, Frey KA, Muller MLTM, Bohnen NI. Quantification of brain cholinergic denervation in dementia with Lewy bodies using PET imaging with [18F]-FEOBV. Mol Psychiatry. 2019 Mar;24(3):322-327. doi: 10.1038/s41380-018-0130-5. Epub 2018 Aug 6. No abstract available.

  PMID: 30082840 BACKGROUND

MeSH Terms

Conditions

Lewy Body Disease; Nerve Degeneration

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Dementia; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Per Borghammer, MD, DMSc

  University of Aarhus

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: March 2, 2020
• Study Start: February 1, 2020
• Primary Completion: March 1, 2023
• Study Completion: March 1, 2023
• Last Updated: May 22, 2023

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)