Assessing Cholinergic Innervation in Parkinson's Disease Using the PET Imaging Marker [18F]Fluoroethoxybenzovesamicol

Parkinson's Disease Clinical Trial

Official title:

Assessing Cholinergic Innervation in Parkinson's Disease Using the PET Imaging Marker [18F]Fluoroethoxybenzovesamicol

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02952391
• Other study ID #: NL56173.042.15
• Status: Recruiting
• Phase: N/A
• First received: October 31, 2016
• Last updated: November 28, 2016
• Start date: September 2016

Study information

• Verified date: November 2016
• Source: University Medical Center Groningen
• Contact: Sygrid van der Zee, MSc
• Phone: +3153614524
• Email: s.van.der.zee01[@]umcg.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial Summary

Although PD is considered predominantly as a motor disease caused by loss of dopaminergic neurons, multiple studies indicate that cholinergic dysfunction already starts in early PD and is crucial for the development of dementia in addition to motor symptoms.Because of its crucial role in CNS functioning and neurodegenerative disorders, including PD, it is of great importance to get a better understanding of the cholinergic functioning in the brain. Pathways of acetylcholine synthesis, transport and release provide possible targets for in vivo imaging of the cholinergic system. However,previous approaches are considered as indirect biomarkers of cholinergic terminal integrity because they measure both pre- and post-synaptic expressions. The novel vesicular acetylcholine transporter (VAChT) tracer [18F]Fluoroethoxy-Benzovesamicol ([18F]FEOBV) provides a more direct measurement of presynaptic cholinergic function. The use of [18F]FEOBV as a Positron Emission Tomography (PET) imaging marker of cholinergic innervations has, however, only been studied in healthy human volunteers and no data is available on patients.

With this study the differences in cholinergic function between PD patients and healthy aged-matched volunteers will be quantified. In addition the test-retest variability will be determined

Description:

Rationale:

Cholinergic neurons play an important role in neurotransmission within the central nervous system (CNS). They are involved in complex functions like memory, learning, recognition, attention, consciousness, regulation of sleep-wake cycles and maintenance of posture and gait. Cholinergic neuron degeneration in the neocortex and hippocampus of the CNS, is an important neurochemical change observed in several neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD). Therefore, assessment of the vesicular acetylcholine transporter (VAChT) as an important molecular target in the cholinergic circuit, has sparked interest in the development of radiotracers for studying this target in vivo. Preclinical studies show the VAChT tracer (-)-5- [18F]Fluoroethoxybenzovesamicol ([18F]FEOBV) to be potentially useful in detecting cholinergic lesions in vivo. A previous [18F]FEOBV PET study confirms that the tracer binds to VAChT with the expected in vivo human brain distribution. The use of [18F]FEOBV as a PET imaging marker of cholinergic innervations has, however, only been studied in healthy human volunteers and no data is available on patients.

Objective:

The main objective of this study is to evaluate the differences in [18F]FEOBV binding between PD patients and healthy control subjects, in order to evaluate the clinical feasibility of [18F]FEOBV as a cholinergic imaging ligand in PD. Secondary objectives are the assessment of test-retest variability and confirming previous findings on [18F]FEOBV validation. Both secondary objectives are prerequisites for the main objective. In addition, an explorative analysis of the relationship between neuropsychological performance and cholinergic innervation will be performed.

Study design: In order to establish the difference in [18F]FEOBV binding between PD patients and healthy control subjects, the study will be conducted in three parts.

• The first part of the study is to establish [18F]FEOBV as a PET tracer for application in clinical research by confirming previous findings on [18F]FEOBV validation. This will include dynamic scanning of 3 healthy control subjects in 3 imaging sessions (0-120, 150-180, 210-240 min after injection of [18F]FEOBV). From this part of the study, the optimal short static scan period will be determined by comparing relative uptake values with the results of kinetic analysis.

• Part 2 of the study is to evaluate differences in [18F]FEOBV in Parkinson's disease and healthy controls. For this, the three dynamic scans of part 1 will be used and an additional 7 healthy control subjects and 10 PD patients will be included for a simple static scan (period determined after part 1 of the study).

• In part 3, test-retest variability is evaluated in both groups. Of each group, 5 patients will undergo a short second static scan.

All subjects will be screened within 30 days before the PET scan for demographic information and detailed clinical history.

Study population:

In total, 10 PD patients and 10 age matched control subjects will be included in the study, all between the ages of 45-65 years. Of the 10 control subjects, 3 will undergo full dynamic scanning, all other subjects included will undergo simple static scanning. A total of 10 subjects, 5 from each group, will undergo a second static scan. The patient group includes patients with Parkinson's disease with a disease duration of at least 3 years and maximum 10 years. All subjects will undergo a neuropsychological assessment.

Main study parameters/endpoints:

The main endpoint of this study is the difference in VAChT brain binding on a [18F]FEOBV PET-scan between PD patients and healthy control subjects.

Secondary endpoints are test-retest variability in both patients and healthy control subjects, and neuropsychological performance in both groups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. primary completion date: February 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 45 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosis Parkinson's disease (for patient group only)

• Disease duration between 3 and 10 years. (for patient group only)

• Age between 45 - 65 years

• Willingness to cooperate and sign written informed consent

• Able and fit enough to participate in this study

Exclusion Criteria:

• The refusal to be informed about an unforeseen clinical finding

• Pregnant women, breast feeding

• Participation in scientific research using radioactivity in the past 12 months , exceeding the maximum annual radiation dose

• Anticoagulant medication, antiplatelet agents used in the 5d before the imaging visit

• Contra-indication for MRI-scanning (metal parts in the body, red pigments in the skin as used in some tattoos)

• Other neurological conditions, more specifically neurodegenerative disorders and brain lesions.

• Treatment with deep brain stimulation

• prior history of neurologic or psychiatric illness (healthy control group only)

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Other:
• [18F] FEOBV PET scan
Cholinergic PET scan with the tracer [18F]Fluoroethoxybenzovesamicol

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	[18F]FEOBV binding	the difference in VAChT brain binding on a [18F]FEOBV PET-scan between PD patients and healthy control subjects.	baseline	No
Secondary	Test-retest reliability	The percentage change in mean Standardized Uptake Value (SUV) between test and retest to assess test-retest variability.	one week	No
Secondary	Neuropsychological performance	short neuropsychological assessment	baseline	No