Parkinson's DiseaseNCT02952391
Assessing Cholinergic Innervation in Parkinson's Disease Using the PET Imaging Marker [18F]Fluoroethoxybenzovesamicol
An observational study of Parkinson's Disease, run by University Medical Center Groningen at 1 site in Netherlands.
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… Read more about this study
- Who is it for?
- Ages 45 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- [18F] FEOBV PET scan
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2016to Feb 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Two groups of subjects will be included in the study: * Patients with Parkinson's disease * Age-matched healthy control subjects A total of 20 subjects will be included in the study, with 10 subjects in each group.
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Groningen
Groningen, Provincie Groningen, 9713 RB
About this study
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
Read the detailed 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.
- Conditions
- Parkinson's Disease
- Being tested
- [18F] FEOBV PET scan
- Keywords
- cognition, cholinergic system
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F] FEOBV PET scanOther
Cholinergic PET scan with the tracer [18F]Fluoroethoxybenzovesamicol
| Study group | Role | What they receive |
|---|---|---|
| Parkinson's disease patients | patients with Parkinson's disease, between the ages of 45 and 65, with a disease duration of 3 - 10 years Receives: Other: [18F] FEOBV PET scan | |
| healthy control subjects | Healthy control subjects, between the ages of 45 and 65 Receives: Other: [18F] FEOBV PET scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
[18F]FEOBV binding
the difference in VAChT brain binding on a [18F]FEOBV PET-scan between PD patients and healthy control subjects.
Measured: baseline
Secondary outcomes (2)
Test-retest reliability
The percentage change in mean Standardized Uptake Value (SUV) between test and retest to assess test-retest variability.
Measured: one week
Neuropsychological performance
short neuropsychological assessment
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2016 (estimated)
- Study startSep 2016
- Primary completionFeb 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Teus van Laar, University Medical Center Groningen
- Investigators
- Teus van Laar, Prof. Dr., Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02952391
- Sponsor's protocol ID
- NL56173.042.15
- Status last verified
- Nov 2016
- First submitted
- 31 Oct 2016
- Last updated
- 29 Nov 2016
- Results posted
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing Cholinergic Innervation in Parkinson's Disease Using the PET Imaging Marker [18F]Fluoroethoxybenzovesamicol
- ClinicalTrials.gov ID
- NCT02952391
- Acronym / sponsor ID
- NL56173.042.15
- Conditions
- Parkinson's Disease
- Keywords
- cognition, cholinergic system
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Study start
- Sep 2016
- Primary completion
- Feb 2017 (estimated)
- First posted
- 2 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed 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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Parkinson's disease patients | – | Other: [18F] FEOBV PET scanpatients with Parkinson's disease, between the ages of 45 and 65, with a disease duration of 3 - 10 years |
| healthy control subjects | – | Other: [18F] FEOBV PET scanHealthy control subjects, between the ages of 45 and 65 |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Two groups of subjects will be included in the study: * Patients with Parkinson's disease * Age-matched healthy control subjects A total of 20 subjects will be included in the study, with 10 subjects in each group.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F] FEOBV PET scanCholinergic PET scan with the tracer [18F]Fluoroethoxybenzovesamicol | Other | Parkinson's disease patients, healthy control subjects |
Primary outcome
[18F]FEOBV binding
Time frame: baseline
the difference in VAChT brain binding on a [18F]FEOBV PET-scan between PD patients and healthy control subjects.
2 secondary outcomes
Test-retest reliability
Time frame: one week
Neuropsychological performance
Time frame: baseline
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2016.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Teus van Laar, Prof. Dr. principal investigator
University Medical Center Groningen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Parkinson's Disease, run by University Medical Center Groningen at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sygrid van der Zee, MSc (+3153614524, s.van.der.zee01@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[18F]FEOBV binding (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2016.