[18F]F-DOPA Imaging in Patients With Autonomic Failure

Parkinson Disease Clinical Trial

Official title:

[18F]F-DOPA Imaging in Patients With Autonomic Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04246437
• Other study ID #: 192021
• Status: Recruiting
• Phase: Phase 1
• Start date: February 4, 2020
• Est. completion date: February 1, 2025

Study information

• Verified date: September 2023
• Source: Vanderbilt University Medical Center
• Contact: Daniel O Claassen, MD, MS
• Phone: 615-936-1007
• Email: daniel.claassen[@]vumc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Alpha-synucleinopathies refer to age-related neurodegenerative and dementing disorders, characterized by the accumulation of alpha-synuclein in neurons and/or glia. The anatomical location of alpha-synuclein inclusions (Lewy Bodies) and the pattern of progressive neuronal death (e.g. caudal to rostral brainstem) give rise to distinct neurological phenotypes, including Parkinson's disease (PD), Multiple System Atrophy (MSA), Dementia with Lewy Bodies (DLB). Common to these disorders are the involvement of the central and peripheral autonomic nervous system, where Pure Autonomic Failure (PAF) is thought (a) to be restricted to the peripheral autonomic system, and (b) a clinical risk factor for the development of a central synucleinopathy, and (c) an ideal model to assess biomarkers that predict phenoconversion to PD, MSA, or DLB. Such biomarkers would aid in clinical trial inclusion criteria to ensure assessments of disease- modifying strategies to, delay, or halt, the neurodegenerative process. One of these biomarkers may be related to the neurotransmitter dopamine (DA) and related changes in the substantia nigra (SN) and brainstem. [18F]F-DOPA is a radiolabeled substrate for aromatic amino acid decarboxylase (AAADC), an enzyme involved in the production of dopamine. Use of this radiolabeled substrate in positron emission tomography (PET) may provide insight to changes in monoamine production and how they relate to specific phenoconversions in PAF patients. Overall, this study aims to identify changes in dopamine production in key regions including the SN, locus coeruleus, and brainstem to distinguish between patients with PD, MSA, and DLB, which may provide vital information to predict conversion from peripheral to central nervous system disease.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: February 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients with a diagnosis if pure autonomic failure

2. Patients with autonomic failure and possible PD, MSA, or DLB

3. Healthy adults aged 18 and above

4. Clinical exam confirming clinical designation

Exclusion Criteria:

• Subjects who have any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g., cochlear implants, pacemakers, neurostimulators, biostimulators, electronic infusion pumps, etc.), because such devices may be displaced or malfunction.
• Subjects who have any type of ferromagnetic bioimplant that could potentially be displaced.
• Subjects who have cerebral aneurysm clips.
• Subjects who may have shrapnel imbedded in their bodies (such as from war wounds), metal workers and machinists (potential for metallic fragments in or near the eyes).
• Subjects who are pregnant, because the effects of high field MRI on fetuses are not yet known.
• Minors (younger than 18 years)

Also excluded are subjects incapable of giving informed written consent:

• Subjects who cannot adhere to the experimental protocols for any reason, or have an inability to communicate with the researcher.
• Subjects who have limited mental ability to give informed consent, mentally retarded, altered mental status, mental disability, confusion, or psychiatric disorders.
• Prisoners

Related Conditions & MeSH terms

• Autonomic Failure
• Dementia With Lewy Bodies
• Lewy Body Disease
• Multiple System Atrophy
• Parkinson Disease
• Pure Autonomic Failure
• Shy-Drager Syndrome

Intervention

Drug:
• [18F]FDOPA
Patients will receive a 3-D emission scan following a 6-8 mCi slow bolus injection of [18F]FDOPA over a 30 second period. Serial scans are started simultaneously with the bolus injection of radiotracer and are obtained for approximately 95 minutes.
• Carbidopa 200mg oral dose
30 minutes prior to the PET scan, patients will receive the 200mg oral dose of carbidopa to prevent peripheral [18F]FDOPA metabolism to increase signal-to-noise ratio of the imaging.
• Entacapone 400mg oral dose
30 minutes prior to the PET scan, patients will receive the 400mg oral dose of entacapone to prevent peripheral [18F]FDOPA metabolism to increase signal-to-noise ratio of the imaging.

Locations

Country	Name	City	State
United States	Vanderbilt University Medical Center	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Daniel Claassen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences in FDOPA uptake across patient populations	Specific FDOPA uptake, Ki, will be calculated via a reference Logan plot to provide voxelwise measurements of FDOPA uptake. Mean uptake will be assessed in brain regions-of-interest in 40 participants to assess potential differences across different autonomic failure-related diseases.	95 minutes post-PET after start of PET imaging