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

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.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease; Multiple System Atrophy; Pure Autonomic Failure; Dementia With Lewy Bodies; Autonomic Failure
• Intervention / Treatment: Drug: [18F]FDOPA; Drug: Carbidopa 200mg oral dose; Drug: Entacapone 400mg oral dose

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Daniel O Claassen, MD, MS; Phone Number: 615-936-1007; Email: daniel.claassen@vumc.org
• Study Contact Backup: Name: Kaitlyn O'Rourke, MS; Email: katie.orourke@vumc.org

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Recruiting
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: [18F]F-DOPA; All patients will receive [18F]F-DOPA for PET imaging to measure pre-synaptic dopamine in the brain.

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.; Drug: 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.; Other Names: Lodosyn; Drug: 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.; Other Names: Comtan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Daniel Claassen

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: January 25, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): March 16, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: PET; FDOPA
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Parkinson Disease; Multiple System Atrophy; Lewy Body Disease; Pure Autonomic Failure; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Catecholamines; Methyldopa; Dihydroxyphenylalanine; Hydrazines; Carbidopa; fluorodopa F 18; entacapone
• Other Study ID Numbers: 192021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No