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

NCT04246437 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 192021
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Autonomic Failure; Pure Autonomic Failure; Parkinson Disease; Multiple System Atrophy; Dementia With Lewy Bodies

Keywords

FDOPA; PET

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

[18F]F-DOPA

EXPERIMENTAL

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

Drug: [18F]FDOPA; Drug: Carbidopa 200mg oral dose; Drug: Entacapone 400mg oral dose

Interventions

[18F]FDOPA DRUG

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.

[18F]F-DOPA

Carbidopa 200mg oral dose DRUG

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.

Also known as: Lodosyn

[18F]F-DOPA

Entacapone 400mg oral dose DRUG

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.

Also known as: Comtan

[18F]F-DOPA

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with a diagnosis if pure autonomic failure
• Patients with autonomic failure and possible PD, MSA, or DLB
• Healthy adults aged 18 and above
• Clinical exam confirming clinical designation

You may not qualify if:

• 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

Sponsors & Collaborators

• Daniel Claassen: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

RECRUITING

MeSH Terms

Conditions

Pure Autonomic Failure; Parkinson Disease; Multiple System Atrophy; Lewy Body Disease

Interventions

fluorodopa F 18; Carbidopa; entacapone

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dementia; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Methyldopa; Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Hydrazines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Central Study Contacts

Daniel O Claassen, MD, MS

CONTACT

615-936-1007; daniel.claassen@vumc.org

Kaitlyn O'Rourke, MS

CONTACT

katie.orourke@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: January 25, 2020
• First Posted: January 29, 2020
• Study Start: February 4, 2020
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Locations

US (1)