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

NCT ID: NCT04246437

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-02-04
• Study Completion Date: 2026-02-01

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

[18F]F-DOPA

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

Group Type: EXPERIMENTAL

[18F]FDOPA

Intervention Type: 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.

Carbidopa 200mg oral dose

Intervention Type: 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.

Entacapone 400mg oral dose

Intervention Type: 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.

Interventions

[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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Lodosyn; Comtan

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Daniel Claassen

OTHER

Sponsor Role: lead

Responsible Party

Daniel Claassen

Professor of Neurology

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Daniel O Claassen, MD, MS

Role: CONTACT

daniel.claassen@vumc.org

615-936-1007

Kaitlyn O'Rourke, MS

Role: CONTACT

katie.orourke@vumc.org

Other Identifiers

192021

Identifier Type: -

Identifier Source: org_study_id