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

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StatusVrbovanje

Sponzori

Daniel Claassen

KLINIČKO ISPITIVANJE: NCT04246437

BioSeek: nct04246437

Ključne riječi

Sažetak

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.

Datumi

Posljednja provjera:	12/31/2019
Prvo podneseno:	01/24/2020
Predviđena prijava poslana:	01/26/2020
Prvo objavljeno:	01/28/2020
Posljednje ažuriranje poslano:	02/15/2020
Posljednje ažuriranje objavljeno:	02/18/2020
Stvarni datum početka studija:	02/03/2020
Procijenjeni datum primarnog završetka:	01/31/2022
Procijenjeni datum završetka studije:	01/31/2022

Stanje ili bolest

Autonomic Failure

Pure Autonomic Failure

Parkinson Disease

Multiple System Atrophy

Dementia With Lewy Bodies

Intervencija / liječenje

Drug: [18F]F-DOPA

Faza

Faza 1

Grupe ruku

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

Kriterij prihvatljivosti

Dobni uvjeti za studiranje	18 Years Do 18 Years
Spolovi koji ispunjavaju uvjete za studij	All
Prihvaća zdrave volontere	Da
Kriteriji	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

Ishod

Primarne mjere ishoda

1. Differences in FDOPA uptake across patient populations [95 minutes]

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.

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

Ključne riječi

atrophy

lewy body disease

demencija

synucleinopathies

decarboxylase

dopamine