Patients with iatrogenic chronic autonomic failure (CAF) (e.g., status-post cardiac transplantation, pre/post renal sympathetic ablation, pre/post bilateral thoracic sympathectomies)

Patients with Parkinson's disease (PD) without orthostatic hypotension (PD no OH)

Healthy Volunteers with genetic risk of PD

Includes patients with orthostatic hypotension (OH) due to sympathetic neurocirculatory failure (nOH), and people with multiple system atrophy (MSA).

Parkinson's Disease

Multiple System Atrophy

Autonomic Failure

18F-DOPA is a positron-emitting analog of the catechol amino acid, levodopa (L-DOPA, Ldihydroxyphenylalanine). 18F-DOPA PET scanning is used to visualize catecholamine terminals in the brain.

18F-Dopa

11C-MRB may be injected IV for visualizing sites of neuronal uptake of norepinephrine in the brain or periphery by PET scanning.

11C-methylreboxetine

13N-labeled ammonia is a perfusion imaging agent used to obtain perfusion-corrected values for 18F-dopamine-derived radioactivity in the heart and other organs.

13N-Ammonia

18F-Dopamine is a positron-emitting analog of the catecholamine, dopamine. 18F- Dopamine positron emission tomographic (PET) scanning may be used to visualize sympathetic innervation.

18F-Dopamne

Desipramine (DMI) is an approved tricyclic antidepressant. The drug inhibits neuronal uptake of catecholamines. DMI treatment is used to test for effects of NET inhibition on results of 11C-MRB or 18F-dopamine PET scans. The subject receives a single dose of DMI by mouth (about 125 mg per 70 kg body mass) about 2-3 hours before the subject receives the PET imaging agent.

Desipramine (DMI)

National Institutes of Health Clinical Center

Clinical Laboratory Evaluation of Chronic Autonomic Failure

Neuroimaging data are from MRI and from 18F-DOPA and 18F-dopamine PET scanning. Neurochemical data are from assays of catechols in plasma and cerebrospinal fluid. Immunofluorescence microscopy data are from analyses of immunoreactive tyrosine hydroxylase and AS in skin biopsy samples. Neurobehavioral rating scale data are from the University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Uniform Parkinson s Disease Rating Scale (UPDRS).

Estimated extraneuronal binding of 11C-methylreboxetine is based on studies of patients with iatrogenic CAF and desipramine-treated HVs

National Institute of Neurological Disorders and Stroke (NINDS)

Placebo administered in pill form once by mouth

100mg levodopa administered in pill form once by mouth

200mg levodopa administered in pill form once by mouth

Placebo administered in pill form once by mouth
Placebo: Sugar pill packaged to resemble levodopa

Placebo

100mg levodopa administered in pill form once by mouth
Levodopa: EIther 100mg or 200 mg, depending on arm assignment, administered once by mouth.

100mg L-DOPA

200mg levodopa administered in pill form once by mouth
Levodopa: EIther 100mg or 200 mg, depending on arm assignment, administered once by mouth.

200mg L-DOPA

Total

Sex: Female, Male

Race (NIH/OMB)

Region of Enrollment

Differential galvanic skin response will be assessed with respect to the conditioned stimulus versus the control stimulus. The investigators will compare, at an aggregate level, the differential galvanic skin response between the placebo, 100 mg, and 200 mg L-DOPA groups.

Galvanic Skin Response

Amygdala is the part of the brain which controls emotions, survival instincts, and memory. PTSD patients exhibit hyperactivity in the amygdala in response to stimuli.
Differential functional activation of the amygdala will be assessed with respect to the conditioned stimulus versus the control stimulus. The investigators will compare, at an aggregate level, the differential functional activation between the placebo, 100 mg, and 200 mg L-DOPA groups.

Percentage Change in Functional Activation of Amygdala

Differential functional activation of the anterior cingulate cortex will be assessed with respect to the conditioned stimulus versus the control stimulus. The investigators will compare, at an aggregate level, the differential functional activation between the placebo, 100 mg, and 200 mg L-DOPA groups.

Functional Activation of Anterior Cingulate Cortex

Overall Study

Josh Cisler

Stress Disorder, Post Traumatic

EIther 100mg or 200 mg, depending on arm assignment, administered once by mouth.

Levodopa

University of Arkansas for Medical Sciences

Dopamine Enhancement of Fear Extinction Learning in PTSD (1R21MH108753)

University of Wisconsin, Madison

Cancer in Children.

Hearing Loss

study of mutations of metabolic enzymes and membrane transport genes, which will be performed by sequencing.

Genetic study

study of mutations of the mitochondrial gene MT-RN1, which will be performed by sequencing.

Genetic study MT-RN1

Institut Curie

Cancer and Hearing Loss Related in Children

Cancer and Deafness Associated With the Use of Platinum Derivatives in Children

Assistance Publique - Hôpitaux de Paris

Treatment with 800 mg - 1200 mg EGCG as putative neuroprotective agent

EGCG as putative neuroprotective agent

Fox trial finder of the Michael J Fox foundation

Neurology Department, Ludwig-Maximilians University

Department of Neurology, Klinikum rechts der Isar, Technische Universität München

Kliniken Beelitz GmbH, Neurologisches Fachkrankenhaus für Bewegungsstörungen

Charité - Universitätsmedizin Berlin

Technische Universität Dresden

Heinrich-Heine-Universität, Neurologische Klinik

Paracelsus-Elena-Klinik Kassel

Universität Leipzig

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Philipps Universität Marburg

Eberhard Karls Universität Tübingen

Universitätsklinikum Ulm

Progression Rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach

Double-blind, Randomised, Placebo-controlled Parallel Group Study to Investigate the Effect of EGCG Supplementation on Disease Progression of Patients With Multiple System Atrophy (MSA)

To assess the efficacy of EGCG vs. Placebo to reduce the progression in the motor examination (ME) of the Unified MSA Rating Scale (UMSARS-ME) from V1 to V7, (80% power, 5% P-level, 50% effect size, i.e. an expected mean yearly UMSARS-ME increase of 3.9 under verum treatment compared to 7.8 ± 6.8 (mean ± standard deviation) under Placebo-treatment.

To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in UMSARS total score

To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in clinical global impression

To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in global and regional cerebral atrophy (3D MP-RAGE MRI volumetry, 3D FLAIR)

To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in global and regional cerebral iron deposition in pons and striatum (T2* MRI)

Clinical safety and tolerability of EGCG (physical and neurological examination, laboratory parameters, adverse events, vital signs, drop-out rates, survival rates and survival time)

To assess any effect of EGCG vs. Placebo on the evolution of the above mentioned parameters during the wash-out phase (from V6 to V7) to explore possible symptomatic effects.

To assess the efficacy of EGCG vs. Placebo to reduce the progression from V1 to V7 in Albumine, total protein, ferritin, iron, transferrin

catechol/atrophie

Clinical Laboratory Evaluation of Chronic Autonomic Failure

Dopamine Enhancement of Fear Extinction Learning in PTSD (1R21MH108753)

Cancer and Hearing Loss Related in Children

Progression Rate of MSA Under EGCG Supplementation as Anti-Aggregation-Approach

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