Clinical Laboratory Evaluation of Chronic Autonomic Failure
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|ClinicalTrials.gov Identifier: NCT03648905|
Recruitment Status : Recruiting
First Posted : August 28, 2018
Last Update Posted : June 10, 2019
The autonomic nervous system controls automatic body functions. Researchers want to improve the tests used to diagnose autonomic failure. Orthostatic hypertension is a drop in blood pressure when a person stands up. Researchers want to focus on this sign of autonomic failure.
To improve testing for conditions that cause autonomic nervous system failure.
People ages 18 and older in one of these categories:
- Their blood pressure drops when they get up.
- They have had a heart transplant or bilateral endoscopic thoracic sympathectomies or have had or will have renal sympathetic ablation
All participants will be screened with:
- Medical history
- Physical exam
- Blood and urine tests
Some participants will be screened with:
- Heart and breathing tests
- IV placement into an arm vein
- Tilt table testing: Participants lie on a table that tilts while an IV is used to draw their blood.
Participants may stay in the hospital for up to 1 week depending on their tests. Tests may include repeats of screening tests and:
- Sweat testing: A drug is placed on the skin to cause sweating. Sensors on the skin measure moisture.
- Lumbar puncture: A needle is inserted between the bones in the back to collect fluid.
- MRI and PET/CT scan: Participants lie on a table that slides into a scanner. For the PET/CT, a small amount of a radioactive chemical will be injected with a small amount of a radioactive chemical.
- Bladder catheter placement to collect urine
- Skin biopsies: A punch tool removes a small skin sample.
- Tests to see how the pupils react to light
- Smelling tests
- Thinking and memory tests
Participants may have a visit about 2 years later to repeat tests.
|Condition or disease|
|Parkinson's Disease Multiple System Atrophy Autonomic Failure|
In dysautonomias, altered functions of one or more components of the autonomic nervous system adversely affect health. A subset of dysautonomias consists of chronic autonomic failure (CAF) syndromes. A key sign of CAF is orthostatic hypotension (OH) due to sympathetic neurocirculatory failure (neurognic OH, or nOH). Primary CAF has been classified based on clinical manifestations into three forms-pure autonomic failure (PAF), multiple system atrophy (MSA), and Parkinson s disease with OH (PD+OH). All three forms involve deposition of the protein, alpha-synuclein (AS), in neurons (PD, PAF) or glial cells (MSA) and therefore are called autonomic synucleinopathies. Clinical assessment alone often is inadequate for distinguishing among these conditions in individual patients. Dementia with Lewy bodies (DLB) is another form of autonomic synucleinopathy. This observational study continues and expands on Protocol 03-N-0004, Clinical Laboratory Evaluation of Primary Chronic Autonomic Failure. The objective is to conduct multi-modality testing of catecholaminergic and autonomic systems in patients with neurodegenerative chronic
autonomic failure (CAF). The goals are to: (a) build up rosters of well characterized patients for future experimental therapeutic trials; (b) test predictions derived from the catecholaldehyde hypothesis for the pathogenesis of autonomic synucleinopathies; (c) follow the natural history of neurodegenerative chronic autonomic failure (CAF); and (d) discover new clinical entities involving catecholaminergic neurodegeneration.
The study population consists of patients with neurodegenerative chronic autonomic failure (neurodegenerative CAF) identified by on site screening at the NIH Clinical Center. Comparison groups include a group on control patients with iatrogenic CAF (e.g., status-post cardiac transplantation, pre/post renal sympathetic ablation, pre/post bilateral thoracic sympathectomies) or PD and without OH (PD No OH), and a group of Healthy Volunteers (HVs), some of whom have genetic abnormalities known to increase the risk of developing PD. A group of MSA patients is included, to build up a subject roster for a planned clinical trial.
This is an observational pathophysiology/natural history study with a planned duration of 3 years. Descriptive statistics will be done in diagnostic groups with neurodegenerative CAF.
The primary outcome measure is results of clinical laboratory research tests in neurodegenerative CAF patients. 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). Correlation analyses will be done among individual values for outcome measures. A secondary outcome measure is estimated non-specific binding of 11C-methylreboxetine, based on studies of patients with iatrogenic CAF and desipraminetreated HVs.
|Study Type :||Observational|
|Estimated Enrollment :||140 participants|
|Official Title:||Clinical Laboratory Evaluation of Chronic Autonomic Failure|
|Actual Study Start Date :||September 6, 2018|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Control patients (iatrogenic CAF)
Patients with iatrogenic chronic autonomic failure (CAF) (e.g., status-post cardiac transplantation, pre/post renal sympathetic ablation, pre/post bilateral thoracic sympathectomies)
Control patients (PD No OH)
Patients with Parkinson's disease (PD) without orthostatic hypotension (PD no OH
Healthy Volunteers, includes people with genetic risk of PD
Patients with neurodegenerative chronic autonomic failure (CAF
Includes patients with orthostatic hypotension (OH) due to sympathetic neurocirculatory failure (nOH), and people with multiple system atrophy (MSA).
- Pathophysiological classification based on clinical laboratory test results [ Time Frame: Initial Visit and on an approximately biennial basis ]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 non-specific binding of 11C-methylreboxetine [ Time Frame: Initial Visit ]Estimated non-specific binding of 11C-methylreboxetine is based on studies of patients with iatrogenic CAF and desipramine-treated HVs
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03648905
|Contact: Janna Gelsomino, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||David S Goldstein, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|