Last updated on September 2018

Clinical Laboratory Evaluation of Chronic Autonomic Failure


Brief description of study

Background

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.

Objective

To improve testing for conditions that cause autonomic nervous system failure.

Eligibility

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
    Design

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
  • Questionnaires

Participants may have a visit about 2 years later to repeat tests.

Detailed Study Description

Objective

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 (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 nOH. The goals are to: (a) build up a roster 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 nOH; and (d) discover new clinical entities involving catecholaminergic neurodegeneration.

Study Population:

The study population consists of patients with nOH identified by on site screening at the NIH Clinical Center. Comparison groups include patients with iatrogenic CAF (e.g., status-post cardiac transplantation, renal sympathetic ablation, bilateral thoracic sympathectomies) and Healthy Volunteers (HVs).

Design

This is an observational pathophysiology/natural history study with a planned duration of 3 years. Descriptive statistics will be done in diagnostic groups with nOH.

Outcome Measures:

The primary outcome measure is results of clinical laboratory research tests in nOH 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.

Clinical Study Identifier: NCT03648905

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National Institutes of Health Clinical Center
Bethesda, MD United States
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