Clinical Laboratory Evaluation of Chronic Autonomic Failure

NCT03648905 | Active Not Recruiting FDA Drug

• 2 other identifiers: 18014018-N-0140
• Study Type: observational
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease; Multiple System Atrophy; Autonomic Failure

Keywords

Autonomic Failure; Parkinson's Disease; Multiple System Atrophy; Lewy Body; Catecholamines

Outcome Measures

Primary Outcomes (1)

• Results of clinical laboratory research tests

  Neurobehavioral rating scales include the University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Uniform Parkinson s Disease Rating Scale (UPDRS). Neurochemical data are from assays of catechols and related compounds in plasma or cerebrospinal fluid. Neuroimaging data are from 18F-DOPA, 18Fdopamine, 13Nammonia, and 11Cmethylreboxetine positron emission tomographic (PET) scanning and MRI. Immunofluorescence microscopy is used to quantify immunoreactive tyrosine hydroxylase and AS in skin biopsy samples.

  Initial Visit and on an approximately biennial basis

Study Arms (4)

Control patients (iatrogenic CAF)

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

Drug: 13N-Ammonia; Drug: 18F-DOPA; Drug: 11C-Methylreboxetine (11C-MRB); Drug: 18F-Dopamine

Control patients (PD No OH)

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

Drug: 13N-Ammonia; Drug: 18F-DOPA; Drug: 11C-Methylreboxetine (11C-MRB); Drug: 18F-Dopamine

Healthy Volunteers

Healthy Volunteers, includes people with genetic risk of PD or studied as concurrent controls

Drug: 13N-Ammonia; Drug: 18F-DOPA; Drug: 11C-Methylreboxetine (11C-MRB); Drug: 18F-Dopamine

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).

Drug: 13N-Ammonia; Drug: 18F-DOPA; Drug: 11C-Methylreboxetine (11C-MRB); Drug: 18F-Dopamine

Interventions

13N-Ammonia DRUG

a perfusion imaging agent

Control patients (PD No OH); Control patients (iatrogenic CAF); Healthy Volunteers; Patients with neurodegenerative chronic autonomic failure (CAF)

18F-DOPA DRUG

is a positron-emitting analog of the catechol amino acid, levodopa

Control patients (PD No OH); Control patients (iatrogenic CAF); Healthy Volunteers; Patients with neurodegenerative chronic autonomic failure (CAF)

11C-Methylreboxetine (11C-MRB) DRUG

11C-MRB may be injected IV for visualizingsites of neuronal uptake of norepinephrine in the brain or periphery by PET scanning. Setup includes placement of an arm IV catheter. 11C-MRB is a Radioactive Research Drug.

Control patients (PD No OH); Control patients (iatrogenic CAF); Healthy Volunteers; Patients with neurodegenerative chronic autonomic failure (CAF)

18F-Dopamine DRUG

is a positron-emitting analog of the catecholamine, dopamine

Control patients (PD No OH); Control patients (iatrogenic CAF); Healthy Volunteers; Patients with neurodegenerative chronic autonomic failure (CAF)

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of patients with neurodegenerative CAF and patients with MSA. Comparison groups include control patients with iatrogenic CAF, patients with PD without OH (PD No OH), and Healthy Volunteers (HVs).

You may qualify if:

• Patients with heart transplants or pre- or post-bilateral endoscopic thoracic sympathectomies, and
• years or older, and
• Able to provide own consent to participate.
• Patients with PD and no OH who have (a) already been evaluated under other protocols of the AMS and are undergoing follow-up; (b) have already been evaluated under another intramural NINDS protocol; or (c) have cardiac symptoms, signs, or laboratory findings that in the opinion of the PI make it likely there is a cardiac sympathetic lesion, and
• years or older, and
• Able to provide own consent to participate.
• Age 18 years or older, and
• Able to provide own consent to participate.
• NIH employees may participate. There is no direct solicitation of employees/staff by supervisors. Co-workers will not solicit co-workers. NIH employees are required to abide by NIH Policy Manual 2300-630-3, "Leave Policy for NIH Employees Participating in NIH Medical Research Studies."
• Patient Group Referred for Orthostatic Hypotension
• A medical condition that in the judgment of the Principal Investigator would place the subject at substantially increased acute medical risk, or
• A disqualifying condition such as: hepatic or renal failure, symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, currently symptomatic coronary heart disease, cerebrovascular disease with current symptoms (e.g., recent transient ischemic attacks), diabetes, or
• Secondary form of CAF, such as diabetic autonomic neuropathy, or
• Being treated currently (within 2 weeks of anticipated protocol participation) with a medication known to interfere with the cell membrane norepinephrine transporter, which would obviate obtaining scientifically valid results (e.g., tricyclic antidepressant).
• Condition that may cause difficulty or inability to insert a catheter into a vein, or

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Parkinson Disease; Multiple System Atrophy; Pure Autonomic Failure

Interventions

fluorodopa F 18

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases

Study Officials

• Justin Y Kwan, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: August 28, 2018
• Study Start: September 6, 2018
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 29, 2026

Record last verified: 2026-02-20

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)