Clinical Trials/NCT03648905

NCT03648905

Active, not recruiting

Not Applicable

Clinical Laboratory Evaluation of Chronic Autonomic Failure

National Institute of Neurological Disorders and Stroke (NINDS)1 site in 1 country89 target enrollmentSeptember 6, 2018

ConditionsParkinson's Disease Multiple System Atrophy Autonomic Failure

Interventions13N-Ammonia 11C-Methylreboxetine (11C-MRB)18F-Dopamine 18F-DOPA

Drugs13N-Ammonia 18F-DOPA 11C-Methylreboxetine (11C-MRB)18F-Dopamine

Overview

Phase: Not Applicable
Intervention: 13N-Ammonia
Conditions: Parkinson's Disease
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
Enrollment: 89
Locations: 1
Primary Endpoint: Results of clinical laboratory research tests
Status: Active, not recruiting
Last Updated: 3 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed Description

Objective: In dysautonomias, altered function 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. This observational study continues and expands on Protocol 03-N-0004, "Clinical Laboratory Evaluation of Primary Chronic Autonomic Failure." The overall objective is to refine and conduct multi-modality testing of catecholaminergic and autonomic systems in patients with CAF. The goals are to: (a) improve the differential diagnosis of CAF via laboratory biomarkers; (b) track the natural history of CAF by follow-up testing; (c) apply clinical laboratory biomarkers to gain insights into underlying pathophysiological mechanisms of CAF; and (d) build up rosters of well characterized patients for future experimental therapeutic trials. Study Population: The study population consists of patients with neurodegenerative CAF identified by on-site screening at the NIH Clinical Center. Comparison groups include control patients with iatrogenic CAF (e.g., status-post cardiac transplantation, pre/post bilateral thoracic sympathectomies) or PD without OH (PD No OH), and Healthy Volunteers (HVs). MSA patients are included, to build up a subject roster for a planned clinical trial. Design: This is an observational pathophysiology/natural history study with a planned duration of 5 years. Descriptive statistics will be done in diagnostic groups with neurodegenerative CAF. Outcome Measures: The study is hypothesis generating/exploratory. The primary outcome measure is 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, 18F-dopamine, 13N-ammonia, and 11C-methylreboxetine positron emission tomographic (PET) scanning and MRI. Immunofluorescence microscopy is used to quantify immunoreactive tyrosine hydroxylase and AS in skin biopsy samples. Correlation analyses are done among individual values for outcome measures.

Registry

clinicaltrials.gov

Start Date

September 6, 2018

End Date

December 31, 2029

Last Updated

3 days ago

Study Type

Observational

Sex

All

Investigators

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•for that patient. Previous enrollment in NIH Clinical Protocol 03-N-0004 is not required for enrollment in this study. We do plan to recruit participation into this study from NIH Clinical Protocol 03-N-0004, which has been closed.
•If a patient has been referred for OH, then the patient gives consent at the NIH Clinical Center (and therefore is accrued) and then has screening testing at the NIH Clinical Center to confirm that the OH is neurogenic. We anticipate that all patients referred for OH will be shown to have nOH upon screening testing at the NIH Clinical Center. At the time of screening, exclusionary abnormal laboratory test results (e.g., high serum creatinine indicating renal failure) may come to light, in which case they will be withdrawn from the study; however, the patient would have been accrued.
•Inclusion criteria: Control patients with iatrogenic CAF
•Patients with heart transplants or pre- or post-bilateral endoscopic thoracic sympathectomies, and
•18 years or older, and
•Able to provide own consent to participate.
•Inclusion criteria: Control patients with PD No OH:
•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
•18 years or older, and
•Able to provide own consent to participate.

Exclusion Criteria

Not provided

Intervention: 18F-DOPA

Healthy Volunteers

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

Intervention: 11C-Methylreboxetine (11C-MRB)

Outcomes

Primary Outcomes

Results of clinical laboratory research tests

Time Frame: Initial Visit and on an approximately biennial basis

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.