Evaluation of Primary Chronic Autonomic Failure
|First Received Date ICMJE||April 16, 2003|
|Last Updated Date||September 19, 2017|
|Start Date ICMJE||April 10, 2003|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||Complete list of historical versions of study NCT00059033 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Evaluation of Primary Chronic Autonomic Failure|
|Official Title ICMJE||Clinical Laboratory Evaluation of Primary Chronic Autonomic Failure|
This study will conduct tests in patients with primary chronic autonomic failure (CAF) to learn more about these disorders, which include pure autonomic failure, multiple system atrophy, Parkinson's disease with autonomic failure, and autoimmune autonomic neuropathy.
Healthy volunteers and patients with primary CAF 18 years of age or older may be eligible for this study. Participants undergo some of the following tests:
In dysautonomias, altered functions of one or more components of the autonomic nervous system adversely affect health. Primary dysautonomias have been classified clinically into chronic autonomic failure (CAF) syndromes that include pure autonomic failure (PAF), multiple system atrophy (MSA), and Parkinson disease (PD) with autonomic failure (manifested especially by neurogenic orthostatic hypotension (OH)). Clinical assessment alone is often inadequate for correct diagnosis and does not provide insights into mechanisms or identify new therapeutic targets. This protocol calls for continuous development and assessment of physiological, neuropharmacologic, neurochemical, neuroimaging, and other clinical laboratory approaches, to identify lesion types and sites in CAF and improve diagnosis, increase mechanistic understanding, and incite novel therapeutics. PAF, MSA, and PD exemplify alpha synucleinopathies, in which deposits of the protein alpha-synuclein occur in Lewy bodies in catecholamine-producing neurons (PD, PAF) or in the cytoplasm of glial cells (MSA). Only the Lewy body forms of synucleinopathy are consistently associated with loss of catecholaminergic neurons. Under this protocol we have obtained evidence that patients with Lewy body diseases have decreased ability to take up intra-neuronal catecholamines from the cytoplasm into storage vesicles. Cytoplasmic catecholamines are cytotoxic, such as by enzyme-catalyzed conversion to highly reactive catecholaldehydes. By studying CAF patients we hope to make discoveries that will yield a unifying, integrative concept for the pathogenesis and different clinical manifestations of Lewy body diseases. Autonomic function testing under this protocol is also required for screening purposes for entry into other protocols of the Clinical Neurocardiology Section. Moreover, comprehensive autonomic function testing is requested in patients of the NIH Undiagnosed Diseases Program. Finally, in a long-term project as a member of the Autonomic Rare Diseases Clinical Research Consortium we are applying this testing to study the natural history of neurogenic OH.
The study population consists of patients with idiopathic, or primary, CAF, with emphasis on PAF, MSA, and PD. Comparison groups include healthy volunteers (HVs), patients with PD who do not have OH, and patients with iatrogenic CAF such as from bilateral thoracic sympathectomies.
Design: Subjects undergo multiple physiological, neuropharmacologic, neurochemical, and neuroimaging, and other tests, to see if the results by different modalities agree and point to specific sites and types of lesions.
Physiological outcome measures include hemodynamic responses to the Valsalva maneuver, orthostasis, and altered temperature at skin of the back. Neuropharmacologic measures include cardiovascular responses to test drugs that probe specific components of the autonomic nervous system. Neurochemical measures include plasma, cerebrospinal fluid, microdialysate, urine, and skin biopsy tissue levels of catecholamines and related compounds. Neuroimaging measures include positron emission tomographic scanning after injection of 18F-dopamine, 18F-DOPA, 13N-ammonia, or 11C-methylreboxetine.
|Study Type ICMJE||Observational|
|Study Design ICMJE||Not Provided|
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Not Provided|
|Study Population||Not Provided|
|Condition ICMJE||Autonomic Nervous System Diseases|
|Intervention ICMJE||Not Provided|
|Study Groups/Cohorts||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Recruiting|
|Estimated Enrollment ICMJE||435|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
The subjects are patients with known or suspected primary CAF, based on referral information and confirmation of the clinical diagnosis at the intake evaluation. They are classified by results of the intake evaluation and then undergo comprehensive autonomic function testing.
Patients with primary or iatrogenic CAF are included. Control patients have been previously diagnosed with PD or MSA without OH, confirmed at the time of the intake evaluation.
Healthy Volunteers 18 years old or older are included. People at increased risk for PD or CAF consent in this study as if they were patients (e.g., to enable DNA extraction and storage).
All subjects must be able to provide their own consent to participate or have an existing Durable Power of Attorney (DPA) in place.
Age: People younger than 18 years old are excluded.
Risk: A candidate subject is excluded if, in the judgment of the Principal Investigator or Clinical Director, protocol participation would place the subject at substantially increased acute medical risk. This includes the risks associated with air travel to the NIH. A candidate subject is excluded if, in the opinion of the Principal Investigator or Clinical Director, the medical risk outweighs the potential scientific benefit.
Disqualifying Conditions A candidate subject is excluded if there is a disqualifying condition. Examples of disqualifying conditions are hepatic or renal failure (defined by serum creatinine more than 1.5 g/dL), symptomatic congestive heart failure, severe anemia, psychosis, refractory ventricular arrhythmias, and symptomatic coronary heart disease. Patients are excluded from further participation if the results of the intake evaluation lead to a diagnosis of a secondary form of CAF, such diabetic autonomic neuropathy. Candidate subjects who are unable to give their own consent and who do not have an existing DPA in place are excluded. Pregnant or lactating women are excluded from the study.
Medications Patients with known or suspected allergy or hypersensitivity to any test drug are excluded from receiving that drug. Patients are not to discontinue any medications before the patient or the patient s doctor discusses this with the Principal Investigator, Research Nurse, or Nurse Practitioner. If it is decided that discontinuing medications would be unsafe, then the patient may be excluded from all or part of the study.
Herbal Medicines and Dietary Supplements Certain herbal medicines or dietary supplements are known or suspected to interfere with the experimental results, and such herbal medicines or dietary supplements may be disallowed before enrollment in the study. For many herbal medicines or dietary supplements, the mechanisms of action and therefore the possible effects on the experimental results are unknown. In cases where the subjects wish to continue their herbal medicines or dietary supplements while on study, and search of the available medical literature fails to identify effects that are known or expected to interfere with the experimental results, then the subjects may participate.
Practical Limitations Patients in whom we feel it would be difficult to insert a catheter into a vein may be excluded. Subjects who are not expected clinically to tolerate lying still during the procedures may be excluded.
Pregnancy Pregnant or lactating women are excluded from the protocol overall. In women with child-bearing potential, blood testing for pregnancy will be done with 24 hours before initial testing (except for obtaining the medical history and physical examination) or any testing involving radioactivity under the protocol. Repeat pregnancy testing will be done before any procedure or drug administration under the protocol that takes place more than one week from a previous pregnancy test. Participants will not start or remain in the study if pregnancy test is positive.
Refusal to Undergo Certain Procedures Candidate subjects are excluded if they refuse to undergo certain procedures. These are: (1) IV catheter; (2) electrocardiogram; (3) blood drawing; (4) DNA extraction and storage (patients and non-HV controls only); and (5) DNA analysis (patients and non-HV controls only).
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||Yes|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00059033|
|Other Study ID Numbers ICMJE||030004
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||National Institute of Neurological Disorders and Stroke (NINDS)|
|Collaborators ICMJE||Not Provided|
|PRS Account||National Institutes of Health Clinical Center (CC)|
|Verification Date||August 3, 2017|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP