Ignite Creation Date:
2024-05-05 @ 11:29 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00059033
Status:
TERMINATED
Last Update Posted:
2019-12-12
First Post:
2003-04-16
Brief Title:
Evaluation of Primary Chronic Autonomic Failure
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Clinical Laboratory Evaluation of Primary Chronic Autonomic Failure
Status:
TERMINATED
Status Verified Date:
2018-10-30
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 Parkinsons 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
Blood studies including arterial catheter insertion to measure blood pressure and collect arterial blood samples blood flow studies using sensors applied to the skin and a pressure cuff around a limb and blood draw for genetic studies
Bladder motility Ultrasound test of bladder function
Electrocardiogram and heart ultrasound
Responses to changes in temperature Warm water and then room temperature water are passed through watertight pads applied to the back and front of the body and body temperatures are measured
Gastrointestinal motility Bowel sounds are recorded using a microphone placed on the abdomen
Lower body negative pressure The lower body is placed into an airtight barrel-like chamber Some air is sucked out of the barrel causing blood to pool in the legs as occurs during standing
Lumbar puncture A needle is inserted in the space between the bones in the lower back to collect a small sample of cerebrospinal fluid
Microdialysis to measures levels of chemicals in the body fluid of certain tissues A solution is passed through a thin tube inserted into the skin Chemicals in the body tissues enter the solution The solution is collected and the chemical levels are measured
PET scanning A nuclear medicine test to produce images of body organs For patients with urinary problems a catheter is inserted into the bladder before starting the scan
Pupillometry The pupil of the eye is measured using a special camera in a light-controlled room
QSART A small amount of a brain chemical is applied to the skin with a tiny amount of electricity and the sweat in a nearby patch of skin is measured
Measurement of saliva production using a cotton-like material placed between the teeth and gums to absorb saliva
Skin electrical conduction test using sensors on the skin to measure sweat production
Skin and core temperature measurements using sensors on the skin and in the ear canal
Speech and swallowing assessment for patients with speech and swallowing difficulties
Stress echocardiogram A catheter is placed in the subjects arm for sampling blood or giving a drug while the subject exercises During the test blood pressure pulse rate and EKG are continuously monitored
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
Blood studies including arterial catheter insertion to measure blood pressure and collect arterial blood samples blood flow studies using sensors applied to the skin and a pressure cuff around a limb and blood draw for genetic studies
Bladder motility Ultrasound test of bladder function
Electrocardiogram and heart ultrasound
Responses to changes in temperature Warm water and then room temperature water are passed through watertight pads applied to the back and front of the body and body temperatures are measured
Gastrointestinal motility Bowel sounds are recorded using a microphone placed on the abdomen
Lower body negative pressure The lower body is placed into an airtight barrel-like chamber Some air is sucked out of the barrel causing blood to pool in the legs as occurs during standing
Lumbar puncture A needle is inserted in the space between the bones in the lower back to collect a small sample of cerebrospinal fluid
Microdialysis to measures levels of chemicals in the body fluid of certain tissues A solution is passed through a thin tube inserted into the skin Chemicals in the body tissues enter the solution The solution is collected and the chemical levels are measured
PET scanning A nuclear medicine test to produce images of body organs For patients with urinary problems a catheter is inserted into the bladder before starting the scan
Pupillometry The pupil of the eye is measured using a special camera in a light-controlled room
QSART A small amount of a brain chemical is applied to the skin with a tiny amount of electricity and the sweat in a nearby patch of skin is measured
Measurement of saliva production using a cotton-like material placed between the teeth and gums to absorb saliva
Skin electrical conduction test using sensors on the skin to measure sweat production
Skin and core temperature measurements using sensors on the skin and in the ear canal
Speech and swallowing assessment for patients with speech and swallowing difficulties
Stress echocardiogram A catheter is placed in the subjects arm for sampling blood or giving a drug while the subject exercises During the test blood pressure pulse rate and EKG are continuously monitored
Detailed Description:
Objective
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
Study Population
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
Outcome Measures
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
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
Study Population
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
Outcome Measures
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 03-N-0004 | None | None | None |