Magnetic Resonance Spectroscopy in Autonomic Failure - Full Text View

Purpose

This research study will be conducted in patients with primary autonomic failure, a disabling condition that is associated with low blood pressure upon standing. These patients are also not able to control for changes in their blood pressure due to a loss of cardiovascular reflexes that are mediated within the brain. The purpose of this study is to determine whether magnetic resonance spectroscopy (MRS), a non-invasive imaging technique, can measure levels of chemicals (neurotransmitters) in the dorsal medulla, a brain area important for control of cardiovascular function, in autonomic failure patients. Importantly, this study will determine whether there are differences in brain chemicals between patients with peripheral versus central origins of their autonomic failure. The hypothesis is that the neurotransmitter profile in the medulla will be intact in patients with peripheral autonomic failure compared to those with central impairment. Overall, this study will provide insight into understanding the mechanisms involved in autonomic failure and will determine whether a single session of MRS imaging can improve the ability to make an accurate diagnosis in these patients. This would lessen the need for more extensive and invasive clinical testing.

Condition	Intervention
Pure Autonomic Failure Multiple System Atrophy	Procedure: Magnetic Resonance Spectroscopy Imaging


Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Cross-Sectional
Official Title:	Proton Magnetic Resonance Spectroscopy in Primary Autonomic Failure

Resource links provided by NLM:

Genetics Home Reference related topics: multiple system atrophy

Genetic and Rare Diseases Information Center resources: Multiple System Atrophy Pure Autonomic Failure

U.S. FDA Resources

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

N-Acetylaspartate Levels [ Time Frame: 0.5-1.5 hours ] [ Designated as safety issue: No ]
Differences in levels of N-acetylaspartate in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients using single session imaging.

Secondary Outcome Measures:

Myoinositol Levels [ Time Frame: 0.5-1.5 hours ] [ Designated as safety issue: No ]
Differences in levels of myoinositol in the dorsal medulla pure autonomic failure versus multiple system atrophy patients.
GABA Levels [ Time Frame: 0.5-1.5 hours ] [ Designated as safety issue: No ]
Differences in levels of the neurotransmitter GABA in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.
Creatinine Levels [ Time Frame: 0.5-1.5 Hours ] [ Designated as safety issue: No ]
Differences in levels of creatinine-containing compounds in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.
Choline Levels [ Time Frame: 0.5-1.5 Hours ] [ Designated as safety issue: No ]
Differences in levels of choline-containing compounds in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.
Glutamate Levels [ Time Frame: 0.5-1.5 Hours ] [ Designated as safety issue: No ]
Differences in levels of glutamate in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.


Estimated Enrollment:	26
Study Start Date:	July 2012
Estimated Study Completion Date:	December 2016
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
Pure Autonomic Failure Pure autonomic failure is a type of primary autonomic failure characterized by peripheral autonomic nervous system impairment.	Procedure: Magnetic Resonance Spectroscopy Imaging Proton magnetic resonance spectroscopy [1H-MRS] is an emerging imaging tool that allows for non-invasive assessment of brain neurochemistry in human subjects. This technique allows for in vivo quantification of the concentration of neurotransmitters and metabolites in discrete brain regions through detection of hydrogen nuclei in these molecules. Autonomic failure patients will undergo a single imaging session lasting 30 to 90 minutes (0.5-1.5 hours) in the Vanderbilt Human Imaging Institute. Other Name: MRS
Multiple System Atrophy Multiple system atrophy is a type of primary autonomic failure characterized by central autonomic nervous system impairment.	Procedure: Magnetic Resonance Spectroscopy Imaging Proton magnetic resonance spectroscopy [1H-MRS] is an emerging imaging tool that allows for non-invasive assessment of brain neurochemistry in human subjects. This technique allows for in vivo quantification of the concentration of neurotransmitters and metabolites in discrete brain regions through detection of hydrogen nuclei in these molecules. Autonomic failure patients will undergo a single imaging session lasting 30 to 90 minutes (0.5-1.5 hours) in the Vanderbilt Human Imaging Institute. Other Name: MRS

Groups/Cohorts

Assigned Interventions

Pure Autonomic Failure

Pure autonomic failure is a type of primary autonomic failure characterized by peripheral autonomic nervous system impairment.

Procedure: Magnetic Resonance Spectroscopy Imaging

Proton magnetic resonance spectroscopy [1H-MRS] is an emerging imaging tool that allows for non-invasive assessment of brain neurochemistry in human subjects. This technique allows for in vivo quantification of the concentration of neurotransmitters and metabolites in discrete brain regions through detection of hydrogen nuclei in these molecules. Autonomic failure patients will undergo a single imaging session lasting 30 to 90 minutes (0.5-1.5 hours) in the Vanderbilt Human Imaging Institute.

Other Name: MRS

Multiple System Atrophy

Multiple system atrophy is a type of primary autonomic failure characterized by central autonomic nervous system impairment.

Procedure: Magnetic Resonance Spectroscopy Imaging

Proton magnetic resonance spectroscopy [1H-MRS] is an emerging imaging tool that allows for non-invasive assessment of brain neurochemistry in human subjects. This technique allows for in vivo quantification of the concentration of neurotransmitters and metabolites in discrete brain regions through detection of hydrogen nuclei in these molecules. Autonomic failure patients will undergo a single imaging session lasting 30 to 90 minutes (0.5-1.5 hours) in the Vanderbilt Human Imaging Institute.

Other Name: MRS

Eligibility


Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

Primary autonomic failure patients will be recruited from patients already in the hospital participating in the approved protocol "The Evaluation and Treatment of Autonomic Failure." Prospective participants come from several sources including clinic patients, former patients, referrals from other physicians, and subjects that read about the Autonomic Dysfunction Center on the Vanderbilt website.

Criteria

Inclusion Criteria:

Patients with primary autonomic failure who are already participating in the approved Vanderbilt study "Evaluation and Treatment of Autonomic Failure"
Males and females of all races between 18 and 80 years of age
Able and willing to provide informed consent

Exclusion Criteria:

Pregnant women
Patients with diagnosed Parkinson's Disease or secondary forms of autonomic failure
Patients with severe claustrophobia
Patients taking medications known to affect brain neurotransmitter levels [e.g., anti-depressants, barbiturates, benzodiazepines, gabapentin, namenda, sinemet]
Patients with implanted medical devices [e.g., pacemakers, metal clips, cochlear implants, orthopedic hardware], lead-based tattoos or pieces of metal close to or in an important organ
High-risk patients [e.g., heart failure, symptomatic coronary artery disease, liver impairment, history of stroke or myocardial infarction]
Inability to give or withdraw informed consent
Other factors which in the investigator's opinion would prevent the subject from completing the protocol including significant abnormalities in clinical, mental, or laboratory testing

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01607268

Contacts


Contact: Bonnie K Black, RN	615-343-6862	bonnie.black@Vanderbilt.edu

Locations


United States, Tennessee
Vanderbilt University	Recruiting
Nashville, Tennessee, United States, 37211
Contact: Bonnie Black, RN 615-343-6862 bonnie.black@vanderbilt.edu
Sub-Investigator: Alfredo Gamboa, MD
Sub-Investigator: Amy C Arnold, PhD
Principal Investigator: Italo Biaggioni, MD
Sub-Investigator: Andre Diedrich, MD, PhD
Sub-Investigator: Cyndya Shibao, MD
Sub-Investigator: David Robertson, MD
Sub-Investigator: Emily Garland, PhD
Sub-Investigator: Luis E Okamoto, MD
Sub-Investigator: Satish R Raj, MD

Sponsors and Collaborators

Vanderbilt University

Investigators


Principal Investigator:	Italo Biaggioni, MD	Vanderbilt University

More Information

Additional Information:

Vanderbilt Autonomic Dysfunction Center This link exits the ClinicalTrials.gov site


Responsible Party:	Italo Biaggioni, Professor and Associate Director Clinical Research Center, Vanderbilt University
ClinicalTrials.gov Identifier:	NCT01607268 History of Changes
Other Study ID Numbers:	120574
Study First Received:	May 17, 2012
Last Updated:	July 26, 2016
Health Authority:	United States: Institutional Review Board United States: Food and Drug Administration

Keywords provided by Vanderbilt University:


autonomic failure mangenetic resonance neurochemistry neurotransmitter glutamate

Additional relevant MeSH terms:


Multiple System Atrophy Shy-Drager Syndrome Atrophy Pure Autonomic Failure Pathological Conditions, Anatomical Primary Dysautonomias Autonomic Nervous System Diseases Nervous System Diseases Basal Ganglia Diseases Brain Diseases	Central Nervous System Diseases Movement Disorders Neurodegenerative Diseases Hypotension Vascular Diseases Cardiovascular Diseases Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 23, 2016