Magnetic Resonance Spectroscopy in Autonomic Failure

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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 or disease	Intervention/treatment
Pure Autonomic Failure; Multiple System Atrophy	Procedure: Magnetic Resonance Spectroscopy Imaging

Study Design

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Study Type :	Observational
Actual Enrollment :	6 participants
Observational Model:	Case Control
Time Perspective:	Cross-Sectional
Official Title:	Proton Magnetic Resonance Spectroscopy in Primary Autonomic Failure
Study Start Date :	July 2012
Actual Primary Completion Date :	January 2017
Actual Study Completion Date :	January 2017

Groups and Cohorts

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort	Intervention/treatment
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

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. N-Acetylaspartate Levels [ Time Frame: 0.5-1.5 hours ]
   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 :

1. Myoinositol Levels [ Time Frame: 0.5-1.5 hours ]
   Differences in levels of myoinositol in the dorsal medulla pure autonomic failure versus multiple system atrophy patients.
2. GABA Levels [ Time Frame: 0.5-1.5 hours ]
   Differences in levels of the neurotransmitter GABA in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.
3. Creatinine Levels [ Time Frame: 0.5-1.5 Hours ]
   Differences in levels of creatinine-containing compounds in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.
4. Choline Levels [ Time Frame: 0.5-1.5 Hours ]
   Differences in levels of choline-containing compounds in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.
5. Glutamate Levels [ Time Frame: 0.5-1.5 Hours ]
   Differences in levels of glutamate in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
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

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37211

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:	Italo Biaggioni, MD	Vanderbilt University

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Vanderbilt Autonomic Dysfunction Center 

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
First Posted:	May 30, 2012
Last Update Posted:	January 18, 2017
Last Verified:	January 2017

Keywords provided by Italo Biaggioni, Vanderbilt University:

autonomic failure; mangenetic resonance; neurochemistry; neurotransmitter; glutamate

Additional relevant MeSH terms:

Atrophy; Multiple System Atrophy; Shy-Drager Syndrome; 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