Magnetic Resonance Spectroscopy in Autonomic Failure

Proton Magnetic Resonance Spectroscopy in Primary Autonomic Failure

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.

Study Overview

• Status: Terminated
• Conditions: Multiple System Atrophy; Pure Autonomic Failure
• Intervention / Treatment: Procedure: Magnetic Resonance Spectroscopy Imaging

• Study Type: Observational
• Enrollment (Actual): 6

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

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 Names: 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 Names: MRS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
N-Acetylaspartate Levels	Differences in levels of N-acetylaspartate in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients using single session imaging.	0.5-1.5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myoinositol Levels	Differences in levels of myoinositol in the dorsal medulla pure autonomic failure versus multiple system atrophy patients.	0.5-1.5 hours
GABA Levels	Differences in levels of the neurotransmitter GABA in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.	0.5-1.5 hours
Creatinine Levels	Differences in levels of creatinine-containing compounds in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.	0.5-1.5 Hours
Choline Levels	Differences in levels of choline-containing compounds in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.	0.5-1.5 Hours
Glutamate Levels	Differences in levels of glutamate in the dorsal medulla of pure autonomic failure versus multiple system atrophy patients.	0.5-1.5 Hours

Collaborators and Investigators

• Sponsor: Vanderbilt University

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: May 17, 2012
• First Submitted That Met QC Criteria: May 24, 2012
• First Posted (Estimate): May 30, 2012

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: January 16, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: autonomic failure; glutamate; neurotransmitter; neurochemistry; mangenetic resonance
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Multiple System Atrophy; Shy-Drager Syndrome; Pure Autonomic Failure
• Other Study ID Numbers: 120574