PET Imaging Study of Neurochemical and Autonomic Disorders in Multiple System Atrophy (MSA)
Multiple system atrophy (MSA) is a disorder of the nervous system of unclear cause. In MSA there is degeneration (progressive loss) of nerve cells in several brain and spinal cord regions. The result is a variety of symptoms, from physical (parkinsonism, ataxia, incoordination, falls, slowness) to autonomic (fainting, bladder incontinence, sexual dysfunction) to sleep problems (dream enactment, sleep apnea).
This research aims to help us better understand the patterns and timing of nerve degeneration relatively early in the disease, and how this affects symptoms and progression. For instance:
- Does MSA affect certain nerves that stimulate heart pumping? If so, does the severity of loss of heart nerves affect disease progression and survival?
- It is thought that MSA does not affect memory and thinking much, unlike other diseases (such as Parkinson's). Is this accurate? Is there loss of nerves that transmit acetylcholine (a neurochemical important in mental functioning)?
- What can we learn about mood and sleep in MSA, through visualizing the serotonin system in the brain? How does this relate to symptoms that subjects report in these often underappreciated areas?
To answer these and other questions, investigators will take images of specific nerves in the brain and heart using Positron Emission Tomography (PET) scans. Such imaging gives us information that cannot be obtained from MRIs and CT scans. We will measure the levels of several nerve cell types: serotonin, acetylcholine, and norepinephrine. Subjects will also have many standardized assessments including quality-of-life and symptom assessments, neurological examination, autonomic assessments, neuropsychological assessments, coordination tests, and even assessments of vision and sense of smell. By pooling these results from many MSA patients, and comparing with other diseases (such as Parkinson's disease) we hope to gain a better understanding of what is happening early in MSA. Such knowledge could be very valuable in future efforts to develop better therapies in this rare disease.
Multiple System Atrophy - Parkinsonian Subtype (MSA-P)
Multiple System Atrophy - Cerebellar Subtype (MSA-C)
|Study Design:||Observational Model: Case-Only
Time Perspective: Cross-Sectional
|Official Title:||Pathogenesis and Diagnosis of Multiple System Atrophy (MSA): PET Study of Neurochemical and Autonomic Disorders in MSA|
- Cardiac denervation [ Time Frame: 1 time ] [ Designated as safety issue: No ]Early MSA patients vary in their degree of cardiac denervation. A greater degree of cardiac denervation is associated with greater baseline impairment of autonomic, visual and olfactory functions, and predicts a more rapid decline of these functions as well as motor performance.
- MSA Rate of Progression [ Time Frame: 1 time ] [ Designated as safety issue: No ]To determine whether MSA subjects differ in progression rates based upon the relative timing of autonomic failure, particularly cardiac denervation.
Biospecimen Retention: Samples With DNA
DNA Banking (this is optional): Subjects will have whole blood drawn sample for DNA banking to support genetic research of human disease and human genetic factors. About two tablespoons (approximately 20 ml) of blood will be taken from you. The blood will be shipped to the laboratory of Dr. Philip Low, Mayo Clinic, MN. Dr. Low's laboratory will extract the DNA. Members of the North American MSA - Study Group and their collaborators will use the DNA to try to find out if changes in certain genes are associated with MSA. The samples will be used for the preparation of DNA, and possibly, an immortalized cell line. The cell line, DNA, and accompanying data will be distributed to scientists including those in research, teaching, and industry. The samples may be kept indefinitely. The samples and accompanying information will be used for studying of many disorders and genetic factors, not just MSA.
|Study Start Date:||July 2011|
|Estimated Study Completion Date:||September 2016|
|Estimated Primary Completion Date:||July 2016 (Final data collection date for primary outcome measure)|
The screening evaluation will take less than 1 to 2 hours, and is usually conducted over the telephone. The visit for testing will take approximately 3 days, consisting (usually) of a day for clinical examinations and questionnaires and one day each for PET and MRI brain imaging and the third day for PET imaging of the heart and autonomic testing. If some checklists and questionnaires could not be completed conveniently in the time available, they may be finished over the telephone on a later day. At the completion of the 3-day evaluation, subjects are asked to return home and keep a log of their MSA symptoms and medication responses for 2 days. This will complete the active participation of MSA subjects in all aspects of the entire research program. The average time the subjects will be followed could be up to 1 week during which time the subjects are undergoing research related procedures.
Positron Emission Tomography (PET) imaging involves injection of radioactive tracers (small amounts of biologically active molecules with radioactive atoms attached) and scanning the body to see where the tracers localize, and how intensely they "stick" there.
The tracers are used in such small amounts that they do not affect brain or body functions. The amount of radioactivity used is also very small and disappears quickly. Overall radiation exposure for participants is low and well within accepted safety levels for the human body.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02035761
|Contact: Arijit K Bhaumik, B.A., CCRPfirstname.lastname@example.org|
|Contact: Edna Rose, Ph.D., RN, MSW, BCemail@example.com|
|United States, Michigan|
|University of Michigan - Department of Neurology||Recruiting|
|Ann Arbor, Michigan, United States, 48109|
|Contact: Arijit K Bhaumik, B.A. 734-936-8281 firstname.lastname@example.org|
|Contact: Stephen Campbell, LLMSW 734-763-2361 email@example.com|
|Principal Investigator: Praveen Dayalu, M.D.|
|Principal Investigator:||Praveen Dayalu, M.D.||University of Michigan|