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PET Imaging Study of Neurochemical and Autonomic Disorders in Multiple System Atrophy (MSA)

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ClinicalTrials.gov Identifier: NCT02035761
Recruitment Status : Completed
First Posted : January 14, 2014
Last Update Posted : November 5, 2018
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Praveen Dayalu, MD, University of Michigan

Tracking Information
First Submitted Date January 10, 2014
First Posted Date January 14, 2014
Last Update Posted Date November 5, 2018
Study Start Date July 2011
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 13, 2014)
Cardiac denervation [ Time Frame: 1 time ]
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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: January 13, 2014)
MSA Rate of Progression [ Time Frame: 1 time ]
To determine whether MSA subjects differ in progression rates based upon the relative timing of autonomic failure, particularly cardiac denervation.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title PET Imaging Study of Neurochemical and Autonomic Disorders in Multiple System Atrophy (MSA)
Official Title Pathogenesis and Diagnosis of Multiple System Atrophy (MSA): PET Study of Neurochemical and Autonomic Disorders in MSA
Brief Summary

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:

  1. Does MSA affect certain nerves that stimulate heart pumping? If so, does the severity of loss of heart nerves affect disease progression and survival?
  2. 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)?
  3. 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.

Detailed Description

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.

Study Type Observational
Study Design Observational Model: Case-Only
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
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.
Sampling Method Non-Probability Sample
Study Population Possible or Probable Multiple System Atrophy of either Parkinsonian or Cerebellar sub-type
  • Multiple System Atrophy - Parkinsonian Subtype (MSA-P)
  • Multiple System Atrophy - Cerebellar Subtype (MSA-C)
Intervention Not Provided
Study Groups/Cohorts MSA Case
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.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: November 2, 2018)
Original Estimated Enrollment
 (submitted: January 13, 2014)
Actual Study Completion Date September 2018
Actual Primary Completion Date September 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

Participants aged 30-80 years old with a diagnosis of Possible or Probable MSA of the parkinsonian subtype (MSA-P) or cerebellar subtype (MSA-C)

Participants who are less than 4 years from the time of documented MSA diagnosis

Participants who are willing and able to give informed consent

"Normal" cognition as assessed by Mini Mental State Examination

Exclusion Criteria:

Pregnant or lactating females

Participants with a clinically significant or unstable medical or surgical condition that, in the opinion of the investigator, might preclude safe completion of the study or might affect the results of the study. These include conditions causing significant CNS or autonomic dysfunction, including congestive heart failure, recent (<6 months) myocardial infarction, thrombocytopenia (<50 x 10(9)/L), immunosuppressed state, severe uncontrolled hypertension, severe cardiopulmonary disease, severe anemia (hemoglobin <8g/dl), severe liver or kidney disease (creatinine >2.3 mg/dl) uncontrolled diabetes mellitus (HbA1c >10g%), alcoholism, malignant neoplasms, amyloidosis, uncontrolled hypothyroidism, unstable peripheral neuropathies, concurrent infections, orthopedic problems that compromise mobility and activities of daily living, severe cerebrovascular accidents (causing symptoms such as hemiplegia, aphasia and non-dominant parietal lobe syndrome), and neurotoxins or neuroactive drug exposure, parkinsonism due to drugs (including neuroleptics, L-methyldopa, reserpine, metoclopramide).

Females who are pregnant

Subjects known to have porphyria

The regular use of neuroleptics within the six months prior to the initial evaluation. Occasional use of a neuroleptic as an anti-emetic in the past is allowed, providing not more than three doses were taken within the previous 12 months

Diseases more consistent with Lewy Body dementia, progressive supranuclear palsy, essential tremor, inherited cerebellar degeneration, or postencephalitic parkinsonism

Subjects receiving psychostimulants, antimuscarinics (trihexphenidyl, benztropine, and tricyclic antidepressants), acetylcholinesterase inhibitors, trazodone or modafinil will be excluded as they may interfere with study measures. Subjects with prior exposure to disallowed medications may be eligible if there has been an interval of > 2months for these medications, at the discretion of the investigators

Dementia (DSM-IV criteria - Amer. Psych. Association, 1994). The score on the Mini-Mental State Examination must be >24

Sexes Eligible for Study: All
Ages 30 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
Administrative Information
NCT Number NCT02035761
Other Study ID Numbers NS044233
NS044233 ( Other Grant/Funding Number: NINDS )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Current Responsible Party Praveen Dayalu, MD, University of Michigan
Original Responsible Party Dr. Praveen Dayalu, University of Michigan, Assistant Professor of Neurology
Current Study Sponsor University of Michigan
Original Study Sponsor Same as current
Collaborators National Institute of Neurological Disorders and Stroke (NINDS)
Principal Investigator: Praveen Dayalu, M.D. University of Michigan
PRS Account University of Michigan
Verification Date November 2018