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

NCT02035761 | Completed

• 1 other identifier: NS044233
• Study Type: observational
• Target: 23
• Locations: 1 country
• Sites: 1

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. 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. 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. 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?

Conditions

Multiple System Atrophy - Parkinsonian Subtype (MSA-P); Multiple System Atrophy - Cerebellar Subtype (MSA-C)

Keywords

MSA; Shy-Dragers Syndrome; Possible or Probable

Outcome Measures

Primary Outcomes (1)

• Cardiac denervation

  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.

  1 time

Secondary Outcomes (1)

• MSA Rate of Progression

  1 time

Study Arms (1)

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.

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Possible or Probable Multiple System Atrophy of either Parkinsonian or Cerebellar sub-type

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Michigan: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

University of Michigan - Department of Neurology

Ann Arbor, Michigan, 48109, United States

Location

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.

MeSH Terms

Conditions

Shy-Drager Syndrome

Condition Hierarchy (Ancestors)

Multiple System Atrophy; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Hypotension; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Praveen Dayalu, M.D.

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Study Record Dates

• First Submitted: January 10, 2014
• First Posted: January 14, 2014
• Study Start: July 1, 2011
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: November 5, 2018

Record last verified: 2018-11

Locations

US (1)