PET Imaging Study of Neurochemical and Autonomic Disorders in Multiple System Atrophy (MSA)
| Status: | Completed |
|---|---|
| Conditions: | Other Indications, Neurology |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 30 - 80 |
| Updated: | 11/7/2018 |
| Start Date: | July 2011 |
| End Date: | September 2018 |
Pathogenesis and Diagnosis of Multiple System Atrophy (MSA): PET Study of Neurochemical and Autonomic Disorders in 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:
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.
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.
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.
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.
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
We found this trial at
1
site
Ann Arbor, Michigan 48109
Principal Investigator: Praveen Dayalu, M.D.
Phone: 734-936-8281
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