Brief Title
Facilitating Diagnostics and Prognostics of Parkinsonian Syndromes Using Neuroimaging
Official Title
Quantitative Diagnostics of Parkinsonian Syndromes Using Multi-modal Neuroimaging and Deep Learning
Brief Summary
The goals of this study are: 1) to identify biomarkers using neuroimaging that are associated
with progression rate using statistical methods, and 2) to identify biomarkers that are
associated with the differential diagnosis of Parkinson's disease and atypical parkinsonism.
Detailed Description
Management of patients with parkinsonian symptoms has two critical gaps: (1) there are no
clinically accepted biomarkers that may be used to inform disease progression rate in an
individual with Parkinson disease (PD), and (2) no biomarkers exist to inform differential
diagnosis of conditions that exhibit parkinsonian symptoms and signs. This 2-year study aims
to develop a multi-modal neuroimaging biomarker that enables the prediction of disease
progression rate in PD, and a biomarker that enables the differential diagnosis of PD,
multiple systems atrophy (MSA), progressive supranuclear palsy (PSP), and healthy controls.
This study consists of two parts; neuroimaging of a defined population of mid to late stage
PD subjects currently followed at UT Southwestern Medical Center, and recruitment of new
subjects with PD, MSA, and PSP who will be followed clinically over 2 years and who will
undergo neuroimaging.
Participants will be asked to undergo several types of neuroimaging which will be analyzed
using machine learning techniques.
At each study visit of the newly recruited cohorts, appropriate clinical scales will be
performed based on their diagnosis and used to track and measure disease severity and
progression.
Study Type
Observational
Primary Outcome
Imaging biomarker of progression rate
Secondary Outcome
Change from baseline in MDS-UPDRS score
Condition
Parkinson Disease
Study Arms / Comparison Groups
Aim 1: Develop a biomarker of PD disease progression rate
Description: For Aim 1, we will enroll PD subjects spanning a range of progression rates that have been tracked at UT Southwestern Medical Center. Multimodal neuroimaging will be acquired from each subject. We will evaluate imaging data and known data on clinical progression using statistical techniques to determine a biomarker that associates with progression rate.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
90
Start Date
March 28, 2019
Completion Date
August 2024
Primary Completion Date
August 2024
Eligibility Criteria
Inclusion Criteria:
For Aim 1:
- Diagnosis of Parkinson disease
- Existence of sufficient clinical data from previous UTS Southwestern longitudinal study
to determine progression rate (categorized as fast or slow)
- Availability of suitable matched participant in the alternate progression group (fast
or slow)
- Willingness to participate in the imaging studies required for this study and to
provide written informed consent
For Aim 2:
PD subjects will be recruited in accordance with the MDS Clinical Diagnostic Criteria for
PD.
- Duration of PD (since diagnosis) is < 5 years
- Willing to participate in imaging and clinical scoring visits, and provide written
informed consent
- Subject and investigator agree that it is highly likely subject will be able to
participate throughout the 2-year study period (no plans to move)
MSA subjects will be recruited in accordance with the Second Consensus Statement on
Diagnosis of Multiple System Atrophy.
- Duration of MSA (since diagnosis) is < 5 years
- Willing to participate in imaging and clinical scoring visits, and provide written
informed consent
- Subject and investigator agree that it is highly likely subject will be able to
participate throughout the 2-year study period (no plans to move away during the
study)
PSP subjects will be recruited in accordance with the MDS Criteria for Diagnosis of
Progressive Supranuclear Palsy and must meet the designation of "probable PSP" for
inclusion.
- Willing to participate in imaging and clinical scoring visits, and provide written
informed consent
- Subject and investigator agree that it is highly likely subject will be able to
participate throughout the 2-year study period (no plans to move away during the
study)
Control subjects will be recruited who meet the following criteria:
- Roughly age and sex matched with the subjects in the PD cohort
- No history or examination findings suggestive of any neurodegenerative disease
- Normal gait, balance, and eye movements for age
- No clinical evidence for symptomatic orthostatic hypotension
- Willing to participate in imaging and clinical scoring visits, and provide written
informed consent
- Subject and investigator agree that it is highly likely subject will be able to
participate throughout the 2-year study period (no plans to move away during the
study)
Exclusion Criteria:
For Aims 1 and 2:
- Any contraindications to undergoing the multimodal imaging program
- All females of child-bearing potential, between the ages of 18-55, will be excluded
from the study, unless they are confirmed to be not pregnant with a pregnancy test
prior to scanning
- This study will require constant clear communication throughout the duration of the
study; therefore, non-English speakers will be excluded
- Right-handed finger amputees
- Cast on right hand or fingers at the time of enrollment
- Has clinically significant liver, kidney, lung, metabolic or hormone disturbances
which pose safety risk
- Has a current clinically significant heart disease that poses a safety risk
- Has a current clinically significant infectious disease or a medical comorbidity which
poses a safety risk
- Has a history of relevant severe drug allergy or hypersensitivity
- Have a history of drug, alcohol, or substance dependence or abuse within the last
year, or prior prolonged history of dependence or abuse
- Currently undergoing chemotherapy or radiation for cancer
- Recreational drug use in past six months
- Central nervous systems disease or brain injury that would preclude participation in
this study
- Psychiatric or neurological disorder that would preclude participation in this study
- Inability to keep or maintain research appointments
For Aim 1:
- Severe disease progression such that participation in the imaging tests would be
impossible or difficult
- Non-availability of a suitable matched participant in the alternate progression group
(fast or slow)
For Aim 2:
PD subjects
1. Unequivocal cerebellar abnormalities
2. Downward vertical gaze limitation or slowing of downward saccades
3. Diagnosis of behavioral variant frontotemporal dementia or primary progressive aphasia
4. Parkinsonian features restricted to the lower limbs for > 3 years
5. Treatment with dopamine blockers or depleters in a time course consistent with drug
induced parkinsonism
6. Absence of an observable response to high dose levodopa despite moderate disease
severity
7. Expert considers a diagnosis of alternative syndrome more likely than PD
8. Rapid progression of gait impairment requiring wheelchair within 5 years of onset
9. Complete absence of progression of motor symptoms over 5 years unless due to treatment
10. Early bulbar dysfunction within the first 5 years since diagnosis
11. Inspiratory respiratory dysfunction (stridor or frequent sighs)
12. Severe autonomic failure in the first 5 years
13. Recurrent falls (>1 per year) because of impaired balance in the first 3 years
14. Disproportionate dystonic anterocollis or hand contractures of hands or feet within 10
years
15. Absence of any of the common non-motor features of PD despite 5 years of disease
16. Otherwise unexplained pyramidal tract signs (weakness, hyperreflexia, or extensor toe
signs)
17. Bilateral symmetric parkinsonism
MSA subjects
1. Clinically significant neuropathy
2. Hallucinations not induced by drugs
3. Onset after age 75 years
4. Family history of ataxia or parkinsonism
5. White matter lesions suggesting multiple sclerosis
PSP subjects
1. Predominant, otherwise unexplained impairment of episodic memory, suggestive of AD
(Alzheimer's disease)
2. Predominant, otherwise unexplained autonomic failure, e.g., orthostatic hypotension
(orthostatic reduction in blood pressure after 3 minutes standing > 30 mm Hg systolic
or > 15 mm Hg diastolic), suggestive of multiple system atrophy or Lewy body disease
3. Predominant, otherwise unexplained visual hallucinations or fluctuations in alertness,
suggestive of dementia with Lewy bodies
4. Predominant, otherwise unexplained multisegmental upper and lower motor neuron signs,
suggestive of motor neuron disease (pure upper motor neuron signs are not an exclusion
criterion)
5. Sudden onset or step-wise or rapid progression of symptoms, in conjunction with
corresponding imaging or laboratory findings, suggestive of vascular etiology,
autoimmune encephalitis, metabolic encephalopathies, or prion disease
6. History of encephalitis
7. Prominent appendicular ataxia
8. Identifiable cause of postural instability, e.g., primary sensory deficit, vestibular
dysfunction, severe spasticity, or lower motor neuron syndrome
Control subjects
a. In the investigator's opinion, an unsuitable candidate to serve as a control
Gender
All
Ages
N/A - N/A
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Richard B Dewey, MD, 214-648-7578, pheba[email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03872102
Organization ID
Bioinformatics Study
Responsible Party
Principal Investigator
Study Sponsor
University of Texas Southwestern Medical Center
Study Sponsor
Richard B Dewey, MD, Principal Investigator, UT Southwestern Medical Center
Verification Date
September 2022