Facilitating Diagnostics and Prognostics of Parkinsonian Syndromes Using Neuroimaging

Related Clinical Trial
Tau Protein and SV2a Imaging in Patients With Tau Protein-related Diseases Building Online Community for Parkinson’s Palliative Care Test-retest Study With [18F]PI-2620 in PSP-RS and NDC Evaluation of the Efficacy of a Two-week EMST on Dysphagia in Parkinsonian Patients Optimization of Morphomer-based Alpha-synuclein PET Tracers Evaluation of [18F]APN-1607 as a PET Biomarker A Phase 2a Study of TPN-101 in Patients With Progressive Supranuclear Palsy (PSP) RT001 in Patients With Progressive Supranuclear Palsy (PSP) PROGRESSIVE SUPRANUCLEAR PALSY Complex Eye Movements in Parkinson’s Disease and Related Movement Disorders tDCS and Speech Therapy for Motor Speech Disorders Caused by FTLD Syndromes: a Feasibility Study Application od Machine Learning Method in Validation of Screening Cognitive Test for Parkinsonisms Subcutaneous Apomorphine in the Treatment of Progressive Supranuclear Palsy and Cortico Basal Degeneration (APOPARKA) Remote Monitoring in Progressive Supranuclear Palsy (PSP) Trial of Parkinson’s And Zoledronic Acid Rho Kinase (ROCK) Inhibitor in Tauopathies – 1 UPenn Observational Research Repository on Neurodegenerative Disease Evaluation of Imaging Characteristics of [18F]PI-2620 PET in AD and PSP Patients Using High and Low Specific Activity Systematic Assessment of Laryngopharyngeal Function in Patients With MSA, PD, and 4repeat Tauopathies The MOTIVE-PSP Initiative A Study to Test the Safety and Tolerability of Long-term UCB0107 Administration in Study Participants With Progressive Supranuclear Palsy Efficacy and Safety of Transcranial dIrect Current stiMulation (tDCS) in Progressive Supranuclear Palsy (PSP) (STIM-PSP) Image Characteristic and Longitudinal Follow up of 18F-PMPBB3 (APN-1607) PET for Progressive Supranuclear Palsy Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of NIO752 in Progressive Supranuclear Palsy Misfolded Proteins in the Skin of People With Parkinson’s Disease and Other Parkinsonism Neurodegenerative Diseases Registry Transcranial Magnetic Stimulation in Progressive Supranuclear Palsy 18F-PM-PBB3 PET Study in Tauopathy Including Alzheimer’s Disease, Other Dementias and Normal Controls Brain Network Activation in Patients With Movement Disorders Neurologic Stem Cell Treatment Study ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) Transcranial Duplex Scanning and Single Photon Emission Computer Tomography (SPECT) in Parkinsonian Syndromes ADDIA Proof-of-Performance Clinical Study Defining Phenotypes of Movement Disorders :Parkinson’s Plus Disorders (PD), Essential Tremor (ET), Cortical Basal Degeneration (CBD), Multiple Systems Atrophy (MSA), Magnetoencephalography. Gait Analysis in Neurological Disease Diagnosing Frontotemporal Lobar Degeneration Evaluation of [18F]MNI-815 as a Potential PET Radioligand for Imaging Tau Protein in the Brain of Patients With Tauopathies Study of the Neural Basis of Analogical Reasoning Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Phase 1 Test-retest Evaluation of [18F]MNI-958 PET Diagnostic and Prognostic Biomarkers in Parkinson Disease Tau Imaging With JNJ067 Research of Biomarkers in Parkinson Disease More Than a Movement Disorder: Applying Palliative Care to Parkinson’s Disease Safety and Efficacy of Droxidopa for Fatigue in Patients With Parkinsonism Identifying Biomarkers of Parkinson’s Disease Using Magnetic Resonance Imaging (MRI) Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) Davunetide (AL-108) in Predicted Tauopathies – Pilot Study Robot Walking Rehabilitation in Parkinson’s Disease Human CNS Tau Kinetics in Tauopathies 4-Repeat Tauopathy Neuroimaging Initiative – Cycle 2 In-Home Care for Patients With PSP and Related Disorders Facilitating Diagnostics and Prognostics of Parkinsonian Syndromes Using Neuroimaging Study of NBMI Treatment in Patients With Atypical Parkinsons (PSP or MSA) Biomarkers in Parkinsonian Syndromes Evaluation of [18F]MNI-952 as a Potential PET Radioligand for Imaging Tau Protein in the Brain Effects of Coenzyme Q10 in PSP and CBD 2-(1-{6-[(2-[F-18]Fluoroethyl) (Methyl)Amino]-2-naphthyl} Ethylidene) Malononitrile-PET for in Vivo Diagnose of Tauopathy in Unclassified Parkinsonism Oxford Study of Quantification in Parkinsonism A Study to Evaluate the Diagnostic Efficacy of DaTSCAN™ Ioflupane (123I) Injection in Single Photon Emission Computed Tomography (SPECT) for the Diagnosis of Parkinsonian Syndrome (PS) in Chinese Patients Evaluation of [18F]MNI-777 PET as a Marker of Tau Pathology in Subjects With Tauopathies Compared to Healthy Subjects The Neural Basis for Frontotemporal Degeneration Analysis of the Enteric Nervous System Using Colonic Biopsies Evaluation of Tolfenamic Acid in Individuals With PSP at 12-Weeks Chromatic Pupillometry to Assess the Melanopsin-Light Pathway in Progressive Supranuclear Palsy 4 Repeat Tauopathy Neuroimaging Initiative A Study to Assess Tolerability, Safety, Pharmacokinetics and Effect of AZP2006 in Patients With PSP Foot Mechanical Stimulation for Treatment of Gait and Gait Related Disorders in Parkinson’s Disease and Progressive Supranuclear Palsy. Safety Study of TPI-287 to Treat CBS and PSP Phase 0 Evaluation of [18F]MNI-958 as a Potential PET Radioligand for Imaging Tau Protein in the Brain Neuroprotection and Natural History in Parkinson’s Plus Syndromes (NNIPPS) Efficacy Study for Treatment of Dementia in Progressive Supranuclear Palsy A 6 Month, Open-Label, Pilot Futility Clinical Trial of Oral Salsalate for Progressive Supranuclear Palsy Pathophysiology of Gait and Posture in Progressive Supranuclear Palsy A Pilot Clinical Trial of Pyruvate, Creatine, and Niacinamide in Progressive Supranuclear Palsy. Clinical Trial to Evaluate Bone Marrow Stem Cell Therapy for PSP, a Rare Form of Parkinsonism tDCS Plus Physical Therapy for Progressive Supranuclear Palsy Repetitive Transcranial Magnetic Stimulation (TMS) for Progressive Supranuclear Palsy and Corticobasal Degeneration Risk Factors for Progressive Supranuclear Palsy (PSP) Continuously Infused Recombinant-Methionyl Human Glial Cell Line-Derived Neurotrophic Factor (GDNF) to Treat Progressive Supranuclear Palsy Cerebellar rTMS Theta Burst for Postural Instability in Progressive Supranuclear Palsy Neuropsychological Evaluation for Early Diagnosis of PSP Evaluating Cerebrospinal Fluid Biomarkers in Alzheimer’s, Progressive Supranuclear Palsy Subjects, and Controls A Pilot Trial of Lithium in Subjects With Progressive Supranuclear Palsy or Corticobasal Degeneration Extension Study of ABBV-8E12 in Patients With Progressive Supranuclear Palsy (PSP) Who Completed Study C2N-8E12-WW-104 Study About Safety and Efficacy of Coenzyme Q10 in Progressive Supranuclear Palsy Study of the Distractibility Syndrome in Patients With Progressive Supranuclear Palsy Tau Imaging in Subjects With Progressive Supranuclear Palsy, Corticobasal Degeneration and Healthy Volunteers Extension Study of BIIB092 in Participants With Progressive Supranuclear Palsy (PSP) Who Participated in CN002003 PROgressive Supranuclear Palsy CorTico-Basal Syndrome Multiple System Atrophy Longitudinal Study UK The Study to Evaluate the Safety and Efficacy of Spinal Cord Stimulation on Progressive Supranuclear Palsy Study to Evaluate the Safety and Efficacy of Davunetide for the Treatment of Progressive Supranuclear Palsy Young Plasma Transfusions for Progressive Supranuclear Palsy Study of BIIB092 in Participants With Progressive Supranuclear Palsy A Study to Test the Safety and Tolerability of UCB0107 in Study Participants With Progressive Supranuclear Palsy (PSP) Safety, Tolerability, and Pharmacokinetics of C2N-8E12 in Subjects With Progressive Supranuclear Palsy Deep TMS for the Treatment of Patients With Parkinson’s Disease and Progressive Supranuclear Palsy Rehabilitation in Patients With Progressive Supranuclear Palsy A Molecular Anatomic Imaging Analysis of Tau in Progressive Supranuclear Palsy Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy Multiple Ascending Dose Study of Intravenously Administered BMS-986168 (BIIB092) in Patients With Progressive Supranuclear Palsy Effects of Coenzyme Q10 in Progressive Supranuclear Palsy (PSP) Quality of Life of the Patient and the Burden of the Caregiver in Progressive Supranuclear Palsy An Extension Study of ABBV-8E12 in Progressive Supranuclear Palsy (PSP) A Study to Assess Efficacy, Safety, Tolerability, and Pharmacokinetics of ABBV-8E12 in Subjects With Progressive Supranuclear Palsy (PSP). Trial of Valproic Acid in Patients With Progressive Supranuclear Palsy (Depakine) Safety, Tolerability, and Efficacy of Two Different Oral Doses of NP031112 Versus Placebo in the Treatment of Patients With Mild-to-Moderate Progressive Supranuclear Palsy Efficacy, Tolerability and Safety of Azilect in Subjects With Progressive Supranuclear Palsy Postural Instability in Progressive Supranuclear Palsy

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

October 2022

Primary Completion Date

August 2022

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, [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

January 2022