Longitudinal Tracking of Patients Diagnosed With Neurodegenerative Movement Disorders

The purpose of this protocol is to create an active natural history cohort of patients with degenerative movement disorders, tracked in a clinical setting with clinical rating scales and neuroimaging. The overarching rationale is that neurodegenerative diseases may be heterogeneous, complex disorders. A new way of performing clinical trials in these patients may be in order and this protocol aims to build a longitudinally tracked clinical trial-ready cohort of patients. The purpose of this protocol is to establish an active natural history cohort of patients with neurodegenerative movement disorders who are deeply phenotyped and "clinical trial ready" across Mass General Brigham.

After a thorough clinical diagnostic evaluation (this may include clinically indicated testing, for example MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, inflammatory tests, skin biopsy) the investigators aim to achieve this through:

1. Longitudinal tracking of clinical progression through use of clinical scales including at the present time: UMSARS, BARS, MoCA and UPSIT, PROM, MDS-NMS, UPDRS, and SARA
2. Longitudinal tracking of disease progression through use of neuroimaging including at the present time: TSPO-PET and 3D MRI (see section 1.3)

This is a pilot study designed to track patients with neurodegenerative movement disorders across Mass General Brigham through MRI and PET imaging modalities and clinical measures. Figure 5 represents the study design in detail. In short, subjects will be asked to visit Mass General Brigham every 6-9 months over the course of 18 months for imaging and clinical evaluation.

Study Overview

• Status: Recruiting
• Conditions: Synucleinopathies; Neurodegenerative Diseases; Ataxia; sca3; MSA - Multiple System Atrophy
• Intervention / Treatment: Drug: 18F-PBR06; Radiation: 18F-PBR06

Detailed Description

After a thorough clinical diagnostic evaluation (this may include clinically indicated testing, for example MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, inflammatory tests, skin biopsy) the investigators aim to achieve this through:

1. Longitudinal tracking of clinical progression through use of clinical scales including at the present time: UMSARS, BARS, MoCA and UPSIT, PROM, MDS-NMS, UPDRS, and SARA
2. Longitudinal tracking of disease progression through use of neuroimaging including at the present time: TSPO-PET and 3D MRI (see section 1.3)

This is a pilot study designed to track patients with neurodegenerative movement disorders across Mass General Brigham through MRI and PET imaging modalities and clinical measures. Figure 5 represents the study design in detail. In short, subjects will be asked to visit Mass General Brigham every 6-9 months over the course of 18 months for imaging and clinical evaluation.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Vikram Khurana, MD PhD; Email: vkhurana@bwh.harvard.edu
• Study Contact Backup: Name: Diego Rodriguez, MD; Phone Number: 507-491-0272; Email: drodriguez29@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Diego Rodriguez, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

individuals with a clinical diagnosis of neurodegenerative movement disorder by consensus criteria (MSA, ataxias, synuclein duplication, atypical parkinsonism, etc)

Description

Inclusion Criteria:

1. Clinical diagnosis of neurodegenerative movement disorder by consensus criteria including: MSA, ataxias, synuclein duplication, atypical parkinsonism
2. Male and female subjects aged 18 and up

Exclusion Criteria:

1. Individuals with a known alternate neurologic disorder including: idiopathic PD, DLB, PSP, ALS, Alzheimer's, prion disease, frontotemporal dementia, seizure disorder, stroke, or brain tumor
2. Individuals with a previous head injury (with 15 minutes or greater loss of consciousness within the past 20 years)
3. Individuals with substance abuse, or substance abuse disorder
4. Brain MRI indicative of a significant abnormality (i.e. prior hemorrhage or infarct greater than 1 cm3, 3 or more lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space- occupying lesion).
5. Individuals with bipolar disease and schizophrenia
6. Concurrent medical conditions that contraindicate study procedures
7. Women who are pregnant, nursing, or seeking to become pregnant
8. Individuals with claustrophobia
9. Non-MRI compatible implanted devices
10. Corticosteroid treatment in the past four weeks
11. Low affinity binders to TSPO
12. Significant cognitive impairment (MoCA score ≤ 23) or poor understanding of study design

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
participants; all participants in this study must have a diagnosis of a neurodegenerative movement disorder	Drug: 18F-PBR06; TSPO-PET (translocatior protein, positron emission tomography) scan; Radiation: 18F-PBR06; TSPO-PET (translocatior protein, positron emission tomography) scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
association between change in PET and clinical measures	For the longitudinal evaluation, the investigators will estimate the association between the change in the PET and the change in the clinical and morphometric outcome measures using a mixed model with both the baseline PET uptake and the rate of change in PET uptake as predictors. This approach will allow the investigators to estimate both how between and within subject changes in PET impact the outcomes of interest. The investigators will use a p<0.05, corrected for multiple comparisons.	18 months

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Vikram Khurana, MD PhD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Anticipated): September 15, 2024
• Study Completion (Anticipated): November 15, 2024

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 22, 2023
• Last Update Submitted That Met QC Criteria: May 19, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Proteostasis Deficiencies; Autonomic Nervous System Diseases; Primary Dysautonomias; Hypotension; Neurodegenerative Diseases; Movement Disorders; Multiple System Atrophy; Shy-Drager Syndrome; Synucleinopathies
• Other Study ID Numbers: 2022P001295

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No