Multimodal Imaging Outcome Measures for ALS (Image ALS)
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- University of Pennsylvania
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Volume measurement (cubic mm) of brain regions using MRI
Study Overview
Brief Summary
The primary aim of this study is to determine whether longitudinal neuroimaging acquired across multiple research and clinical centers is a feasible biomarker to use as an outcome measure for clinical trials in amyotrophic lateral sclerosis (ALS)
Detailed Description
ALS is a progressive neurodegenerative disorder that manifests with extensive clinical heterogeneity, including variable degrees of upper motor neuron (UMN) and lower motor neuron (LMN) impairment. While ALS is classically defined as a neuromuscular disorder, approximately 15% of individuals also develop cognitive and/or behavioral dysfunction of the frontotemporal variety, ranging in severity from ALS with cognitive or behavior impairment to a frank form of dementia consistent with FTD2
- Recent consensus criteria capture this heterogeneity by defining these conditions together as amyotrophic lateral sclerosis frontotemporal spectrum disorder (ALS-FTSD)3
- There are emerging and in-progress interventional clinical trials underway that aim to arrest ALS and/or FTD disease progression; however, there are limited objective and quantitative biomarkers to directly track disease progression during life. Multi-modal neuroimaging provides an ideal candidate biomarker for clinical trials because ALS-FTSD affects a distributed neuroanatomic network and we can reliably measure neurodegeneration of grey matter (GM) and arterial spin labeling based perfusion MRI (pMRI) measurements of cerebral blood flow (CBF). However, there are many unaddressed technical challenges associated with measuring disease progression using neuroimaging techniques in a multi-center setting. The overall aim of this protocol is to leverage a team science approach to develop disease-specific candidate neuroimaging outcome measures for ALS-FTSD clinical trials.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
[11C]-PBR28 ALS
Neuroinflammatory pathways have been implicated in a variety of neurodegenerative disorders including amyotrophic lateral sclerosis (ALS), but the vast majority of this evidence is from animal or ex vivo human studies. In vivo measurement of the 18 kDa translocator protein (TSPO) has become possible with [11C]-PBR28 PET imaging. Briefly, TSPO expression is increased when microglial are activated. Cross-sectional studies have demonstrated that [11C]-PBR28 uptake is elevated in ALS compared to controls, is correlated with upper motor neuron severity, and that microglial activation is associated with more severe upper motor neuron disease and faster disease progression. We are only aware of a single 6-month study of 10 patients evaluating longitudinal change of [11C]-PBR28 in ALS. We hypothesize that we will observe increased [11C]-PBR28 uptake over a 6-month period in motor cortex and prefrontal cortex in ALS. This portion of the study will be performed at UPenn only.
Intervention: [11C]-PBR28 (Drug)
Outcomes
Primary Outcomes
Volume measurement (cubic mm) of brain regions using MRI
Time Frame: Change from baseline volume measurement (cubic mm) at 12 months
Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.
Thickness measurement (mm) of brain regions using MRI
Time Frame: Change from baseline thickness measurement (mm) at 12 months
Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.
Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI
Time Frame: Change from baseline cerebral blood flow measurement (mL of blood/100g per minute at 12 months
Determine whether MRI is a feasible for measuring longitudinal change comparing ALS patients relative to healthy controls. ALS will have increased rate of hyperperfusion, reflected by reduced cerebral blood flow (mL of blood/100g per minute), in the motor cortex and frontal cortex brain regions relative to healthy controls.
Secondary Outcomes
- [18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan(Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 6 months)
- [11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan(Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 6 months)