Multimodal Imaging Outcome Measures for ALS (Image ALS)

Phase 1

Terminated

• Conditions: ALS
• Interventions: Drug: [11C]-PBR28

• Registration Number: NCT04490096
• Lead Sponsor: University of Pennsylvania

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2020-06-24
• Study First Submitted QC: 2020-07-27
• Study First Posted: 2020-07-28
• Study Start: 2021-02-25
• Primary Completion: 2022-03-17
• Study Completion: 2022-03-17
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-04
• Last Update Posted: 2022-04-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
[11C]-PBR28 ALS	[11C]-PBR28	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.

Primary Outcome Measures

Name	Time	Method
Volume measurement (cubic mm) of brain regions using MRI	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	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	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 Outcome Measures

Name	Time	Method
[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	\[18F\]-FDG signal measurement (Standard Uptake Value or SUV) of \[18F\]-FDG PET for ALS patients at PENN only.
[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	\[11C\]-PBR28 signal measurement (Standard Uptake Value or SUV) of \[11C\]-PBR28 PET for ALS patients at PENN only.

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States