Multimodal Imaging Outcome Measures for ALS (Image ALS)

University of Pennsylvania

Status and phase: Terminated; Phase 1

Conditions: ALS

Treatments: Drug: [11C]-PBR28

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04490096

834366

Details and patient eligibility

About

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)

Full 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.

Enrollment: 2 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria for participants in PET sub-study (Penn Only):

1. Enrolled in the MRI study at Penn.
2. Willing to participate in a 30 minute [18F]-FDG and 1.5 hour [11C]-PBR28 PET scan within 15 days baseline and longitudinally at the 3-month and 6-month follow-up visits, if able.

Exclusion criteria for PET sub-study participants:

1. Females who are pregnant at the time of study visits will not be eligible for the PET sub-study; urine or serum pregnancy test will be performed in women of child-bearing potential at each of the baseline, 3-month, and 6-month study visit.
2. Homozygous genotype for the threonine-associated substitution allele (A) in the rs6971 polymorphism.
3. Blood glucose less than or equal to 250 mg/dl, or at the discretion of the authorized user

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 1 patient group

[11C]-PBR28 ALS

Other group

Description:

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.

Treatment:

Drug: [11C]-PBR28