Clinical trial NCT04490096: Multimodal Imaging Outcome Measures for ALS (Image ALS)
Official title: Multimodal Imaging Outcome Measures for ALS (Image ALS)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: ALS
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: Biogen
name: University of Miami
name: University of Kansas
First posted: 2020-07-28
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.

Eligibility 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

Primary outcomes:
measure: Volume measurement (cubic mm) of brain regions using MRI
timeFrame: Change from baseline volume measurement (cubic mm) at 6 months
measure: Volume measurement (cubic mm) of brain regions using MRI
timeFrame: Change from baseline volume measurement (cubic mm) at 12 months
measure: Thickness measurement (mm) of brain regions using MRI
timeFrame: Change from baseline thickness measurement (mm) at 6 months
measure: Thickness measurement (mm) of brain regions using MRI
timeFrame: Change from baseline thickness measurement (mm) at 12 months
measure: Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI
timeFrame: Change from baseline cerebral blood flow measurement (mL of blood/100g per minute) at 6 months
measure: Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI
timeFrame: Change from baseline cerebral blood flow measurement (mL of blood/100g per minute at 12 months
Secondary outcomes:
measure: [18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan
timeFrame: Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 3 months
measure: [18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan
timeFrame: Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 6 months
measure: [11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan
timeFrame: Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 3 months
measure: [11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan
timeFrame: Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 6 months
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Corey McMillan, PhD
role: PRINCIPAL_INVESTIGATOR
References: