Multimodal Imaging Outcome Measures for ALS (Image ALS)

ALS Clinical Trial

Official title:

Multimodal Imaging Outcome Measures for ALS (Image ALS)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04490096
• Other study ID #: 834366
• Status: Terminated
• Phase: Phase 1
• Start date: February 25, 2021
• Est. completion date: March 17, 2022

Study information

• Verified date: April 2022
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: March 17, 2022
• Est. primary completion date: March 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• ALS

Intervention

Drug:
• [11C]-PBR28
A dose of = 20 mCi (approximate range for most studies is anticipated to be 5-20 mCi) of [11C]-PBR28 will be administered by IV injection to the patient under the direct supervision of a Nuclear Medicine Authorized User. A lesser activity may be injected if, in the opinion of a nuclear medicine authorized user complete imaging data could be generated. Subjects will undergo an approximately 90 minute dynamic PET/CT scan over the brain starting at approximately the same time as the [11C]-PBR-28 injection. Scans will be acquired using a Philips PET/CT time-of-flight Ingenuity scanner (Philips Healthcare, Cleveland, OH, USA). At the end of the dynamic imaging the participant will be allowed to get off the scanner.

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of Pennsylvania	Biogen, University of Kansas, University of Miami

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Volume measurement (cubic mm) of brain regions using MRI	Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.	Change from baseline volume measurement (cubic mm) at 6 months
Primary	Volume measurement (cubic mm) of brain regions using MRI	Volume measurement (cubic mm) of brain regions using MRI for ALS patients and healthy controls.	Change from baseline volume measurement (cubic mm) at 12 months
Primary	Thickness measurement (mm) of brain regions using MRI	Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.	Change from baseline thickness measurement (mm) at 6 months
Primary	Thickness measurement (mm) of brain regions using MRI	Thickness measurement (mm) of brain regions using MRI in ALS patients and healthy controls.	Change from baseline thickness measurement (mm) at 12 months
Primary	Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI	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.	Change from baseline cerebral blood flow measurement (mL of blood/100g per minute) at 6 months
Primary	Cerebral blood flow measurement (mL of blood/100g per minute) of brain regions using MRI	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.	Change from baseline cerebral blood flow measurement (mL of blood/100g per minute at 12 months
Secondary	[18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan	[18F]-FDG signal measurement (Standard Uptake Value or SUV) of [18F]-FDG PET for ALS patients at PENN only.	Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 3 months
Secondary	[18F]-FDG signal measurement (standard uptake volume or SUV) in brain regions using PET scan	[18F]-FDG signal measurement (Standard Uptake Value or SUV) of [18F]-FDG PET for ALS patients at PENN only.	Change from baseline [18F]-FDG signal measurement (standard uptake volume or SUV) at 6 months
Secondary	[11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan	[11C]-PBR28 signal measurement (Standard Uptake Value or SUV) of [11C]-PBR28 PET for ALS patients at PENN only.	Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 3 months
Secondary	[11C]-PBR28 signal measurement (standard uptake volume or SUV) in brain regions using PET scan	[11C]-PBR28 signal measurement (Standard Uptake Value or SUV) of [11C]-PBR28 PET for ALS patients at PENN only.	Change from baseline [11C]-PBR28 signal measurement (standard uptake volume or SUV) at 6 months