Multimodal Imaging Outcome Measures for ALS (Image ALS)

NCT04490096 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 834366
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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)

Conditions

ALS

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (4)

• [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 3 months

• [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 3 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

Study Arms (1)

[11C]-PBR28 ALS

OTHER

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.

Drug: [11C]-PBR28

Interventions

[11C]-PBR28 DRUG

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.

[11C]-PBR28 ALS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Enrolled in the MRI study at Penn.
• 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.

You may not qualify if:

• 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.
• Homozygous genotype for the threonine-associated substitution allele (A) in the rs6971 polymorphism.
• Blood glucose less than or equal to 250 mg/dl, or at the discretion of the authorized user

Sponsors & Collaborators

• University of Pennsylvania: lead
• Biogen: collaborator
• University of Miami: collaborator
• University of Kansas: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine

Study Officials

• Corey McMillan, PhD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: July 28, 2020
• Study Start: February 25, 2021
• Primary Completion: March 17, 2022
• Study Completion: March 17, 2022
• Last Updated: April 12, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)