Imaging and BioFluid Biomarkers in Amyotrophic Lateral Sclerosis

NCT02559869 | Completed

• 1 other identifier: 2015P000140
• Study Type: observational
• Target: 86
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multicenter, 18-month study, which aims to identify imaging and biofluid biomarkers in people with ALS to expand the understanding of ALS pathology, treatment targets, disease progression, and anatomical differences between different disease phenotypes. This pilot project is tailored to produce imaging tools that will allow researchers to conduct future ALS clinical trials more efficiently which may in turn impact the pace for ALS drug discovery.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Biofluid; ALS; MRI; PET; Imaging; Biomarkers; Amyotrophic Lateral Sclerosis; TRACK ALS; pathology

Outcome Measures

Primary Outcomes (3)

• Measure & localize brain inflammation in people with ALS via [18F] GE-180 PET imaging.

  Aim 1 will be accomplished by obtaining \[18F\] GE-180 PET imaging from 25 people with ALS compared to 25 age, gender, and binding affinity matched healthy volunteers.

  12 months

• Define anatomical, structural, and functional changes in the brain via MRI of ALS Subjects vs. Healthy Controls at Baseline

  Aim 1 will be accomplished by obtaining state of-the-art MRI acquisition sequences from 50 people with ALS compared to 50 MRI age- and gender-matched healthy volunteers.

  12 months

• Determine systemic inflammatory factors that may modify the progression or other clinical or imaging correlates of ALS.

  Blood from 100 subjects will be studied to quantitate circulating pro- and anti-inflammatory monocyte/macrophage and T cells, with results to be correlated with neuroimaging and evaluated as potential biomarkers of disease progression.

  12 months

Secondary Outcomes (2)

• Determine the longitudinal changes in brain inflammation in people with ALS in correlation with ALS severity and rate of progression.

  12 months

• Determine the longitudinal changes in the anatomical, structural, and functional measures in people with ALS, and build ALS prediction models using the clinical and MRI data.

  12 months

Study Arms (2)

Amyotrophic Lateral Sclerosis (ALS)

Subjects will be diagnosed with possible, probable, probable-lab supported, or definite ALS.

Drug: [18F] GE-180

Healthy Controls

Subjects with no known neurological disorder.

Drug: [18F] GE-180

Interventions

[18F] GE-180 DRUG

PET Tracer Ligand

Also known as: ligand, PET Tracer

Amyotrophic Lateral Sclerosis (ALS); Healthy Controls

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Approximately 200 subjects will be screened and approximately 100 subjects will be enrolled. Fifty (50) subjects will be diagnosed with possible, probable, probable-lab supported, or definite ALS, fifty (50) subjects will have no known neurological disease.

You may qualify if:

• Study subjects meeting all of the following criteria will be allowed to enroll in the study:
• Male or female, aged 18 to 80
• Medically safe to undergo MRI scans
• Able to safely lie supine for at least 90 minutes in the opinion of the Site Investigator
• Capable of providing informed consent and following trial procedures
• Geographically accessible to the site
• ALS subjects must also meet the following criteria:
• Sporadic or familial ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by modified El Escorial criteria
• ALS Cognitive Behavioral Screen score \>10 on the cognitive scale and/or \>32 on the behavioral scale
• Those ALS subjects participating in the optional lumbar puncture portion of the study must also meet the following criteria:
• \. Subjects medically able to undergo lumbar puncture (LP) as determined by the investigator (i.e., no bleeding disorder, allergy to local anesthetics, a skin infection at or near the LP site, or evidence of high intracranial pressure).
• For those subjects participating in the PET scan portion of the study, subjects must also meet the following criteria:
• Medically safe to undergo PET scans
• No prior radiation exposure that exceeds the site's current guidelines
• No known allergy to any components of the tracer

You may not qualify if:

• Study subjects meeting any of the following criteria during screening evaluations will be excluded from entry into the study:
• Any contraindication to undergo MRI studies such as
• History of a cardiac pacemaker or pacemaker wires
• Metallic particles in the body
• Vascular clips in the head
• Prosthetic heart valves
• Claustrophobia
• Diagnosis of Parkinson's disease or Alzheimer's disease
• Diagnosis of renal failure
• Have active or chronic autoimmune disease (such as hepatitis or HIV), infection, or taking immunosuppressive medications such as steroids, cyclophosphamide, etc.
• Presence of diaphragm pacing system (DPS)
• The presence of unstable psychiatric disease, cognitive impairment, or dementia that would impair ability of the subject to provide informed consent, according to SI judgment
• Pregnant women or women currently breastfeeding
• Anything that, in the opinion of the investigator, would place the subject at increased risk or preclude the subject's full compliance with or completion of the study
• In addition, any subject meeting any of the following criteria during screening evaluations will be excluded from entry into the PET portion of the study:

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• The Methodist Hospital Research Institute: collaborator
• Cedars-Sinai Medical Center: collaborator
• ALS Association: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Related Links

• NEALS website (Northeast ALS Consortium)

Biospecimen

Retention: SAMPLES WITH DNA

iPSC Line Generation, DNA, Inflammatory Markers, Plasma, CSF

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

GE-180; Ligands

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Laboratory Chemicals; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Officials

• Suma Babu, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Joseph Masdeu, MD, PhD

  Houston Methodist Neurological Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Co-Principal Investigator

Study Record Dates

• First Submitted: September 23, 2015
• First Posted: September 24, 2015
• Study Start: November 1, 2015
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: May 21, 2020

Record last verified: 2020-05

Locations

US (2)