Novel MRI Biomarkers for Monitoring Disease Progression in ALS

Routine MRI is normal in motor neuron diseases such as ALS. However, advanced MRI techniques can provide an objective measure of degeneration (a "biomarker") by examining brain structure, wiring, chemistry, and function. We will develop and evaluate novel MRI techniques that could improve our understanding of ALS and provide a means to diagnose it sooner and monitor its progression. Importantly, we expect these techniques to improve how new drugs are tested, which may lead to the more rapid discovery of a treatment for ALS.

Each participant will have 3 MRI scans over a period of 8 months, along with neurological and cognitive evaluations. Study visits will take 2 - 3 hours. MRI is a safe technique that does not involve radiation.

Study Overview

• Status: Active, not recruiting
• Conditions: Motor Neuron Disease; Amyotrophic Lateral Sclerosis

Detailed Description

Current clinical measures of disease burden have suboptimal sensitivity to disease progression in ALS. A biomarker would play an essential role in the evaluation of novel therapeutics, leading to the realization of effective treatments faster. Magnetic resonance imaging (MRI) holds promise as a non-invasive source of biomarkers in ALS. In this study data is collected from a national imaging platform (the Canadian ALS Neuroimaging Consortium [CALSNIC]) using standardized MRI and clinical protocols.

CALSNIC was founded with the objective to validate MRI biomarkers on a standardized multi-centre platform. CALSNIC is a multidisciplinary group of scientists at 7 centres across Canada. The first CALSNIC study entitled "MRI Biomarkers in ALS" (CALSNIC-1) is ongoing and slated to finish recruitment in 2017.

This study ("Novel MRI Biomarkers for Monitoring Disease Progression in ALS", CALSNIC-2) is a new project that will evaluate novel MRI biomarkers using advanced imaging acquisition and processing methods. The specific aims of CALSNIC-2 are 1) to establish a standardized MRI and clinical protocol across the 7 centres, and 2) to validate MRI measures with clinical measures of disease burden and progression.

It is anticipated that the project will lead to the discovery of MR-based biomarkers of cerebral degeneration that can be applied across different centres and hence, can assist with drug development. Secondly, this project will expand CALSNIC to include more centres and provide opportunities for collaborative and multidisciplinary translational research on a national scale.

• Study Type: Observational
• Enrollment (Actual): 119

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary / Heritage Medical Research Clinic
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • University of Toronto / Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • McGill University / Montreal Neurological Institute and Hospital
    • Québec, Quebec, Canada, G1V 0A6
      • Laval University
• United States
  • Florida
    • Miami, Florida, United States
      • University of Miami
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

1. Patients with a diagnosis of motor neuron disease (MND). This includes the diagnoses of amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), and progressive muscular atrophy (PMA).
2. Patients with frontotemporal dementia (FTD) with or without motor neuron signs.

Description

Inclusion Criteria:

• Patients with a suspected or confirmed diagnosis as described in Study Populations
• For those with a diagnosis of ALS, patients will be considered with an El Escorial classification of suspected, possible, probable, probable lab-supported, and definite ALS.
• Patients 18 years of age or older
• Healthy controls over the age of 40.
• Be able to lie in an MRI machine for approximately 60 minutes

Exclusion Criteria:

• Subjects with psychiatric/CNS illnesses such as Major Depressive Disorder, Schizophrenia, and Bipolar disorder.
• Subjects with significant head injury or other neurological disease (stroke, brain tumour).
• Subjects ineligible for MRI investigation due to a pacemaker or other metallic foreign body.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients; ALS patients (as well as patients with other related disorders such PLS, PMA, and ALS-FTD) will be recruited from ALS clinics under the direction of neurologists who are participating in this study. ALS patients should meet research criteria for suspected, possible, probable, probable laboratory supported, or definite ALS.
Controls; Healthy controls who are age and gender matched to patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cortical thickness in millimetres.	This primary analysis will evaluate neuronal integrity at baseline and specified follow up periods. Patients and controls scans will be compared.	8 months
Change in DTI indices (unitless).	This primary analysis will evaluate white matter integrity at baseline and specified follow up periods. Patients and controls scans will be compared.	8 months

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: University of British Columbia; McGill University; University of Miami; University of Toronto; University of Calgary; University of Utah; Western University, Canada; Laval University
• Investigators: Principal Investigator: Sanjay Kalra, MD, FRCPC

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 18, 2017
• First Submitted That Met QC Criteria: November 29, 2017
• First Posted (Actual): December 5, 2017

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: MRI; Biomarker; Magnetic Resonance Imaging
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Nutritional and Metabolic Diseases; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: RES0027887