Clinical trial NCT03362658: Novel MRI Biomarkers for Monitoring Disease Progression in ALS
Official title: Novel MRI Biomarkers for Monitoring Disease Progression in ALS
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Keywords: Magnetic Resonance Imaging
MRI
Biomarker
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: University of Calgary
name: Western University, Canada
name: McGill University
name: University of Toronto
name: University of British Columbia
name: Laval University
name: University of Miami
name: University of Utah
First posted: 2017-12-05
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in cortical thickness in millimetres.
timeFrame: 8 months
measure: Change in DTI indices (unitless).
timeFrame: 8 months
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Calgary
country: Canada
facility: University of Calgary / Heritage Medical Research Clinic
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia / GF Strong Rehab Centre
state: British Columbia
city: London
country: Canada
facility: Western University / London Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University of Toronto / Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University / Montreal Neurological Institute and Hospital
state: Quebec
city: Quebec City
country: Canada
facility: Laval University
state: Quebec
Study officials:
affiliation: FRCPC
name: Sanjay Kalra, MD
role: PRINCIPAL_INVESTIGATOR
References: