MRI Biomarkers in ALS

Completed

• Conditions: Amyotrophic Lateral Sclerosis; Motor Neuron Diseases; ALS
• Interventions: Other: Magnetic Resonance Imaging

• Registration Number: NCT02405182
• Lead Sponsor: University of Alberta

Brief Summary

Amyotrophic lateral sclerosis (ALS) is a disabling and rapidly progressive neurodegenerative disorder. There is no treatment that significantly slows progression. Increasing age is an important risk factor for developing ALS; thus, the societal impact of this devastating disease will become more profound as the population ages. A significant hurdle to finding effective treatment has been an inability to accurately measure brain degeneration in humans. Advanced magnetic resonance imaging (MRI) techniques hold promise in this respect, and may assist in aiding diagnosis and the efficient testing of new drugs.

Different MRI features of brain degeneration will be measured in a large sample of patients with ALS. The study will operate within the Canadian ALS Neuroimaging Consortium (CALSNIC). CALSNIC is a clinical research platform comprised of ALS clinics with standardized clinical and neuroimaging protocols.

Detailed Description

This study will use advanced Magnetic Resonance Imaging (MRI) techniques to measure brain changes in ALS and related neurological conditions. Results from cognitive and neurological tests will be compared to the MRI. It is believed that these techniques will reveal changes in the brain that will help us understand normal brain function and the symptoms of neurological diseases as seen in ALS, as well to provide an objective measurement of degeneration (which is called a biomarker). This could improve not only the process by which new drugs for the treatment of neurological diseases are evaluated, but also how health care professionals address the needs of patients with these diseases.

Furthermore, a biomarker may give insight into the biological factors related to the diverse and variable clinical features amongst different patients.

Subjects will be recruited from ALS clinics that are a part of the Canadian ALS Neuroimaging Consortium (CALSNIC). Patients will have a diagnosis of ALS, PLS, PMA, or FTD. Healthy controls will be age and gender matched to patients. Subjects will visit their respective sites to undergo a clinical evaluation and an MRI. Follow up visits will occur at approximately 3-6 month intervals. Most subjects will have 2 follow up visits; more visits may occur for subjects who are physically able to continue in the protocol.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2014-09
• Study First Submitted: 2015-02-27
• Study First Submitted QC: 2015-03-31
• Study First Posted: 2015-04-01
• Primary Completion: 2019-03
• Study Completion: 2019-04-01
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-04
• Last Update Posted: 2020-12-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 145

Inclusion Criteria

• Patients will be adults with a diagnosis of motor neuron disease (MND), including those with ALS, PLS, and PMA, and as well frontotemporal dementia (FTD) without motor neuron signs.
• Healthy controls over the age of 40 will also be recruited and will be age- and gender-matched to patients.

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Exclusion Criteria

• Subjects with other psychiatric/CNS illnesses such as Major Depressive Disorder, Schizophrenia, and Bipolar disorder, and those with significant head injury.
• Subjects ineligible for MRI investigation due to a pacemaker or other metallic foreign body, or significant claustrophobia that could affect the ability to have an MRI scan.

These exclusion criteria will also apply to controls.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients	Magnetic Resonance Imaging	ALS patients (as well as patients with other motor neuron diseases such PLS and PMA) will be recruited from ALS clinics under the direction of ALS neurologists who are participating in this study. ALS patients should meet research criteria for possible, probable, probable laboratory-supported, or definite ALS. Patients with a history of CNS disease (e.g. stroke, head injury) or significant psychiatric disease will be ineligible. Patients must be able to undergo a brain MRI for approximately an hour.
Controls	Magnetic Resonance Imaging	Healthy controls who are age and gender matched to patients will be recruited. Controls with a history of CNS disease (e.g. stroke, head injury) or significant psychiatric disease will be ineligible. Controls must be able to undergo a brain MRI for approximately an hour.

Primary Outcome Measures

Name	Time	Method
Change in neuronal and white matter integrity measures.	24 months	The primary analysis will evaluate changes in the brain using various advanced MRI techniques at baseline and specified follow up periods. Patients and controls scans will be compared.

Secondary Outcome Measures

Name	Time	Method
Correlation of neuronal and white matter integrity measures with clinical indices.	30 months	Secondary analyses will involve MRI comparison to clinical measures both at the time of the baseline scan and over time.

Trial Locations

Locations (6)

University of Toronto / Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

McGill University / Montreal Neurological Institute and Hospital; 🇨🇦 Montreal, Quebec, Canada

University of Calgary / Heritage Medical Research Clinic; 🇨🇦 Calgary, Alberta, Canada

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

University of British Columbia / GF Strong Rehab Centre; 🇨🇦 Vancouver, British Columbia, Canada

Western University / London Health Sciences Centre; 🇨🇦 London, Ontario, Canada