Clinical trial NCT02405182: MRI Biomarkers in ALS
Official title: Magnetic Resonance Imaging Biomarkers in Amyotrophic Lateral Sclerosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Amyotrophic Lateral Sclerosis
ALS
Motor Neuron Diseases
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
First posted: 2015-04-01
Enrollment: 145
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects will be recruited predominantly from ALS clinics at: the University of Alberta Hospital in Edmonton; the Foothills Medical Centre in Calgary; the Sunnybrook Health Sciences Centre in Toronto; the London Health Sciences Centre in London; and the Montreal Neurological Hospital in Montreal.

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.

Eligibility criteria: 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.

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.

Primary outcomes:
measure: Change in neuronal and white matter integrity measures.
timeFrame: 24 months
Secondary outcomes:
measure: Correlation of neuronal and white matter integrity measures with clinical indices.
timeFrame: 30 months
Other outcomes:
Locations:
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
Study officials:
affiliation: University of Alberta
name: Sanjay Kalra, MD, FRCPC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ta D, Ishaque A, Srivastava O, Hanstock C, Seres P, Eurich DT, Luk C, Briemberg H, Frayne R, Genge AL, Graham SJ, Korngut L, Zinman L, Kalra S. Progressive Neurochemical Abnormalities in Cognitive and Motor Subgroups of Amyotrophic Lateral Sclerosis: A Prospective Multicenter Study. Neurology. 2021 Aug 24;97(8):e803-e813. doi: 10.1212/WNL.0000000000012367. Epub 2021 Jun 14.
citation: Kalra S, Muller HP, Ishaque A, Zinman L, Korngut L, Genge A, Beaulieu C, Frayne R, Graham SJ, Kassubek J. A prospective harmonized multicenter DTI study of cerebral white matter degeneration in ALS. Neurology. 2020 Aug 25;95(8):e943-e952. doi: 10.1212/WNL.0000000000010235. Epub 2020 Jul 9.