MRI Biomarkers in ALS

• ClinicalTrials.gov Identifier: NCT02405182
• Recruitment Status: Completed
• First Posted: April 1, 2015
• Last Update Posted: December 7, 2020
• Sponsor: University of Alberta
• Collaborators: University of Calgary; Western University, Canada; McGill University; University of Toronto
• Information provided by (Responsible Party): Sanjay Kalra, University of Alberta

Tracking Information

• First Submitted Date: February 27, 2015
• First Posted Date: April 1, 2015
• Last Update Posted Date: December 7, 2020
• Actual Study Start Date: September 2014
• Actual Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 31, 2015)

Change in neuronal and white matter integrity measures. [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 31, 2015)

Correlation of neuronal and white matter integrity measures with clinical indices. [ Time Frame: 30 months ]

Secondary analyses will involve MRI comparison to clinical measures both at the time of the baseline scan and over time.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MRI Biomarkers in ALS
• Official Title: Magnetic Resonance Imaging Biomarkers in Amyotrophic Lateral Sclerosis

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.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.

Condition

• Amyotrophic Lateral Sclerosis
• ALS
• Motor Neuron Diseases

Intervention

Other: Magnetic Resonance Imaging

Other Name: MRI

Study Groups/Cohorts

• Patients
  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.
  Intervention: Other: Magnetic Resonance Imaging
• Controls
  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.
  Intervention: Other: Magnetic Resonance Imaging

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 3, 2019): 145
• Original Estimated Enrollment (submitted: March 31, 2015): 195
• Actual Study Completion Date: April 1, 2019
• Actual Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT02405182
• Other Study ID Numbers: RES0013831
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sanjay Kalra, University of Alberta
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Alberta
• Original Study Sponsor: Same as current

Collaborators

• University of Calgary
• Western University, Canada
• McGill University
• University of Toronto

Investigators

• Principal Investigator: Sanjay Kalra, MD, FRCPC; University of Alberta

• PRS Account: University of Alberta
• Verification Date: December 2020