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Offsetting Hippocampal Degeneration in m-sTBI (m-sTBI)

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ClinicalTrials.gov Identifier: NCT03727334
Recruitment Status : Recruiting
First Posted : November 1, 2018
Last Update Posted : April 16, 2019
Sponsor:
Collaborator:
University Health Network, Toronto
Information provided by (Responsible Party):
William Panenka, University of British Columbia

Brief Summary:
The goal of this study is to establish the feasibility of an intervention designed to improve memory in patients who have experienced a moderate or severe traumatic brain injury (m-sTBI) and to examine its effect on brain structures.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Degeneration Memory; Loss, Mild, Following Organic Brain Damage Behavioral: Online Spatial Navigation Training Not Applicable

Detailed Description:
The purpose of this study is to establish the feasibility of a novel intervention, and explore biomarker predictors of neurodegeneration and response to the proposed intervention. This 16 week intervention utilises allocentric spatial navigation tasks to improve memory and counteract hippocampal neurodegeneration. This intervention will be administered in combination with neuropsychological assessments, MR imaging, and the analysis of genomic variants at two time points; 6 months post-TBI and 12 months post-TBI.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a randomized two-armed study, comprised of a treatment arm and a control arm. Given the small numbers and the potentially slow rate of recruitment, the investigators will employ simple rather than block randomization. To minimize selection bias, allocation to group will be concealed (i.e., with assignment unpredictable and unchangeable) using software that randomizes each patient upon confirmation of eligibility. Patients will not be blind to group assignment, but the psychometrist completing behavioural outcomes will be kept blind to group assignment.
Masking: Single (Outcomes Assessor)
Masking Description: The psychometrist will be blind to the arm the participant is assigned to.
Primary Purpose: Treatment
Official Title: Offsetting Hippocampal Degeneration in Moderate to Severe TBI
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020

Arm Intervention/treatment
Experimental: Treatment
For the treatment arm, the participants will complete the intervention protocol following the first in-person study visit 6 months post-injury. The intervention involves 16 weeks of online, in-home spatial navigation training. During the 16 weeks, the participant will complete exercises for 1 hour/day, every other day.
Behavioral: Online Spatial Navigation Training
Participants complete training tasks that test their spatial navigational abilities, cognitive map formation, and pattern separation. These training tasks involve map drawing, vector mapping, proximity judgments, and navigating with blocked routes.

No Intervention: Control
The control arm participants will receive their typical standard of care; they will not complete the intervention but will complete all of the in-person visits at the same post-injury time-points as the treatment group.



Primary Outcome Measures :
  1. Online Spatial Navigation Intervention Test Scores: Change in Spatial Learning Ability [ Time Frame: Time-point 1: 6 months post-injury and Time-point 2: 10 months post-injury ]
    Participants complete online spatial navigation training 5 days per week for 16 weeks. Improvement in spatial learning ability will be assessed based on the accuracy of answers to questions regarding the reproduction of spatial elements, the direction and proximity of certain landmarks, and describing the most efficient route from point A to point B. Improvement will be assessed at the end of each week and at the end of the intervention. The raw scores range from 0-15, with higher scores indicating better spatial learning ability.

  2. Online Spatial Navigation Intervention Test Scores: Change in Cognitive Map Formation [ Time Frame: Time-point 1: 6 months post-injury and Time-point 2: 10 months post-injury ]
    Participants complete online spatial navigation training 5 days per week for 16 weeks. Improvement in cognitive map formation will be assessed based on the number of trails required by the participant to learn landmark placements and based on the accuracy of the participant's navigation to a specific destination. The raw scores range from 1-21 and 0-10, respectively. A decrease in the number of trials required by the participant and an increase in navigation accuracy both correspond to an improvement in cognitive map formation.

  3. Online Spatial Navigation Intervention Test Scores: Change in Pattern Separation [ Time Frame: Time-point 1: 6 months post-injury and Time-point 2: 10 months post-injury ]
    Measurement of pattern separation abilities are assessed in a task requiring the participant to differentiate memories in order to prevent interference from overlapping details. The following three variables are taken into account: i) percent correct ii) the discriminating value and iii) bias metric. Percent correct and bias metric are given as a percentage values (e.g., 80.63%) and the discriminating variable is given as a raw rate (e.g., 0.67). An improvement in pattern separation abilities are determined by an increase in percent correct and discrimination values from pre- to post-intervention. An increase in bias metric from pre- to post-intervention reflects an increased tendency for pattern separation.

  4. Online Spatial Navigation Intervention Test Scores: Change in Pattern Completion [ Time Frame: Time-point 1: 6 months post-injury and Time-point 2: 10 months post-injury ]
    Measurement of pattern completion abilities are assessed in a task designed to probe pattern completion by presenting partial retrieval cues at different levels of degradation. The following variables are taken into account: i) accuracy for learned stimuli given as a percentage value (i.e., correctly selecting the name of the scene) ii) accuracy for new stimuli given as a percentage value (i.e., correctly indicating the stimuli is novel) and iii) bias measure. The bias measure is obtained by subtracting the learned stimuli accuracy score from the new stimuli accuracy score. An increase for both accuracy measures from pre- to post-intervention corresponds to improvement on recognition memory. An increase in bias measure reflects an increased tendency for pattern separation.


Secondary Outcome Measures :
  1. Neuronal injury biomarker predictors in serum and plasma samples [ Time Frame: Time-point 1: 6 months post-injury and Time-point 2: 12 months post-injury ]
    The investigators will be analysing biomarkers in serum and plasma samples in relation to traumatic brain injuries. This will allow the investigators to generate hypotheses concerning the relationship between blood biomarkers and neuronal injury. Serum neurofilament light chains (NF-L), total tau, amyloid β-40 and amyloid β-42 will be assayed using Quanterix reagents on the Simoa HD-1 platform.

  2. Gliosis and inflammation biomarker predictors in serum samples [ Time Frame: Time-point 1: 6 months post-injury and Time-point 2: 12 months post-injury ]
    The investigators will be analysing biomarkers in serum samples in relation to gliosis and inflammation. This will allow the investigators to generate hypotheses concerning the relationship between blood biomarkers and neuroimmune response. Serum monocyte chemoattractant protein-1 (MCP-1) will be assayed using MesoScale Discovery reagents on the Sector S600 platform and glial fibrillary acidic protein (GFAP) will be assayed using Quanterix reagents on the Simoa HD-1 platform.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • An acute care diagnosis of TBI as indicated by

    • Post-traumatic amnesia duration of 24 hours or more, and/or lowest Glasgow Coma Scale score of < 13
    • Positive clinical CT or MRI scan
  • Aged 18 to 65
  • Fluent in English
  • Have the competency for fully informed consent by 6 months post-injury
  • Have basic computer skills
  • A resident of the Greater Vancouver Area
  • Have functional use of one upper extremity
  • Have access to the internet

Exclusion Criteria:

  • A neurological disorder other than TBI (e.g., stroke, dementia, tumor, neurodevelopmental disorder) impairing baseline awareness, cognition, or validity of follow-up and outcome assessment.
  • A systemic condition (e.g., lupus, diabetes, rheumatoid arthritis).
  • Any contraindications to magnetic resonance imaging (MRI)
  • A diagnosed learning disability or learning problems (e.g., dyslexia, language processing disorder, non-verbal learning disabilities, perceptual/motor deficits, attention deficit disorders etc.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03727334


Contacts
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Contact: Angela Aquino, BSc 778-898-9117 angela.aquino@ubc.ca
Contact: Victoria Purcell 604-618-3471 victoria.purcell@alumni.ubc.ca

Locations
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Canada, British Columbia
Vancouver General Hopsital Enrolling by invitation
Vancouver, British Columbia, Canada, V5Z 1M9
GF Strong Rehabilitation Centre Recruiting
Vancouver, British Columbia, Canada, V5Z 2G9
Sponsors and Collaborators
University of British Columbia
University Health Network, Toronto
Investigators
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Principal Investigator: William Panenka, MD University of British Columbia
Principal Investigator: Robin Green, PhD University Health Network, Toronto

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Responsible Party: William Panenka, Principal Investigator, University of British Columbia
ClinicalTrials.gov Identifier: NCT03727334     History of Changes
Other Study ID Numbers: H17-03544
First Posted: November 1, 2018    Key Record Dates
Last Update Posted: April 16, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wounds and Injuries