Back to resultsOffsetting Hippocampal Degeneration in m-sTBI (m-sTBI)
Primary Purpose
Traumatic Brain Injury, Degeneration, Memory; Loss, Mild, Following Organic Brain Damage
Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Online Spatial Navigation Training
Sponsored by
About this trial
This is an interventional treatment trial for Traumatic Brain Injury
Eligibility Criteria
Inclusion Criteria:
An acute care diagnosis of TBI as determined by a medical professional, 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
- 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)
- You are experiencing language impairments (i.e., aphasia) from your injury
Sites / Locations
- Vancouver General Hopsital
- GF Strong Rehabilitation CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Treatment
Control
Arm Description
For the treatment arm, the participants will complete the intervention protocol following the first in-person study visit 7 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, 5 days a week.
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.
Outcomes
Primary Outcome Measures
Online Spatial Navigation Intervention Test Scores: Change in Spatial Learning Ability
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.
Online Spatial Navigation Intervention Test Scores: Change in Cognitive Map Formation
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.
Online Spatial Navigation Intervention Test Scores: Change in Pattern Separation
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.
Online Spatial Navigation Intervention Test Scores: Change in Pattern Completion
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
Neuronal injury biomarker predictors in serum and plasma samples
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.
Gliosis and inflammation biomarker predictors in serum samples
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.
Full Information
NCT ID
NCT03727334
First Posted
October 3, 2018
Last Updated
May 8, 2023
Sponsor
University of British Columbia
Collaborators
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT03727334
Brief Title
Offsetting Hippocampal Degeneration in m-sTBI
Acronym
m-sTBI
Official Title
Offsetting Hippocampal Degeneration in Moderate to Severe TBI
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 25, 2019 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
Collaborators
University Health Network, Toronto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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; 7 months post-TBI and 12 months post-TBI.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury, Degeneration, Memory; Loss, Mild, Following Organic Brain Damage
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Outcomes Assessor
Masking Description
The psychometrist will be blind to the arm the participant is assigned to.
Allocation
Randomized
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment
Arm Type
Experimental
Arm Description
For the treatment arm, the participants will complete the intervention protocol following the first in-person study visit 7 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, 5 days a week.
Arm Title
Control
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Behavioral
Intervention Name(s)
Online Spatial Navigation Training
Intervention Description
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.
Primary Outcome Measure Information:
Title
Online Spatial Navigation Intervention Test Scores: Change in Spatial Learning Ability
Description
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.
Time Frame
Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Title
Online Spatial Navigation Intervention Test Scores: Change in Cognitive Map Formation
Description
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.
Time Frame
Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Title
Online Spatial Navigation Intervention Test Scores: Change in Pattern Separation
Description
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.
Time Frame
Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Title
Online Spatial Navigation Intervention Test Scores: Change in Pattern Completion
Description
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.
Time Frame
Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Secondary Outcome Measure Information:
Title
Neuronal injury biomarker predictors in serum and plasma samples
Description
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.
Time Frame
Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Title
Gliosis and inflammation biomarker predictors in serum samples
Description
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.
Time Frame
Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
An acute care diagnosis of TBI as determined by a medical professional, 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
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)
You are experiencing language impairments (i.e., aphasia) from your injury
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nishtha Parag, BSc
Phone
604-418-4160
Email
nishthap@psych.ubc.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William Panenka, MD
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Robin Green, PhD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vancouver General Hopsital
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Individual Site Status
Enrolling by invitation
Facility Name
GF Strong Rehabilitation Centre
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 2G9
Country
Canada
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Offsetting Hippocampal Degeneration in m-sTBI
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