Offsetting Hippocampal Degeneration in m-sTBI

Traumatic Brain Injury Clinical Trial

— m-sTBI  

Official title:

Offsetting Hippocampal Degeneration in Moderate to Severe TBI

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03727334
• Other study ID #: H17-03544
• Status: Recruiting
• Phase: N/A
• Start date: July 25, 2019
• Est. completion date: July 2024

Study information

• Verified date: May 2023
• Source: University of British Columbia
• Contact: Nishtha Parag, BSc
• Phone: 604-418-4160
• Email: nishthap[@]psych.ubc.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: July 2024
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Degeneration
• Memory; Loss, Mild, Following Organic Brain Damage
• Traumatic Brain Injury

Intervention

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.

Locations

Country	Name	City	State
Canada	GF Strong Rehabilitation Centre	Vancouver	British Columbia
Canada	Vancouver General Hopsital	Vancouver	British Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of British Columbia	University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Primary	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.	Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Primary	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.	Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Primary	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.	Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Secondary	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 ß-40 and amyloid ß-42 will be assayed using Quanterix reagents on the Simoa HD-1 platform.	Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury
Secondary	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.	Time-point 1: 7 months post-injury and Time-point 2: 12 months post-injury