Clinical trial NCT04882215: Integrated PRocess and StrategieS Training: I-PRESS Training
Official title: Development and Evaluation of a Novel Treatment Intervention for People With Acquired Brain Injury
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Acquired Brain Injury
Keywords: Traumatic Brain Injury
Stroke
executive dysfunction
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: University of Glasgow
First posted: 2021-05-11
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: There is a pressing need to develop more effective interventions to remediate cognitive deficits in highly prevalent disabling conditions such as stroke, head injury and other forms of acquired brain injury (ABI). Neuropsychological rehabilitation interventions developed in a clinical setting have shown some beneficial effects, but the effectiveness of clinical interventions have potential to be enhanced if informed by findings from cognitive neuroscience. Research into cognitive training using methods such as functional magnetic resonance imaging (fMRI) has contributed to an understanding of factors that promote changes in brain function, but this approach seldom includes individuals with brain damage or cognitive deficits. Its potential for application with clinical populations is therefore uncertain, meaning that people who may benefit do not have access to interventions that may improve their health and wellbeing.

The proposed research brings together methods from neuropsychological rehabilitation and cognitive neuroscience to investigate 1) the feasibility of, and effect sizes arising from, combining an existing clinical intervention targeting mental strategies with an adaptive training programme targeting core cognitive processes, and 2) whether the novel treatment combination promotes changes in brain function that are detectable using fMRI.

This project will develop and evaluate a training intervention that aims to improve outcomes from a strategy-based rehabilitation intervention, Goal Management Training (GMT), by adding process-based cognitive training with adaptive difficulty to enhance the executive function of working memory updating (WMU). People with ABI (n=32) will complete 9 sessions of GMT, a recommended treatment for deficits in frontal-lobe executive functions, with the addition of 8 WMU training sessions with or without adaptive training. Measures of feasibility, acceptability, and fidelity will be taken, and effect sizes of differences in pre- to post-training changes on neural, cognitive, and functional measurements will be determined by comparing two experimental groups in which difficulty of the WMU training tasks either adaptively increases in response to performance or is fixed.

Detailed description: Globally, stroke and head injury are leading causes of disability. Deficits in cognitive functions are common in these conditions, including impairment in frontal-lobe 'executive' functions such as working memory and the ability to solve problems, plan, and regulate actions in order to achieve intended goals. These deficits affect individuals' ability to live independently, work, and maintain social relationships. We propose that improving outcomes for people with acquired brain injury (ABI) requires an interdisciplinary approach in which neuropsychological rehabilitation and cognitive neuroscience complement one another.

In neuropsychological rehabilitation, interventions are classified as 'restorative' (restoration of underlying core cognitive processes including executive functions) or 'compensatory' (compensation of function through the use of external aids or learned strategies). Clinical guidelines recommend the use of 'meta-cognitive strategy training' for the treatment of deficits in frontal-lobe executive functions. Goal Management Training (GMT) is one such validated meta-cognitive strategy. GMT trains compensatory mental strategies to manage attention during multi-step tasks. GMT has been evaluated behaviourally in randomised controlled trials with positive, albeit modest, outcomes in individuals with ABI.

In cognitive neuroscience, an emerging research area concerns experience-induced neural changes referred to as neural plasticity. These may involve neural changes in: 1) task-based functional activation patterns, i.e. activity increases, decreases, or reorganisation, 2) brain structure, i.e., grey matter and white matter volume changes and 3) functional connectivity, i.e. changes in connectivity between brain regions that are recruited for a mental procedure as well as changes in the strength and magnitude.

Neuroimaging studies have demonstrated that programmes to train core cognitive processes including working memory (WM) executive functions can drive changes both in behavioural and neural measures. Performance gains after process-based training have been observed by several authors employing different training tasks and including both younger and older populations. In addition, generalisation to broad cognitive abilities such as reasoning, episodic memory, after process-based training, has been observed in both young and older adults although this area is under debate. This work has primarily involved healthy adults and whether the same findings apply to those with ABI needs to be investigated.

This research study aims to develop and evaluate a novel treatment intervention for people with ABI that combines a process-based cognitive training with a strategy-based GMT rehabilitation intervention, and to acquire functional magnetic resonance imaging (fMRI) data before and after the intervention to measure patterns of brain activity associated with a task requiring executive functions. We propose that outcomes from GMT might be improved by an adaptive, process-based intervention aimed at enhancing working memory processes. Adaptive task difficulty involves dynamic adjustment of training task demands so that the individual remains within an optimal range of performance.

i. Aims

The primary aim of the study is to investigate whether it is feasible and acceptable to deliver a novel intervention combining GMT with WMU training, within a randomised controlled trial (RCT) context in a sample of ABI individuals. A further aim is to examine the behavioural and neural changes related to the novel intervention as well as the effect sizes.

ii. Research Question

This project will combine methods from neuropsychological rehabilitation and cognitive neuroscience to answer the following: 1) Is it feasible to combine an existing treatment for executive dysfunction, GMT, with an adaptive WMU training and how much benefit is gained? 2) Does the novel treatment combination promote neural plasticity that is detectable using fMRI?

iii. Outcomes

Primary outcomes will be measures of feasibility, acceptability, and fidelity.

Secondary outcomes will be pre- to post-training change in behavioural data (i.e., neuro-psychological assessment battery, measures of cognitive task performance and everyday functioning) and fMRI data (i.e., task-related brain activity), analysed by training condition. In addition, exploratory analyses of individual differences in responsiveness to WMU training will be performed, by calculating correlations between amount of adaptive training task improvement and pre- to post-training change on neural, cognitive, and functional measurements.

iv. Design

Randomised controlled trial methodology; specifically stratified randomisation in conjunction with permuted block random allocation, using an active control group will compare two conditions: (1) GMT combined with adaptive training \[AT\]; (2) GMT combined with non-adaptive \[NA\] training. Thirty-two adults with non-progressive ABI sustained in adulthood will be recruited from the NHS.. Participants will complete a combination of standard GMT (9 sessions) and 8 WMU (AT or NA) training sessions, delivered in small groups. Neuropsychological and functional assessments will be performed before and after the intervention. In addition, fMRI scanning sessions will be conducted pre- and post-training

Eligibility criteria: Inclusion Criteria:

* Only those able to give informed consent and able to comply with the training protocol will be included.
* ≥ 6 months post-ABI at time of recruitment (expression of interest to participate either verbally or in writing)
* Adults over the age of 18.
* English language fluency (speaking)
* a combination of self/relative/friend/carer reports of everyday organisation/memory problems

Exclusion Criteria:

* Individuals with contra-indications to MRI (e.g. heart pacemaker)
* Comorbid progressive neurological disorder or neurodegenerative condition (e.g. dementia)
* Major psychiatric disorder considered likely to prevent engagement in the intervention programme (pre-ABI history of mood disorder or stable antidepressant medication will not lead to exclusion)
* History of major substance abuse problems likely to prevent engagement in the intervention programme
* Unable to give informed consent
* Unable to cooperate with the study protocol (e.g. severe impairment of hearing, vision or language)

Primary outcomes:
measure: Feasibility of Recruitment Process.
timeFrame: From pre-intervention (Week 1) to post-intervention (Week 12).
measure: Participants' Drop-out Rates
timeFrame: From pre-intervention (Week 1) to post-intervention (Week 12).
measure: Participants' Coherence and Adherence to the Intervention.
timeFrame: From pre-intervention (Week 1) to post-intervention (Week 12).
measure: Feedback Questionnaire
timeFrame: Post-intervention session (Week 12)
Secondary outcomes:
measure: Visuospatial Working Memory Using the Visuospatial Matrix Updating fMRI Task
timeFrame: Post-intervention session (week 12)
measure: Visuospatial Working Memory fMRI Task Accuracy Using the Spatial N-back fMRI Task
timeFrame: Post-intervention session (Week 12)
measure: Episodic Visual Memory Accuracy Using the Object-location Association fMRI Task.
timeFrame: Post-intervention session (Week 12)
measure: Changes in Shifting Attention Using the Intra-Extra Dimensional Set Shift Test Variant From CANTAB Connect Research Web-testing.
timeFrame: Pre-intervention (Week 1) and post-intervention (Week 12)
measure: Changes in Spatial Planning and Problem Solving Using the Stockings of Cambridge Test Variant From CANTAB Connect Research Web-testing.
timeFrame: Pre-intervention (Week 1) and post-intervention (Week 12)
measure: Changes in Spatial Working Memory Using the Spatial Working Memory Test Variant From CANTAB Connect Research Web-testing.
timeFrame: Pre-intervention (Week 1) and post-intervention (Week 12)
measure: Changes in Visuospatial Working Memory Using the Spatial Span Forward Test Variant From CANTAB Connect Research Web-testing.
timeFrame: Pre-intervention (Week 1) and post-intervention (Week 12)
measure: Changes in Visuospatial Working Memory Using the Spatial Span Reverse Test Variant From CANTAB Connect Research Web-testing.
timeFrame: Pre-intervention (Week 1) and Post-intervention (Week 12)
Other outcomes:
Locations:
city: Carluke
country: United Kingdom
facility: Lead Communirty Brain Injury Team NHS Lanarkshire Law House Airdrie Road
state: Lanarkshire
Study officials:
affiliation: University of Glasgow
name: Jonathan Evans, PhD, DClin
role: PRINCIPAL_INVESTIGATOR
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