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Trial registered on ANZCTR


Registration number
ACTRN12617000808347
Ethics application status
Approved
Date submitted
26/05/2017
Date registered
2/06/2017
Date last updated
28/01/2020
Date data sharing statement initially provided
6/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
COMBAT-MS (COgnitive reMediation and Behavioural Approaches to Treatment in Multiple Sclerosis)
Scientific title
COMBAT-MS (COgnitive reMediation and Behavioural Approaches to Treatment in Multiple Sclerosis)
Secondary ID [1] 292062 0
Nil known.
Universal Trial Number (UTN)
Trial acronym
COMBAT-MS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 303469 0
Condition category
Condition code
Neurological 302876 302876 0 0
Multiple sclerosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised, controlled, single-blinded, prospective, longitudinal study to assess psychosocial adjustment, learning and memory in patients with multiple sclerosis treated with a novel therapy combining CBT and Cognitive Remediation. Participants will be randomly assigned to receive either the study intervention for 10 weeks or assigned to receive treatment as usual (usual clinical care by their treating neurologist). Participants across both groups will receive assessments at baseline (prior to study intervention), immediate and long-term follow up. Assessors blinded to participant randomisation will conduct the immediate (3 month) and long-term (12 month) follow up assessments.

The study intervention will combine elements of an evidence-based CBT program targeting adjustment in MS (saMS) with evidence-based cognitive-training techniques involving both strategy training and computer-based cognitive training. The cognitive remediation component will be informed by the Neuropsychological Educational Approach to Remediation (NEAR).

The delivery of the study intervention will be lead by a Clinical Neuropsychologist with 8+ years of experience in neuropsychological and psychological assessment and the delivery of CBT and cognitive remediation. The intervention will be delivered in a group-based therapy format for two hours a week over one session for 10 weeks. The intervention will be delivered in a university research centre. The therapy will be delivered in small groups of 6-10 people. The content will be shown on slides and presented by the trial psychologists. The format of the sessions will generally follow the following sequence: 1) presentation of psychoeducational content relating to MS, mood, anxiety, stress, and cognition; 2) discussion of how the content relates to the individuals in the group; 3) teaching of strategies to assist with difficulties with mood, anxiety, stress, and cognition; 3) practicing those strategies with a partner from the group.

For participants located >40km from the study centre, they will be offered the opportunity to participate in the group intervention remotely via video conferencing.

Patients enrolled in the study will receive a participant information statement. They will be asked to complete self-report questionnaires assessing factors associated with psychosocial adjustment. During the intervention, they will receive psychoeducational content in the form of print out of slides. They will be able to refer to this content whenever they wish.The trial psychologists will use a battery of neuropsychological measures from the MACFIMS battery to assess patients. Trial neurologists will utilise the Expanded Disability Status Scale to assess disability in trial participants.

We aim to determine whether this program has an impact on psychological factors (i.e. depression, anxiety, stress, coping, self-efficacy, health related quality of life and productivity) and aspects of cognitive functioning (i.e. memory, attention, speed of information processing, executive functions, visuospatial skills) contributing to adjustment. In a randomized controlled design, this will be achieved by administering standardised psychological and neuropsychological assessments pre and post intervention that have been shown to be sensitive in persons with MS. Sustainability of effects will be monitored by repeating these assessments at a 12-month follow-up visit. We also aim to determine whether the program is associated with secondary benefits to pharmacological treatment adherence and disease course (e.g. number of relapses; severity of physical symptoms).

A register of attendance at each session will be used to monitor adherence.
Intervention code [1] 298194 0
Treatment: Other
Intervention code [2] 298231 0
Behaviour
Comparator / control treatment
Participants will be randomly assigned to receive either the study intervention for 10 weeks or assigned to receive treatment as usual (usual clinical care by their treating neurologist).
Control group
Active

Outcomes
Primary outcome [1] 302266 0
A primary objective of this research is to explore whether a combined Cognitive Behaviour Therapy (CBT) and Cognitive Remediation program benefits psychosocial adjustment in patients with MS, assessed using the SF-36.
Timepoint [1] 302266 0
At baseline and 3 and 12 months post commencement of intervention.
Primary outcome [2] 302316 0
A primary objective of this research is to explore whether a combined Cognitive Behaviour Therapy (CBT) and Cognitive Remediation program benefits learning in patients with MS, assessed using the CVLT-II and BVMT-R.
Timepoint [2] 302316 0
At baseline and 3 and 12 months post commencement of intervention.
Primary outcome [3] 302317 0
A primary objective of this research is to explore whether a combined Cognitive Behaviour Therapy (CBT) and Cognitive Remediation program benefits memory in patients with MS, assessed using the CVLT-II and BVMT-R.
Timepoint [3] 302317 0
At baseline and 3 and 12 months post commencement of intervention.
Secondary outcome [1] 335318 0
A secondary objective is to explore whether the program is associated with benefits to general cognition, assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery.
Timepoint [1] 335318 0
At baseline and 3 and 12 months post commencement of intervention.
Secondary outcome [2] 335450 0
A secondary objective is to explore whether the program is associated with benefits to subjective cognitive impairment, assessed using the MSNQ-P, MSNQ-I and Perceived Deficits Questionnaire.
Timepoint [2] 335450 0
At baseline and 3 and 12 months post commencement of intervention.
Secondary outcome [3] 335451 0
A secondary objective is to explore whether the program is associated with benefits to physical impairments, assessed using the MSQLI.
Timepoint [3] 335451 0
At baseline and 3 and 12 months post commencement of intervention.
Secondary outcome [4] 335453 0
A secondary objective is to explore whether the program is associated with benefits to coping strategies, assessed using the Psychological Vulnerability Scale and Ways of Coping Questionnaire.
Timepoint [4] 335453 0
At baseline and 3 and 12 months post commencement of intervention.
Secondary outcome [5] 335454 0
A secondary objective is to explore whether the program is associated with benefits to social and vocational support, assessed using the Work and Social Adjustment Scale and MOS Modified Social Support Scale.
Timepoint [5] 335454 0
At baseline and 3 and 12 months post commencement of intervention.
Secondary outcome [6] 335455 0
A secondary objective is to explore whether the program is associated with benefits to neurological disability, as measured by the Expanded Disability Status Scale.
Timepoint [6] 335455 0
At baseline and 3 and 12 months post commencement of intervention.
Secondary outcome [7] 335456 0
A secondary objective is to explore whether the program is associated with benefits to mental well-being, as measured by the Beck Depression Inventory-Fast Screen, Mental Health Inventory, and Perceived Stress Scale.
Timepoint [7] 335456 0
At baseline and 3 and 12 months post commencement of intervention.

Eligibility
Key inclusion criteria
1. Patient diagnosed with MS according to McDonald criteria
2. Aged 18 years or over
3. EDSS score between 0 – 8
4. Be willing and able to comply with study requirements for the duration of the trial
5. Have provided informed consent prior to study participation
6. None of the exclusion criteria
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Have a diagnosis of another neurodegenerative disease
2. Currently receiving other research-based study treatments in any form (e.g. receiving group or individual CBT, ACT, cognitive remediation or cognitive training)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
One group receiving treatment. One group not receiving treatment.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Mixed ANOVAs will be used to test for differences between treatment and control groups on study measures. Sociodemographic characteristics will be described at baseline. Descriptive statistics will include number of participants (N), mean, standard deviation, minimum, maximum and if a non- normal distribution, the median and first/third quartiles will be reported.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 296594 0
Commercial sector/Industry
Name [1] 296594 0
Novartis Australia
Address [1] 296594 0
Novartis Pharmaceuticals Australia
54 Waterloo Rd
Macquarie Park NSW 2113
Country [1] 296594 0
Australia
Primary sponsor type
University
Name
University of Sydney
Address
The University of Sydney
NSW 2006
Australia
Country
Australia
Secondary sponsor category [1] 295547 0
None
Name [1] 295547 0
Address [1] 295547 0
Country [1] 295547 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297821 0
Human Research Ethics Committees - The University of Sydney
Ethics committee address [1] 297821 0
Ethics and Research Integrity
Margaret Telfer Building (K07)
University of Sydney
NSW 2006
Ethics committee country [1] 297821 0
Australia
Date submitted for ethics approval [1] 297821 0
31/10/2016
Approval date [1] 297821 0
14/12/2016
Ethics approval number [1] 297821 0
2016/935

Summary
Brief summary
The COMBAT-MS study will determine the efficacy of a novel, world first management strategy for patients with MS involving combined cognitive remediation and cognitive behavioural therapy. The purpose of combining these techniques will be to create a novel holistic program that; (i) teaches individuals to engage in cognitively stimulating activities that aim to reduce the impact of and/or improve cognitive deficits, optimize day-to-day functioning, and have the capacity to build cognitive reserve and promote neuroplasticity, alongside techniques that; (ii) teach individuals to conceptualise problems as interactions between the person and environment. The COMBAT-MS study intervention will be delivered in a structured program over 3 months, with sustainability of effect tested to 12 months. Participants will be allocated to one of two groups: 1) a group that receives the study intervention, or 2) a group that does not receive the study intervention but receives standard clinical care as usual with their treating neurologist. All participants will be assessed at baseline, 3-month follow up and 12 month follow up. All participants will receive feedback on their results after each assessment.

In the initial 12-18 months, we aim to determine whether this program has an impact on psychological factors (i.e. depression, anxiety, stress, coping, self-efficacy, health related quality of life and productivity) and aspects of cognitive functioning (i.e. memory, attention, speed of information processing, executive functions, visuospatial skills) contributing to adjustment. In a randomized controlled design, this will be achieved by administering standardised psychological and neuropsychological assessments pre and post intervention that have been shown to be sensitive in persons with MS. We also aim to determine whether the program is associated with secondary benefits to pharmacological treatment adherence and disease course (e.g. number of relapses; severity of physical symptoms).
Trial website
Trial related presentations / publications
MS Innovations Conference - 2018
Public notes

Contacts
Principal investigator
Name 75186 0
A/Prof Michael Barnett
Address 75186 0
Sydney Neurology
Brain & Mind Centre, University of Sydney
Lvl 4, 94 Mallett Street,
Camperdown NSW 2050
Country 75186 0
Australia
Phone 75186 0
+61 2 9351 0730
Fax 75186 0
Email 75186 0
combat-ms.study@sydney.edu.au
Contact person for public queries
Name 75187 0
Dr Keri Diamond
Address 75187 0
MS Clinical Trials
Brain & Mind Centre, University of Sydney,
Lvl 5, 94 Mallett Street,
Camperdown NSW 2050
Country 75187 0
Australia
Phone 75187 0
+61 2 9351 0750
Fax 75187 0
Email 75187 0
combat-ms.study@sydney.edu.au
Contact person for scientific queries
Name 75188 0
Dr Keri Diamond
Address 75188 0
Sydney Neurology
Brain & Mind Centre, University of Sydney,
Lvl 4, 94 Mallett Street,
Camperdown NSW 2050
Country 75188 0
Australia
Phone 75188 0
+61 2 9351 0750
Fax 75188 0
Email 75188 0
combat-ms.study@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be available for this trial.
What supporting documents are/will be available?
No other documents available
Summary results
No Results