Clinical trial NCT04975685: Strengthening Mental Abilities With Relational Training (SMART) in Multiple Sclerosis (MS): A Feasibility Trial
Official title: Strengthening Mental Abilities With Relational Training (SMART) in Multiple Sclerosis (MS): A Feasibility Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: University of Lincoln
Sponsor class: OTHER
Collaborators: name: University of Exeter
name: Nottinghamshire Healthcare NHS Trust
name: National University of Ireland, Maynooth
name: University of Nottingham
First posted: 2021-07-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Background: Multiple Sclerosis (MS) is a chronic condition of the central nervous system; around 1 in 600 people in the United Kingdom have MS. Many people with MS (70%) have cognitive difficulties, which they experience as distressing and disabling, and there is currently a lack of treatment options to improve these difficulties.

SMART (Strengthening Mental Abilities with Relational Training) - a theory-based online cognitive training programme, which has been shown to improve general cognitive abilities - has not been tested with people who have MS.

Aims: To conduct a feasibility study to inform development of a definitive trial of SMART for improving cognitive functioning in people with MS. The investigators will assess:

1. Acceptability to participants of the intervention, delivery format, inclusion/exclusion criteria, baseline and outcome measures, randomisation protocol, and study procedures
2. The framework for a cost-effectiveness analysis alongside a definitive trial
3. Participant recruitment and retention rates
4. Sample-size needed for fully powered trial
5. Signal of efficacy

Plan: To address Aims 1-5, the investigators will recruit 60 adults with MS who are experiencing cognitive difficulties, identified from MS clinics.

Participants will complete baseline assessments of their cognitive abilities and answer questionnaires about their cognitive difficulties, personal priorities, mood, fatigue, self-efficacy, quality of life, and healthcare services used.

Assessments will be administered by a researcher, face-to-face or remotely.

Participants will be randomly allocated to one of three arms (20 per group):

Group 1: Receives SMART intervention online - plus usual care (MS Nurse support). SMART intervention involves completing a series of logic problems, which are designed to train skills that scaffold complex cognition.

Group 2: Receives usual care alone. Group 3: Receives a 'control' intervention online - plus usual care.

Baseline measures will be re-administered at three- and six-months post-randomisation. Researchers and patient-partners (people with personal experience of MS, who will act as co-researchers) will also interview 30 participants about their experience of the study and treatment. All qualitative data will be transcribed and thematically analysed in terms of a priori feasibility aims. Quantitative data will enable sample-size calculation for a definitive study and determine signal of efficacy.

Detailed description: Background:

Cognitive deficits have been identified as the most debilitating impact of MS. These deficits interfere with daily living, manifesting as inattention (e.g., getting easily distracted), forgetting (e.g., leaving the stove on after cooking), and problem-solving difficulties (e.g., getting confused when completing a multi-stage task like cooking). The burden of these deficits reduces quality of life and restricts daily activities and employment - and correspondingly, diminishes patient perceptions of personal competence and self-worth. Cognitive rehabilitation is not routinely offered in the National Health Service (NHS) - and, when it is offered, largely focuses on teaching people to compensate for deficits (e.g., using external memory aids) rather than retraining cognitive skills. A recent state-of-the-field review from international MS experts has called for research towards identifying effective, evidence-based, and clinically feasible interventions to address cognitive deficits in MS. There is evident uncertainty about how to intervene effectively, and this is recognised by the James Lind Alliance as a top-10 priority area for research-funding.

Our trial tests the feasibility of a highly accessible and low-resource format of cognitive rehabilitation (online training). Given NHS resource constraints, the scale of the problem, and concerns about face-to-face consultation in the context of COVID-19, new and cost-effective ways of implementing promising cognitive rehabilitation interventions are needed. Low-resource online formats are more likely to be implemented if found to be clinically effective, enable wider access for patients, and provide active support for self-management - consistent with (1) models of care for managing longer-term conditions and (2) the digital healthcare agenda.

As a feasibility trial, outcomes are unlikely to immediately effect changes to NHS practice. However, this is a necessary step towards developing a definitive trial - and will give us a signal of efficacy, a prerequisite for progression to a definitive trial. If found to be clinically- and cost-effective, the latter trial could create a step-change in MS cognitive rehabilitation - improving service-delivery and optimising support with limited additional resources.

Aim:

To conduct a feasibility study to inform development of a definitive trial of SMART (an online 'brain training' treatment) for improving cognitive functioning in people with MS.

The investigators will assess:

1. Acceptability to participants of the intervention, delivery format, inclusion/exclusion criteria, baseline and outcome measures, randomisation protocol, and study procedures
2. The framework for a cost-effectiveness analysis alongside a definitive trial
3. Participant recruitment and retention rates
4. Sample-size needed for fully powered trial
5. Signal of efficacy

Research plan:

The investigators will conduct a three-arm feasibility Randomised Controlled Trial (RCT) comparing (1) SMART + treatment-as-usual (TAU) with (2) TAU and (3) active control ('sham') training + TAU.

Consenting eligible patients will complete a baseline cognitive assessment battery and questionnaires assessing impact of living with MS, health-related quality of life, subjective cognitive difficulties, and service/resource-use.

After completing baseline assessments, participants will be randomly allocated to one of three arms (using minimisation to balance participant characteristics across arms):

1. SMART + TAU
2. TAU. Content of TAU for cognitive concerns, based on our clinical experience and knowledge, is often informational support from an MS Nurse with signposting to the MS Society/MS Trust websites.
3. Sham training (active control: Sudoku) + TAU. The investigators selected Sudoku to control for expectancy effects based on popular conceptions that it broadly improves cognitive functions, coupled with little evidence supporting this notion, and its use as an active control in similar trials. Sham-training will be delivered online, over the same timeframe/regimen as SMART treatment, and with telephone support to facilitate access - controlling for modality, schedule of engagement, and relational support.

A Research Fellow will complete blinded outcomes at 3- and 6-months post-randomisation, by re-administering baseline measures. Quantitative data will enable sample-size calculation for a definitive study and determine signal of efficacy. After the first follow-up assessment (\>3 months post-randomisation) a sub-sample of participants will engage in feasibility-feedback interviews.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of MS, received ≥3-months pre-enrolment (allowing for acute adjustment, as per other trials of cognitive rehabilitation)
* Age 18-89 (to meet the standardisation criteria of psychometric assessments)
* Cognitive difficulties as assessed by Perceived Deficits Questionnaire (PDQ) self-report (≥27) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) testing (≤1 standard deviation below normative reference-value)
* Able to read and speak English to standard necessary for completing assessment and intervention procedures
* Able and willing to access a computer/tablet/smart-phone with internet connection throughout the study
* Able and willing to give informed consent

Exclusion Criteria:

* Currently receiving cognitive rehabilitation
* Previously received SMART training
* Vision or hearing problems precluding completion of procedures

Primary outcomes:
measure: Recruitment and retention rates
timeFrame: 16 months
measure: Completion rates of outcome measures
timeFrame: 6 months
measure: Intervention drop-out rate
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
measure: Perceived Deficits Questionnaire (PDQ)
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: Symbol Digit Modalities Test (SDMT)
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: Generalized Anxiety Disorder Scale-7 (GAD-7)
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: Modified Fatigue Impact Scale-5-Item (MFIS-5)
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: Personal Questionnaire (PQ)
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: EQ-5D-5L
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: MS Impact Scale-29 (MSIS-29)
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
measure: ICECAP-A
timeFrame: Change between baseline and 3-month follow-up. Additional follow-up at 6 months.
Locations:
city: Nottingham
country: United Kingdom
facility: Nottingham Centre for Multiple Sclerosis and Neuroinflammation
Study officials:
affiliation: University of Lincoln
name: Nima Moghaddam, DClinPsy
role: PRINCIPAL_INVESTIGATOR
References:
citation: Golijani-Moghaddam N, Dawson DL, Evangelou N, Turton J, Hawton A, Law GR, Roche B, Rowan E, Burge R, Frost AC, das Nair R. Strengthening Mental Abilities with Relational Training (SMART) in multiple sclerosis (MS): study protocol for a feasibility randomised controlled trial. Pilot Feasibility Stud. 2022 Sep 3;8(1):195. doi: 10.1186/s40814-022-01152-7.