Don't be Late! Postponing Cognitive Decline and Preventing Early Unemployment in People With Multiple Sclerosis

Overview

The goal of this randomized controlled trial is to compare the effectiveness of two innovative interventions aimed at preventing cognitive decline and work-related problems to enhanced usual care in improving quality of life in people with multiple sclerosis. Secondary objectives are: * to compare the effectiveness of the investigated interventions in improving cognitive, psychological, and work functioning, and in enhancing the brain's functional network * to examine which factors (i.e., baseline cognitive, psychological, work, and brain MRI-parameters) are predictive of the response to the investigated interventions * aim to qualitatively reflect on the process and outcome of the investigated interventions considering the perspectives of relevant stakeholders to allow for smooth and successful implementation in clinical practice Participants will follow the intervention for four months, with follow-up measurements at six months after intervention and 12 months after intervention.

Detailed description

Background Up to 65% of the people with multiple sclerosis (PwMS) develop cognitive deficits that severely affect daily life functioning and PwMS' quality of life. Moreover, approximately 65% of all patients end up unemployed within five years after diagnosis. Current treatments mostly focus on symptom management and return to work, which may be too late. It is hypothesized that timely interventions will help prevent or delay cognitive decline and work-related problems in PwMS, thereby improving quality of life.

Objectives

Primary Objective:

To compare the effectiveness of the investigated interventions with enhanced usual care in improving quality of life.

Secondary Objectives:

1. To compare the effectiveness of the investigated interventions in improving cognitive, psychological and work functioning, and in enhancing the brain's functional network. 2. To examine which factors (i.e. baseline cognitive, psychological, work and brain MRI-parameters) are predictive of the response to the investigated interventions. 3. To qualitatively reflect on the process and outcome of the investigated interventions considering the perspectives of relevant stakeholders to allow for smooth and successful implementation in clinical practice. 4. To compare the cost-effectiveness of the investigated interventions.

Material and methods A randomized controlled trial with three arms and three follow-up visits over a total time period of 16 months. During these visits researchers will gather information from questionnaires, neuropsychological examination, MRI and blood sampling. All participants (N= 240) have a confirmed MS diagnosis according to the McDonald 2017 criteria, have subclinical cognitive impairment and are aged between 18 and 67. Participants will be randomly assigned to one of the three arms (N=90 in each arm). Interviews will be conducted with 12-15 participants from both interventions, 10-12 sport coaches, 8-12 work coaches and 10-12 supervisors from the workplace.

'Strengthening the brain' (4 month-program) consists of weekly 30 minutes 1-on-1 exercise and lifestyle coaching in combination with two moments per week unsupervised exercises at home and a home-based online computerized cognitive training. 'Strengthening the mind' (4 month-program) consists of biweekly contact with work coaches who are all diagnosed with MS themselves. 'Enhanced usual care' entails an appointment with a researcher in addition to usual care.

Results The primary outcome is change in quality of life as measured with the 36-item Short Form. Several secondary outcomes will be collected: cognitive, psychological, cost-effectiveness, structural- and functional brain, neurological, physiological, and qualitative measures.

Interventions

• Behavioral Strenghtening the brain
  Lifestyle intervention containing physical exercise, lifestyle coaching, and cognitive training. The programme contains weekly 30 minutes 1-on-1 fitness and lifestyle coaching with two moments of exercise at home for 20 minutes. Online computerized cognitive training will be done for 60 minutes per week.
• Behavioral Strengthening the mind
  Work-focused intervention combining the capability approach and the participatory approach. Together with a work-coach who has been diagnosed with MS themselves, participants will assess important work values, discover challenges participants are facing, think of solutions for these challenges, develop a plan of action and implement these solutions.

Primary outcome measures

• Quality of Life [Time frame: Baseline, Month 4, Month 10, and Month 16]

Secondary outcome measures (12)

• Information processing speed [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Information processing speed [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Verbal fluency [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Spatial Processing [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Verbal New Learning and Memory [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Visual New Learning and Memory [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Executive Function [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Self-Reported Cognitive Functioning [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Work Participation and Productivity [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Work Difficulties [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Capability to carry out Work Activities [Time frame: Baseline, Month 4, Month 10, and Month 16]
• Quality of Working Life [Time frame: Baseline, Month 4, Month 10, and Month 16]

Eligibility criteria

Inclusion criteria

• Confirmed MS diagnosis according to the McDonald 2017 criteria
• Age between 18 and 67
• No changes in disease modifying therapy prior to inclusion (i.e., no changes in last 3 months) - this criterion only applies at inclusion to ensure participants are in a stable situation at the start of the study and for follow-up measures, changes in treatment will be registered but will not result in exclusion from the study
• no current relapse or steroid treatment in the six weeks prior to study visits
• presence of mild cognitive deficits (at least one test with a Z-score of -1.0 to -1.99 below norm scores of healthy controls on the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery
• being able to participate in an exercise intervention (i.e., EDSS < 6.0)
• fulfilling safety criteria for MRI (no metal inside body, not pregnant, no claustrophobia)

Exclusion criteria

• presence of neurological (other than MS) and psychiatric disorders
• a current or history of drug or alcohol abuse
• being unable to speak or read Dutch
• currently on sick leave for a period of 6 weeks or longer
• currently pregnant

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Prevention

Study locations

Netherlands · 1 center

• Amsterdam University Medical Centers, location VUmc — Amsterdam

Publications

• Aarts J, Saddal SRD, Bosmans JE, de Groot V, de Jong BA, Klein M, Ruitenberg MFL, Schaafsma FG, Schippers ECF, Schoonheim MM, Uitdehaag BMJ, van der Veen S, Waskowiak PT, Widdershoven GAM, van der Hiele K, Hulst HE; Don't be late! consortium. Don't be late! Postponing cognitive decline and preventing early unemployment in people with multiple sclerosis: a study protocol. BMC Neurol. 2024 Jan 15;24 PMID 38225561

Identifiers

NCT: NCT06068582 · NL82007.018.23 · NWA.1292.19.064

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗