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

NCT ID: NCT06068582

Last Updated: 2025-04-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 270 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-16
• Study Completion Date: 2026-09-30

Brief Summary

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Strengthening the brain

Participants receive 30 minutes of 1-on-1 fitness training, dietary advice, and mental coaching, in addition to twice 20 minutes fitness at home, and 60 minutes of cognitive training each week for four months.

Group Type: EXPERIMENTAL

Strenghtening the brain

Intervention Type: BEHAVIORAL

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.

Strengthening the mind

Partiicpants receive biweekly 1-on-1 coaching by a trained work-coach who has MS to identify challenges at work and implement solutions. It is completed when satisfactory solutions have been implemented for all challenges or after four months.

Group Type: EXPERIMENTAL

Strengthening the mind

Intervention Type: BEHAVIORAL

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.

Enhanced usual care

Participants receiving general information about cognitive impairment in MS and following care as usual for four months.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 67 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universiteit Leiden

OTHER

Sponsor Role: collaborator

Personal Fitness Nederland

UNKNOWN

Sponsor Role: collaborator

MS Vereniging Nederland

UNKNOWN

Sponsor Role: collaborator

Merck BV

UNKNOWN

Sponsor Role: collaborator

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: collaborator

MS Sherpa

UNKNOWN

Sponsor Role: collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: lead

Responsible Party

Hanneke Hulst

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hanneke E Hulst

Role: PRINCIPAL_INVESTIGATOR

Leiden University

Locations

Amsterdam University Medical Centers, location VUmc

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Jip Aarts

Role: CONTACT

j.aarts@fsw.leidenuniv.nl

+31 71 5275081

Shalina Saddal

Role: CONTACT

s.saddal@amsterdamumc.nl

+31 20 566 38 01

References

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(1):28. doi: 10.1186/s12883-023-03513-y.

Reference Type: DERIVED

PMID: 38225561 (View on PubMed)

Other Identifiers

NWA.1292.19.064

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

NL82007.018.23

Identifier Type: -

Identifier Source: org_study_id