Clinical trial NCT06068582: Don't be Late! Postponing Cognitive Decline and Preventing Early Unemployment in People With Multiple Sclerosis
Official title: Don't be Late! Postponing Cognitive Decline and Preventing Early Unemployment in People With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Cognition
Exercise
Employment
Prevention
Health-related Quality of Life
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
Collaborators: name: Universiteit Leiden
name: Personal Fitness Nederland
name: MS Vereniging Nederland
name: Merck BV
name: Genzyme, a Sanofi Company
name: MS Sherpa
First posted: 2023-10-05
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 67
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Quality of Life
timeFrame: Baseline, Month 4, Month 10, and Month 16
Secondary outcomes:
measure: Information processing speed
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Information processing speed
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Verbal fluency
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Spatial Processing
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Verbal New Learning and Memory
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Visual New Learning and Memory
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Executive Function
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Self-Reported Cognitive Functioning
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Work Participation and Productivity
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Work Difficulties
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Capability to carry out Work Activities
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Quality of Working Life
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Grey Matter Volume of the Brain
timeFrame: Baseline, Month 4, and Month 16
measure: White Matter Volume of the Brain
timeFrame: Baseline, Month 4, and Month 16
measure: Total Brain Volume
timeFrame: Baseline, Month 4, and Month 16
measure: Volumes of Deep Grey Matter Structures
timeFrame: Baseline, Month 4, and Month 16
measure: Cortical Thickness
timeFrame: Baseline, Month 4, and Month 16
measure: White Matter Integrity
timeFrame: Baseline, Month 4, and Month 16
measure: Functional Connectivity
timeFrame: Baseline, Month 4, and Month 16
measure: Regional Functional Activation
timeFrame: Baseline, Month 4, and Month 16
measure: Fatigue
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Mood and Anxiety
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Resilience
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Perceived Level of Stress
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Social Mindfulness
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Social Participation
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: MS-related disability
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Balance
timeFrame: Baseline, Month 4, and Month 16
measure: Walking Speed
timeFrame: Baseline, Month 4, and Month 16
measure: Endurance
timeFrame: Baseline, Month 4, and Month 16
measure: Grip Strength
timeFrame: Baseline, Month 4, and Month 16
measure: Upper Limb Dexterity
timeFrame: Baseline, Month 4, and Month 16
measure: Lost Productivity Costs
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Societal Costs including Healthcare, Patient, and family
timeFrame: Baseline, Month 4, Month 10, and Month 16
measure: Quality Adjusted Life Years
timeFrame: Baseline, Month 4, Month 10, and Month 16
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centers, location VUmc
Study officials:
affiliation: Leiden University
name: Hanneke E Hulst
role: PRINCIPAL_INVESTIGATOR
References: