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

Multiple Sclerosis Clinical Trial

— DBL  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06068582
• Other study ID #: NL82007.018.23
• Secondary ID: NWA.1292.19.064
• Status: Recruiting
• Phase: N/A
• Start date: April 16, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: October 2023
• Source: Amsterdam UMC, location VUmc
• Contact: Jip Aarts
• Phone: +31 71 5275081
• Email: j.aarts[@]fsw.leidenuniv.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 67 Years

Eligibility

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

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Multiple Sclerosis
• Sclerosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Centers, location VUmc	Amsterdam

Sponsors (7)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc	Genzyme, a Sanofi Company, Merck BV, MS Sherpa, MS Vereniging Nederland, Personal Fitness Nederland, Universiteit Leiden

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quality of Life	Quality of life assessed using the 36-item Short Form. Item-scores are summed and transformed into a total score that ranges 0-100. Higher score corresponds with better quality of life.	Baseline, Month 4, Month 10, and Month 16
Secondary	Information processing speed	Information processing speed is assessed using the Symbol Digit Modalities Test (SMDT). The total responses made in 90 seconds is administered. Higher amount of correct responses equals better information processing speed.	Baseline, Month 4, Month 10, and Month 16
Secondary	Information processing speed	Information processing speed is assessed using the Paced Auditory Serial Addition Test (PASAT). The total correct answers given, out of 60, is administered. Higher amount of correct responses equals better information processing speed.	Baseline, Month 4, Month 10, and Month 16
Secondary	Verbal fluency	Verbal fluency is assessed using the Dutch adaptation of the Controlled Oral Word Association Test; Dutch Letter Fluency Test. Total number of correct words will be administered. Higher score corresponds with better verbal fluency.	Baseline, Month 4, Month 10, and Month 16
Secondary	Spatial Processing	Spatial Processing is assessed using the Judgement of Line Orientation. Total correct responses, with maximum 30, will be administered. Higher score corresponds with better spatial processing.	Baseline, Month 4, Month 10, and Month 16
Secondary	Verbal New Learning and Memory	New Learning and Memory is assessed using the California Verbal Learning Test, second edition (CVLT-II). Direct recall on the CVLT-II will be administered using number of correctly remembered items over learning trials 1-5. Delayed recall on CVLT-II will be administered using number of correctly remembered items 20 minutes after learning trail 5. Maximum scores for direct recall, delayed recall, and recognition are set at 80, 16, and 44, respectively. Higher score equals better verbal learning and memory.	Baseline, Month 4, Month 10, and Month 16
Secondary	Visual New Learning and Memory	New Learning and Memory is assessed using the Brief Visuospatial Memory Test-Revised (BVMT-R). Direct recall on BVMT-R will be administered using number of correctly remembered items over learning trials 1-3. Delayed recall on BVMT-R will be administered using number of correctly remembered items 25 minutes after learning trail 3. Maximum scores for direct recall, delayed recall, and recognition are set at 36, 12, and 12, respectively. Higher score equals better visual learning and memory.	Baseline, Month 4, Month 10, and Month 16
Secondary	Executive Function	Executive Function is assessed using the Delis-Kaplan Executive Function System. Total correct sorts will be administered, with a maximum of 16 sorts. A higher score suggests better executive functioning.	Baseline, Month 4, Month 10, and Month 16
Secondary	Self-Reported Cognitive Functioning	Self-Reported Cognitive Functioning is assessed using the Multiple Sclerosis Neuropsychological Screening Questionnaire. Maximum score of 70 can be reached, with a score of 27 or higher indicating presence of neuropsychological problems.	Baseline, Month 4, Month 10, and Month 16
Secondary	Work Participation and Productivity	Work Participation and Productivity is assessed using the Work Productivity and Activity Impairment Questionnaire: General Health, which administers the effect of health-problems on ability to work. Scores are calculated as percentages, with higher numbers indicating greater impairment and less productivity.	Baseline, Month 4, Month 10, and Month 16
Secondary	Work Difficulties	Work Difficulties are assessed using the Multiple Sclerosis Work Difficulties Questionnaire. The questionnaire consists of 23 items, which can be grouped into three subscales: psychological/cognitive barriers, physical barriers, and external barriers. The maximum score of each subscale is 100, with higher scores indicating higher perceived difficulties. Total score consists of an average of the three subscale scores.	Baseline, Month 4, Month 10, and Month 16
Secondary	Capability to carry out Work Activities	Capability to carry out Work Activities is assessed using the Capability Set for Work Questionnaire. This questionnaire evaluates for seven valued work aspects whether, A) it is important to the worker, B) their work offers sufficient opportunities to do it, and C) it can be achieved, on a 5-point Likert scale.	Baseline, Month 4, Month 10, and Month 16
Secondary	Quality of Working Life	Quality of Working Life is assessed using the Quality of Working Life Questionnaire for Cancer Survivors. The questionnaire consists of five subscales: meaning of work, perception of the work situation, atmosphere in the work environment, understandings and recognition in the organisation, and problems due to health situation. The overall score and sum scores of the subscales are calculated with a standardised score 0-100. Higher score corresponds with better quality of working life.	Baseline, Month 4, Month 10, and Month 16
Secondary	Grey Matter Volume of the Brain	Grey Matter Volume will be determined using FSL-SIENAX, after lesion filling on the 3DTI.	Baseline, Month 4, and Month 16
Secondary	White Matter Volume of the Brain	White Matter Volume will be determined using FSL-SIENAX, after lesion filling on the 3DTI.	Baseline, Month 4, and Month 16
Secondary	Total Brain Volume	Total Brain Volume will be determined using FSL-SIENAX, after lesion filling on the 3DTI.	Baseline, Month 4, and Month 16
Secondary	Volumes of Deep Grey Matter Structures	Volumes of Deep Grey Matter Structures will be determined using FIRST.	Baseline, Month 4, and Month 16
Secondary	Cortical Thickness	Cortical Thickness will be determined using Freesurfer.	Baseline, Month 4, and Month 16
Secondary	White Matter Integrity	White Matter Integrity will be determined using Diffusion Tensor Imaging	Baseline, Month 4, and Month 16
Secondary	Functional Connectivity	Functional Connectivity will be determined using Resting-State fMRI	Baseline, Month 4, and Month 16
Secondary	Regional Functional Activation	Regional Functional Activation will be determined using Task-Based fMRI	Baseline, Month 4, and Month 16
Secondary	Fatigue	Fatigue will be assessed using the Checklist Individual Strength. The questionnaire consists of 20 items, scored on a 7-point Likert scale. Fatigue is a subscale of the questionnaire, and is scored by adding the scores of the items, where a higher score corresponds with more fatigue.	Baseline, Month 4, Month 10, and Month 16
Secondary	Mood and Anxiety	Mood and Anxiety will be assessed using the Hospital Anxiety and Depression Scale. The questionnaire consists of 14 items on a 4-point Likert scale. The range of scores is 0-21 where a higher score equals more complaints of anxiety and depression.	Baseline, Month 4, Month 10, and Month 16
Secondary	Resilience	Resilience will be assessed using the Connor Davidson Resilience Scale. Total score ranges 0-100, with higher scores reflecting greater resilience.	Baseline, Month 4, Month 10, and Month 16
Secondary	Perceived Level of Stress	Perceived Level of Stress will be assessed using the Perceived Stress Scale. Total score ranges 0-40, with higher scores indicating higher perceived stress.	Baseline, Month 4, Month 10, and Month 16
Secondary	Social Mindfulness	Social Mindfulness will be assessed using the SoMi paradigm by van Doesum et al. (2013). Choices that are made are scores as mindful (1) or unmindful (0). Final score will be computed by averaging the scores over all decisions, resulting in a number between 0 (unmindful) and 1 (mindful).	Baseline, Month 4, Month 10, and Month 16
Secondary	Social Participation	Social Participation will be assessed using the PROMIS 'Ability to Participate in Social Roles and Activities' item bank. The questionnaire consists of eight items that can be scored on a 5-point Likert scale. Higher scores indicate better ability to participate in social roles and activities.	Baseline, Month 4, Month 10, and Month 16
Secondary	MS-related disability	MS-related disability will be assessed using the Expanded Disability Status Scale. This scale ranges from 0.0 to 10.0, where a higher score indicates worse disability.	Baseline, Month 4, Month 10, and Month 16
Secondary	Balance	Balance will be assessed using the Mini-BESTest. The test contains 14 items where a total score of 28 points can be achieved, where a score <19 induces an increased risk of falling.	Baseline, Month 4, and Month 16
Secondary	Walking Speed	Walking Speed will be assessed using the Timed 25-Foot Walk.	Baseline, Month 4, and Month 16
Secondary	Endurance	Endurance will be assessed using the Shuttle Walk Test according to the protocol of Singh et al. (1992).	Baseline, Month 4, and Month 16
Secondary	Grip Strength	Grip Strength will be assessed using a JAMAR hand-held dynamometer.	Baseline, Month 4, and Month 16
Secondary	Upper Limb Dexterity	Upper Limb Dexterity will be assessed using the 9-Hole Peg Test and the Purdue Pegboard Test.	Baseline, Month 4, and Month 16
Secondary	Lost Productivity Costs	Lost Productivity Costs will be assessed using the iMTA Productivity Cost Questionnaire. The questionnaire consists of three modules measuring absenteeism, presenteeism, and productivity loss from unpaid work.	Baseline, Month 4, Month 10, and Month 16
Secondary	Societal Costs including Healthcare, Patient, and family	Societal Costs will be assessed using the iMTA Medical Consumption Questionnaire.	Baseline, Month 4, Month 10, and Month 16
Secondary	Quality Adjusted Life Years	Quality Adjusted Life Years will be assessed using the EuroQol five-dimensional Questionnaire. The questionnaire comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Higher scores indicate more problems considering the dimensions.	Baseline, Month 4, Month 10, and Month 16