The MS-CEBA Study: Determining Cognitive, Energetic, Behavioural and Affective (CEBA) Profiles in Multiple Sclerosis

Study Overview
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Brief Summary
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Multiple Sclerosis (MS) is an invalidating neurological disease known to cause physical symptoms, which usually are the main focus of treatment. However, non-physical, more neuropsychological, symptoms also frequently occur, concerning the Cognitive, Energetic, Behavioural and Affective (CEBA) domains. Symptoms in the CEBA domains are known to negatively affect societal participation, and thereby quality of life. Unfortunately, despite their negative consequences, CEBA symptoms are not always timely recognized in people with MS (pwMS). Moreover, despite the fact that there are various effective neuropsychological treatments available for neurological patients with these symptoms, most pwMS do not yet receive these treatments. Although findings in group studies confirm that each of the CEBA domains can be affected in pwMS and correlations between symptoms regarding different CEBA domains have been found, there are large differences between individual pwMS with regard to which CEBA symptoms co-occur and which CEBA symptoms prevail. In order to optimize care for pwMS (e.g. timely referring patients to suiting neuropsychological treatment) there is need for a large scale study investigating over the whole range of CEBA symptoms how frequent these occur, whether and how symptoms co-occur, and thus if CEBA profiles can be identified. Identification of CEBA profiles can serve to quickly identify pwMS with neuropsychological problems in clinical practice, and provide an indication for possible neuropsychological treatment. If CEBA profiles are identified, it is considered likely that multiple CEBA symptoms will be prominent within a single CEBA profile. Here, subjective burden of pwMS can play an important role in determining which symptoms the main focus should be on in possible neuropsychological treatment. Currently, a clear and standardized procedure with a feasible neuropsychological screening instrument quickly identifying and combining CEBA profile and subjective burden, providing a suitable indication for possible neuropsychological treatment, is lacking. The aim of the present study is identifying CEBA profiles in pwMS and subsequently developing a feasible screening instrument allowing quick identification of CEBA profile and subjective burden of pwMS in clinical practice, providing a suitable indication for possible neuropsychological treatment. If needed, combining of or adjustments to existing neuropsychological treatments will be suggested in order meet the needs of pwMS with CEBA symptoms. All of this with the ultimate aim to improve societal participation, and accordingly quality of life, of pwMS.

Official Title
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The MS-CEBA Study: Determining Cognitive, Energetic, Behavioural and Affective (CEBA) Profiles in Multiple Sclerosis

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Other: There is no intervention.


Participation Criteria
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Eligibility Criteria
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In order to be eligible to participate in this study, a patient must meet all of the following criteria: Inclusion Criteria: Confirmed MS diagnosis (all subtypes); Age18-70; Adequate command of the Dutch language. Exclusion Criteria: Not being able to participate in a short neuropsychological assessment (NPA) as judged by the MS clinician and/or investigator; Presence of any other neurological and/or major psychiatric condition. The group of HC's will be matched to the patient group on age and education level.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Phase 1<br>In Phase 1 of the study, we aim to include a minimum of 300 patients to identify how often which CEBA symptoms occur among pwMS and which symptoms cluster together, forming CEBA profiles. In addition, in Phase 1, an on age and education level matched group of 100 Healthy controls will be included to allow comparison of performance-based measures. In Phase 2 of the study, we aim to include a minimum of 100 patients, after approximately two years, to investigate whether we can replicate the results of Phase 1, validating the different CEBA profiles. | Other: There is no intervention.<br>* There is no intervention.<br>|
| Retest Phase 1<br>After a year, a retest of around 50 patients will take place in order to determine whether CEBA symptoms are stable over time which is important information in deciding whether CEBA profiles can be used as a guide for further care. | Other: There is no intervention.<br>* There is no intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognition | The main study parameter is CEBA profile, which is latent and thus needs to be derived from the scores on neuropsychological tests and questionnaires regarding the CEBA domains, using latent profile analysis. Neuropsychological instruments regarding the Cognitive domain: Neuropsychological tests for information processing speed (Symbol Digit Modalities Test & Trail Making Test A) Neuropsychological tests for attentive/executive control (Trail Making Test A + B & Letterfluency) Neuropsychological tests for memory (15 Word Test & Digit Span Test of the Wechsler Adult Intelligence Scale) | 6-48 months | 
| Energy | The main study parameter is CEBA profile, which is latent and thus needs to be derived from the scores on neuropsychological tests and questionnaires regarding the CEBA domains, using latent profile analysis. Neuropsychological instrument regarding the Energetic domain: - Questionnaire for mental and physical fatigue (Dutch Multifactor Fatigue Scale) | 6-48 months | 
| Behaviour | The main study parameter is CEBA profile, which is latent and thus needs to be derived from the scores on neuropsychological tests and questionnaires regarding the CEBA domains, using latent profile analysis. Neuropsychological instruments regarding the Behavioural domain: Neuropsychological test for social cognition (Facial Expressions of Emotion - Stimuli and Tests) Subscales of a questionnaire for social cognitive symptoms (Dysexecutive Questionnaire - self and proxy) | 6-48 months | 
| Affect | The main study parameter is CEBA profile, which is latent and thus needs to be derived from the scores on neuropsychological tests and questionnaires regarding the CEBA domains, using latent profile analysis. Neuropsychological instrument regarding the Affective domain: - Questionnaire for anxiety and depression (Hospital Anxiety and Depression Scale) | 6-48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of societal participation | Level of societal participation will be derived from the score on a questionnaire called 'Impact on Participation and Autonomy (IPA)' | 6-48 months | 
| Subjective burden | Subjective burden will be obtained through conducting an anamnesis. | 6-48 months | 
| Demographic information | Demographic information will be derived from medical records and anamnesis. | 6-48 months |