Cognitive Performance, Sleep Disturbances and Fatigue in Multiple Sclerosis
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In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: No Intervention: Observational Cohort.
- Who it may be relevant to
- Registry conditions: Multiple Sclerosis, Remitting-Relapsing Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Secondary Progress Multiple Sclerosis. Basic parameters: 18 years — 79 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Germany
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
The Effects of Sleep Disturbances on Fatigue and Cognition in Multiple Sclerosis
Overview
Fatigue is a prevalent symptom in patients with multiple sclerosis (MS) and is associated with considerable impairment in quality of life as well as loss of occupational capacity. Sleep disturbances are regarded as a critical factor in the development of fatigue and are frequently observed in individuals with MS. However, they often remain underrecognized, undiagnosed, and consequently untreated. Polysomnography, the gold standard for assessing sleep architecture and quality, has rarely been applied in the investigation of sleep disorders in MS. Accordingly, uncertainties remain regarding the prevalence and extent to which sleep disturbances contribute to fatigue in this population. Moreover, emerging evidence suggests an association between sleep disorders and cognitive dysfunction in MS. Yet, it is unclear whether cognitive impairment arises from the sleep disorder itself, from the resulting fatigue, or from other independent factors. Pharmacological treatments for MS-related fatigue remain limited, given heterogeneous and frequently non-replicable effects. Non-pharmacological interventions such as physical activity, cognitive behavioral therapy, and psychoeducation have shown promise but yield variable outcomes. The development of novel and effective therapeutic strategies requires a more comprehensive understanding of the etiology of fatigue. To date, the role of sleep disturbances and their relationship to cognitive performance in MS have not been adequately investigated. The objective of this project is to determine the prevalence and characteristics of sleep disorders in MS patients with fatigue using polysomnography and to examine their relationship with cognitive impairment. In addition, the study will compare sleep quality parameters and the prevalence of sleep disorders across different MS subtypes (relapsing-remitting, primary progressive, and secondary progressive). Furthermore, within a sub-study, it will be investigated whether the type of immunotherapy has an influence on the aforementioned aspects. Finally, the project seeks to integrate artificial intelligence (AI) into polysomnography analysis to streamline data evaluation and facilitate the future assessment of therapeutic interventions. The study will be conducted as a non-invasive, non-interventional, longitudinal observational trial including MS patients with fatigue and a control group of patients with subjective sleep complaints but without MS. Recruitment will take place over 36 months at two centers: the Department of Neurology at the University Hospital Düsseldorf and the Maria Hilf Clinics in Mönchengladbach. Additional recruitment will be supported by community-based neurologists in the Mönchengladbach region to broaden the study cohort and ensure representativeness of the study population. Approximately 382 MS patients are expected to be enrolled. The number of control participants will be determined by the proportion of MS patients presenting with sleep disorders and will be recruited consecutively from the neurological sleep laboratory of the Maria Hilf Clinics. For AI training, retrospective polysomnography data from the past five years (N ≥ 10,000 patients) at the Maria Hilf Clinics will be utilized. The study protocol includes overnight polysomnography to assess sleep quality, along with comprehensive clinical evaluation, neuropsychological testing, and validated questionnaires addressing fatigue, subjective sleep quality, daytime sleepiness, depression, and anxiety. Based on manually scored polysomnography, AI models will be trained to identify key parameters of sleep quality. The findings of this study will advance the understanding of the role of sleep disturbances in MS-related fatigue and will facilitate the integration of AI into sleep research, thereby streamlining the evaluation of future therapeutic approaches.
Detailed description
1. Project Objectives
1.1. In-depth characterization of sleep disorders in MS patients with fatigue.
Exploratory analysis:
Which specific types of sleep disorders are most frequently observed in MS patients with fatigue?
1.2. Comparison of subjective fatigue severity and objectively measured fatigability between patients with and without abnormalities in sleep-related parameters.
Hypothesis:
Fatigue severity and fatigability differ significantly between MS patients with diagnosed sleep disorders and those without, with greater fatigue observed in patients with sleep disorders.
Exploratory analysis:
Which sleep-related parameters show the strongest correlation with fatigue severity and fatigability in MS patients?
1.3. Comparison of self-reported fatigue severity (FSMC) with fatigability as an objectively measurable, short-term phenomenon.
Hypothesis:
There is a significant association between self-reported fatigue severity and objectively measured fatigability, with higher subjective fatigue scores corresponding to greater motor and cognitive fatigability.
Exploratory analysis:
To what extent do discrepancies exist between subjective fatigue and objectively measured fatigability? Which moderating factors explain possible divergences between subjective perception and objective performance decline?
1.4. Comparison of fatigability between patients with and without abnormalities in sleep-related parameters.
Hypothesis:
Patients with sleep-related abnormalities demonstrate significantly greater objectively measured fatigability compared to patients without such abnormalities.
Exploratory analysis:
Which specific sleep-related parameters are associated with increased motor and/or cognitive fatigability? Do distinct patterns emerge for cognitive versus motor fatigability depending on the type of sleep disorder?
1.5. Comparison of cognitive performance between MS patients with and without abnormalities in sleep-related parameters.
Hypothesis:
Information processing speed as well as learning and memory performance are significantly reduced in MS patients with sleep disorders compared to those without.
Exploratory analysis:
Which specific sleep-related parameters are most strongly associated with cognitive impairments in MS patients?
1.6. Comparison of cognitive performance, subjective fatigue, and fatigability in MS patients with sleep disorders versus control patients without MS but with the same sleep disorders.
Hypothesis:
Information processing speed, learning, and memory performance are significantly lower in MS patients with sleep disorders compared to control individuals without MS who present with the same types of sleep disorders.
Hypothesis:
Fatigue severity and fatigability are significantly greater in MS patients with sleep disorders compared to control individuals without MS with the same types of sleep disorders.
Exploratory analysis:
What differences in the impact of sleep disorders on cognitive performance, fatigue, and fatigability can be identified between MS patients and control individuals without MS?
1.7. Comparison of sleep medicine parameters and prevalence of sleep disorders in patients with fatigue across different MS subtypes.
Exploratory analysis:
Are there significant differences in sleep-related parameters among MS patients with different disease courses?
Exploratory analysis:
Are there significant differences in the prevalence of sleep disorders among MS patients with different disease courses?
1.8. Investigation of longitudinal changes in objectively measured sleep parameters, fatigue, fatigability, and cognition over a 12-month period in patients with MS.
Exploratory analysis:
How do polysomnography-derived sleep parameters change in patients with MS over time?
Exploratory analysis:
Interventions
- Other No Intervention: Observational Cohort
No intervention: observational cohort
Primary outcome measures
- Severity of Fatigue (subjective fatigue) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Severity of Fatigue (cognitive fatigability) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Severity of Fatigue (physical fatigability) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Sleep disorders according to AASM criteria [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Verbal Learning and Memory Test (VLMT) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Symbol Digit Modalities Test (SDMT) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Brief Visuospatial Memory Test - Revised (BVMT-R) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
Secondary outcome measures (12)
- Pittsburgh Sleep Quality Index (PSQI) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Epworth Sleepiness Scale (ESS) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Stanford Sleepiness Scale (SSS) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Insomnia Severity Index (ISI-G) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- International RLS Study Group Rating Scale (IRLS) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Hospital Anxiety and Depression Scale (HADS) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Electroencephalogram (EEG) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Electromyogram (EMG) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Electrooculogram (EOG) [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Respiratory rate [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Nasal airflow [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
- Oxygen saturation [Time frame: Baseline and Follow-up (12-18 Months after Baseline)]
Eligibility criteria
Inclusion criteria
- Age ≥ 18 and ≤ 79 years (all groups)
- Adequate (corrected) hearing and vision to complete neuropsychological testing (all groups)
- Sufficient proficiency in German to participate in assessments (all groups)
- Capacity to provide informed consent and understanding of study procedures (all groups)
- Diagnosis of MS according to the 2017 revised McDonald criteria (MS group)
- Indication for sleep medicine evaluation due to at least mild fatigue, operationalized as ≥ 43 points on the Fatigue Scale for Motor and Cognitive Functions (FSMC) (MS group)
- Indication for sleep medicine evaluation (control group)
Exclusion criteria
- Lack of signed informed consent or inability to provide consent (all groups)
- Age < 18 years or > 79 years (all groups)
- Presence of another neurological disorder in addition to MS, with the exception of migraine (all groups)
- Use of medications that influence polysomnographic parameters (e.g., benzodiazepines) (all groups)
- Uncorrected hearing or vision impairment and/or insufficient German language proficiency likely to impact neuropsychological test results (all groups)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Cohort
Study locations
Germany · 2 centers
- University Hospital Düsseldorf — Düsseldorf
- Maria Hilf Clinics — Mönchengladbach
Identifiers
NCT: NCT07426991 · 2024-2957