Cognitive Performance, Sleep Disturbances and Fatigue in Multiple Sclerosis

NCT07426991 | Recruiting

• 1 other identifier: 2024-2957
• Study Type: observational
• Target: 837
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Multiple Sclerosis; Remitting-Relapsing Multiple Sclerosis; Primary Progressive Multiple Sclerosis; Secondary Progress Multiple Sclerosis; Fatigue Syndrome, Chronic; Sleep Disorders

Keywords

MS; Sleep; Fatigue; Cognition

Outcome Measures

Primary Outcomes (7)

• Severity of Fatigue (subjective fatigue)

  Fatigue Scale for Motor and Cognitive Functions (FSMC) * Higher score = Higher fatigue * Min. score: 11 * Max. score: 100

  Baseline and Follow-up (12-18 Months after Baseline)

• Severity of Fatigue (cognitive fatigability)

  Alertness subtest of the Test Battery of Attention (TAP) * Measurement of reaction time * Normalized for age and education * Administered pre- and posttest

  Baseline and Follow-up (12-18 Months after Baseline)

• Severity of Fatigue (physical fatigability)

  Hand-grip-strength dynamometer \- Measurement of grip strength

  Baseline and Follow-up (12-18 Months after Baseline)

• Sleep disorders according to AASM criteria

  Diagnostics by medical personnel after 2 nights of polysomnographic measurements.

  Baseline and Follow-up (12-18 Months after Baseline)

• Verbal Learning and Memory Test (VLMT)

  Assesses verbal learning, immediate and delayed recall, and recognition of word lists, commonly used to evaluate verbal memory performance.

  Baseline and Follow-up (12-18 Months after Baseline)

• Symbol Digit Modalities Test (SDMT)

  Evaluates information processing speed, attention, and visual scanning by requiring rapid symbol-number substitutions.

  Baseline and Follow-up (12-18 Months after Baseline)

• Brief Visuospatial Memory Test - Revised (BVMT-R)

  Measures visuospatial learning and memory through repeated recall of geometric figures, including delayed recall and recognition.

  Baseline and Follow-up (12-18 Months after Baseline)

Secondary Outcomes (22)

• Pittsburgh Sleep Quality Index (PSQI)

  Baseline and Follow-up (12-18 Months after Baseline)

• Epworth Sleepiness Scale (ESS)

  Baseline and Follow-up (12-18 Months after Baseline)

• Stanford Sleepiness Scale (SSS)

  Baseline and Follow-up (12-18 Months after Baseline)

• Insomnia Severity Index (ISI-G)

  Baseline and Follow-up (12-18 Months after Baseline)

• International RLS Study Group Rating Scale (IRLS)

  Baseline and Follow-up (12-18 Months after Baseline)

Study Arms (2)

Multiple Sclerosis

* Diagnosis of MS according to the 2017 revised McDonald criteria * 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) * Age ≥ 18 and ≤ 79 years * Adequate (corrected) hearing and vision to complete neuropsychological testing * Sufficient proficiency in German to participate in assessments * Capacity to provide informed consent and understanding of study procedures

Other: No Intervention: Observational Cohort

Control group

* Indication for sleep medicine evaluation * Age ≥ 18 and ≤ 79 years * Adequate (corrected) hearing and vision to complete neuropsychological testing * Sufficient proficiency in German to participate in assessments * Capacity to provide informed consent and understanding of study procedures

Other: No Intervention: Observational Cohort

Interventions

No Intervention: Observational Cohort OTHER

No intervention: observational cohort

Control group; Multiple Sclerosis

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be consecutively recruited at both study centers: the Department of Neurology at the University Hospital Düsseldorf and Kliniken Maria Hilf, Mönchengladbach. This collaboration combines the sleep medicine expertise of Kliniken Maria Hilf with the MS care expertise of University Hospital Düsseldorf, thereby providing optimal conditions to address the study objectives. Recruitment will additionally be supported by local neurologists in the Mönchengladbach region, who will establish initial contact between potential participants and the study centers. Informed consent will continue to be obtained by the study team.

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead
• Maria Hilf Clinics GmbH, Mönchengladbach: collaborator
• Roche Pharma AG: collaborator
• German Multiple Sclerosis Society: collaborator

Study Sites (2)

University Hospital Düsseldorf

Düsseldorf, 40223, Germany

RECRUITING

Maria Hilf Clinics

Mönchengladbach, 41063, Germany

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Fatigue Syndrome, Chronic; Sleep Wake Disorders; Fatigue

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Neuromuscular Diseases; Neurologic Manifestations; Signs and Symptoms; Mental Disorders

Central Study Contacts

Carolin Balloff, Dr. rer. nat.

CONTACT

+4917622970340; carolin.balloff@gmail.com

Philipp Albrecht, Prof. Dr. med.

CONTACT

phil.albrecht@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: February 23, 2026
• Study Start: November 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 6, 2026

Record last verified: 2025-11

Locations

DE (2)