Multidimensional Assessment of Fatigue in Multiple Sclerosis- Observational Study - Ticino

Study Overview
=================
Brief Summary
-----------------
Fatigue is a common symptom in patients with multiple sclerosis, however, its nature is not completely understood. Fatigue overlaps often with other symptoms such as somnolence, depression and cognitive disorders, from which it is not always readily distinguished. The evaluation of fatigue and the three most frequently associated symptoms using a multidimensional approach might allow to understand, which methodology is the best indicated to estimate the prevalence of fatigue with greatest accuracy, leading to a better differentiation of the symptoms in the diagnostic setting.

Detailed Description
-----------------
Objectives: 1- to provide a detailed characterization of fatigue in a cohort of selected MS patients, including a definition of the boundaries and the overlaps between fatigue, somnolence, mood disorders and attention dysfunction; 2- to see how the prevalence and the overlaps between fatigue, somnolence, depression and attention dysfunction are influenced by the method of assessment. 3-To better characterize the sleep structure in MS patients with fatigue under both the macro- and microstructural point of view.

Official Title
-----------------
Multidimensional Assessment of Fatigue in Multiple Sclerosis- Observational Study - Ticino

Conditions
-----------------
Multiple Sclerosis

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Definite diagnosis of MS (14,15) or CIS (16);according to the most recent standard criteria Expanded Disability Status Scale (EDSS) score < 7.0 (17); Last magnetic resonance imaging (MRI) within the previous 12 months; Male or female; >18 years old; Willing to perform the study procedures; Signed Informed consent. Exclusion Criteria: Mini Mental Status Examination (MMSE) score < 24; Relapse within the last 3 months; Radiologically isolated syndrome (RIS); History of drug and/or alcohol abuse; Any serious general medical condition like decompensated cardiopulmonary disease, cancer or decompensated renal failure, as well as any neurological condition (other than MS) that can interfere with the correct execution of the study design.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MS-Group<br>MS-Group | |
| Healthy control<br>Healthy control | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue Severity Scale | a self-administered 9-items scale. The patient gives a score from 1 to 7 to each item. The resulting score is given as the mean value. Subjects with a score higher that 4 are considered fatigued. This scale assesses the impact of fatigue on multiple outcomes, with a physical focus. FSS has been validated for MS, it has an acceptable internal consistency, it is a reliable, completely safe and brief scale, which in addition has been shown to follow clinical changes in fatigue perception over time. Furthermore, FSS scores correlate with other commonly used fatigue scales, like the Modified Fatigue Impact Scale | 1 Day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Fatigue Impact Scale | a 21-items scale, which was proposed by the MS Council for Clinical Practice Guidelines as a shortened version of the previous 40-items Fatigue Impact Scale (21). The patient gives a score from 0 to 4 at each item, to express how every item best describes the personal experience, where 0 is never and 4 is almost always; the final score is the sum of the 21 items. The cut-off score beyond whom the subject can be considered fatigued is 38. The administration time is approximately 5-10 minutes. The MFIS is a structured, reliable, self-report questionnaire that the patient can generally complete easily, with little or no intervention from an interviewer. It provides a multidimensional assessment of fatigue, considering its impact on physical (9 items), cognitive (10 items) and phychosocial (2 items) functioning in daily life. It has a good reproducibility and a strong correlation with FSS results | 1 Day | 
| Fatigue Scale for Motor and Cognitive functions | a validated questionnaire specifically developed for MS (22). It is a 20-items scales that allows graduation of fatigue severity, and separate evaluation of motor (10 items) and cognitive (10 items) fatigue components. The response pattern for each item consists in a five-point Likert scale; a total score higher than 43 indicates the presence of mild fatigue and the score increases proportionally to the severity of fatigue (> 53: moderate; >63 severe); the cut-off for both the cognitive and the motor subscales is 22. FSMC provides good reliability and correlates with both FSS and MFIS scores | 1 Day | 
| Visual analogue scale for fatigue | a simple and quick measure of the patient's instant perception of fatigue on him/herself. It is a measurement of the impression at the moment of the interview. It consists of a graphic 10 cm wide line with no fatigue at one end and very severe fatigue on the other and the subject is asked to place a cross at the point that best express his/her answer to the question how do you feel in this moment? | 1 Day | 
| Maintenance of wakefulness test | it objectively explores somnolence in terms of ability to remain awake in sleep- promoting environmental conditions. It has to be performed after a nocturnal PSG recording because the knowledge of the previous sleep is essential for MWT interpretation. Recordings include only EEG, EMG and EOG from the previous PSG and are carried out in a dim room, with slight illumination. Patients are instructed to stay awake as long as possible. Four sessions are recorded every two hours, each lasting until the patient falls asleep or for 40 minutes of continuous awake state. The sleep latency is assessed in each of the four recordings and it is defined by the elapse time in minutes on each trial before sleep onset: the patient is considered asleep after three 30 seconds EEG epochs of stage N1 of non-REM sleep, or one 30-second epoch of any other sleep stage. | 1 Day | 
| Epworth Sleepiness Scale | a self-administered questionnaire with 8 questions, which provide a measure of a subject's general level of daytime sleepiness (26). Subjects are required to indicate their chance to fall asleep in 8 different situations on a rating scale from 0 to 3, where 0 means no chance and 3 big chance. The total score is the sum of the eight items, and a score higher that 10 suggests an excessive daytime sleepiness, whose severity increases proportionally to the score. Most people can answer the questions with no assistance in less than 5 minutes. | 1 Day | 
| Visual analogue scale for somnolence | a simple and quick measure of the patient's instant perception of somnolence on him/herself. It is a measurement of the impression at the moment of the interview. It consists of a graphic 10 cm wide line with no sleepiness at one end and very severe sleepiness on the other and the subject is asked to place a cross at the point that best express his/her answer to the question how do you feel in this moment?. | 1 Day | 
| Beck depression inventory II | a 21-item self-report of depressive symptomatology for individuals aged 13 to 80 years (32). It was developed to have clinical sensitivity for assessing depression criteria reported in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) and intends to assess symptoms experienced in the 2 weeks prior to assessment, such as intense sadness, crying, or changes in sleep, appetite, or sexual interest. Items are on a 4-point scale ranging from 0 to 3, with a maximum score of 63. Higher total scores indicate more severe depression symptoms. Administration of the scale takes about 10 minutes. | 1 Day | 
| Mongomery Asberg Depression Rating Scale | is a 10-items questionnaire that is used to measure the core symptoms and cognitive features of clinical depression (33). An higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. The subject has to be interviewed by a trained psychologist or psychiatrist. | 1 Day | 
| Symbol Digit Modalities Test | is a measure of attention and processing speed. It presents a series of nine symbols, each of which is paired with a single digit, labelled 1-9, in a key at the top of a sheet. The remainder of the page has a pseudorandomized sequence of the symbols and the subject must respond with the digit associated with each of these as quickly as possible. The score is the number of correct answers in 90 seconds. | 1 Day | 
| Paced Auditory Serial Addition Test | is another measure of sustained attention and speed of information processing. The subject hears a series of single digit number from CD that are presented at the rate of one every 3 seconds in the first part of the test (PASAT 3), or at the rate of one every 2 seconds in the second part (PASAT 2). The subject is asked to add each consecutive digit to the one immediately preceding it. Sixty-one digits are presented for each part and each part has a maximum of 60 correct answers. | 1 Day | 
| Stroop Test | evaluates sustained attention and some aspects of executive functions, such as the ability to elaborate relevant and irrelevant dimensions in parallel and to inhibit an automatic response while performing a task based on conflicting stimuli. The procedure comprised of three trials. In the first trial, the subject is instructed to read a list of word indicating colours printed in black ink as quickly as possible; in the second trial the subject is instructed to name the colour of strings of dots as quickly as possible; in the third trial (interference condition), the subject has to name the colours of the ink of words indicating conflicting colours as quickly as possible. Performance will assess by calculating the time required to name the items and the number of the errors. | 1 Day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Somnolence, Multiple scerlosis, Fatigue, Sleep, Depression, Cognitive disorders