Clinical trial NCT03759249: Sleep Medical Treatment in MS Patients Suffering From Fatigue
Official title: Control Fatigue: Sleep Medical Treatment as a Novel Therapeutic Approach to an Unmet Medical Need in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Multiple Sclerosis
Fatigue
Keywords: multiple sclerosis
polysomnography
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2018-11-29
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the effect of an extensive sleep medical investigation and of the subsequent treatment on multiple sclerosis (MS) related fatigue (provided a previously unknown sleep disorder was found).

Detailed description: Fatigue is among the most frequent symptoms in multiple sclerosis (MS) patients with substantial negative impact on quality of life and employment status; one third of patients describe fatigue as their most burdensome symptom. The enormous personal and socioeconomic burden of this symptom is in striking contrast to the limited therapeutic options.

In a previous polysomnographic study, we found a strong association between sleep disorders and fatigue in MS, measured with the Modified Fatigue Impact Scale (MFIS) and the Fatigue-Severity-Scale (FSS). Thus, it is conceivable that a consequent treatment of sleep disorders may improve fatigue, at least in a subset of patients which would yield a great benefit as pharmacological treatment options for fatigue are insufficient.

All consecutive MS patients of our outpatient clinic will be screened for fatigue. In case of fatigue (MFIS values \> 34) or signs of sleep disorders (Pittsburgh sleep quality index \> 5) the MS patients were invited to participate in the study. All MS patients will be interviewed by a sleep specialist, and will fill out questionnaires. Afterwards, they will be investigated by two consecutive polysomnographies in the sleep laboratory, followed (if necessary) by multiple sleep latencies tests. Subsequently, a sleep medical diagnosis will be established (no sleep disorder or sleep apnea or insomnia or restless legs syndrome or any other sleep disorders according to the International Classification of Sleep disorders 3th ed.). The primary endpoint will be the Modified Fatigue Impact Scale (MFIS) value six months after sleep medical treatment.

Eligibility criteria: Inclusion Criteria:

* multiple sclerosis
* fatigue
* MFIS values greater than 34 or Pittsburgh Sleep Quality Index greater than 5

Exclusion Criteria:

* Expanded disability status scale greater than 5
* relapse in the last four weeks
* immunosuppressants in the last two years
* therapy with positive airway pressure (CPAP or BIPAP/ASV)
* treatment with opioids
* treatment with oestrogen
* body mass index greater than 40
* depression (beck depression inventory (BDI) values greater 20; in case of treatment with antidepressants BDI values greater than 12 or suicidal ideas)
* pregnancy
* anaemia (hemoglobine \< 11,5 g/dl in women and \< 12,5 g/dl in men)
* thyroid-stimulating hormone outside the normal range
* renal insufficiency (creatinine clearance \< 75ml/min)
* elevated transaminases (tripled)
* chronic heart failure (NYHA II, III or IV)
* respiratory insufficiency (CO2 \> 45 mmHg or pO2 \< 60 mmHg (capillary or arterial) or long-term oxygen therapy)
* carcinoma in the medical history (except for curative approach without relapse in the last 10 years)
* chemotherapy
* poorly controlled diabetes (Glycated hemoglobin greater than 8 per cent)
* pituitary adenomas
* diabetes insipidus
* fibromyalgia
* unclear weight loss greater than 12 kg in one year
* myasthenia gravis or any neuromuscular disorder
* ulcerating colitis or Crohn's disease
* AIDS or infection with HIV
* acute infection in the last two months
* stroke or apoplexy in the history
* Parkinson's Disease
* substance or drug abuse
* participation in other interventional trials
* capacity for consent is lacking

Primary outcomes:
measure: Modified Fatigue Impact Scale value
timeFrame: six months after treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité University Medicine Berlin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Friedemann Paul, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Veauthier C, Hasselmann H, Gold SM, Paul F. The Berlin Treatment Algorithm: recommendations for tailored innovative therapeutic strategies for multiple sclerosis-related fatigue. EPMA J. 2016 Nov 24;7(1):25. doi: 10.1186/s13167-016-0073-3. eCollection 2016.
citation: Veauthier C, Paul F. Fatigue in multiple sclerosis: which patient should be referred to a sleep specialist? Mult Scler. 2012 Feb;18(2):248-9. doi: 10.1177/1352458511411229. Epub 2011 Jun 7. No abstract available.
citation: Veauthier C, Gaede G, Radbruch H, Gottschalk S, Wernecke KD, Paul F. Treatment of sleep disorders may improve fatigue in multiple sclerosis. Clin Neurol Neurosurg. 2013 Sep;115(9):1826-30. doi: 10.1016/j.clineuro.2013.05.018. Epub 2013 Jun 12.
citation: Veauthier C, Radbruch H, Gaede G, Pfueller CF, Dorr J, Bellmann-Strobl J, Wernecke KD, Zipp F, Paul F, Sieb JP. Fatigue in multiple sclerosis is closely related to sleep disorders: a polysomnographic cross-sectional study. Mult Scler. 2011 May;17(5):613-22. doi: 10.1177/1352458510393772. Epub 2011 Jan 28.
citation: Kaminska M, Kimoff RJ, Benedetti A, Robinson A, Bar-Or A, Lapierre Y, Schwartzman K, Trojan DA. Obstructive sleep apnea is associated with fatigue in multiple sclerosis. Mult Scler. 2012 Aug;18(8):1159-69. doi: 10.1177/1352458511432328. Epub 2011 Dec 19.
citation: Cote I, Trojan DA, Kaminska M, Cardoso M, Benedetti A, Weiss D, Robinson A, Bar-Or A, Lapierre Y, Kimoff RJ. Impact of sleep disorder treatment on fatigue in multiple sclerosis. Mult Scler. 2013 Apr;19(4):480-9. doi: 10.1177/1352458512455958. Epub 2012 Aug 22.