<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03759249</url>
  </required_header>
  <id_info>
    <org_study_id>SLEEPFAMS</org_study_id>
    <nct_id>NCT03759249</nct_id>
  </id_info>
  <brief_title>Sleep Medical Treatment in MS Patients Suffering From Fatigue</brief_title>
  <acronym>Sleep-in-MS</acronym>
  <official_title>Control Fatigue: Sleep Medical Treatment as a Novel Therapeutic Approach to an Unmet Medical Need in Multiple Sclerosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Charite University, Berlin, Germany</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Genzyme, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Charite University, Berlin, Germany</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the effect of an extensive sleep medical investigation and of the&#xD;
      subsequent treatment on multiple sclerosis (MS) related fatigue (provided a previously&#xD;
      unknown sleep disorder was found).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fatigue is among the most frequent symptoms in multiple sclerosis (MS) patients with&#xD;
      substantial negative impact on quality of life and employment status; one third of patients&#xD;
      describe fatigue as their most burdensome symptom. The enormous personal and socioeconomic&#xD;
      burden of this symptom is in striking contrast to the limited therapeutic options.&#xD;
&#xD;
      In a previous polysomnographic study, we found a strong association between sleep disorders&#xD;
      and fatigue in MS, measured with the Modified Fatigue Impact Scale (MFIS) and the&#xD;
      Fatigue-Severity-Scale (FSS). Thus, it is conceivable that a consequent treatment of sleep&#xD;
      disorders may improve fatigue, at least in a subset of patients which would yield a great&#xD;
      benefit as pharmacological treatment options for fatigue are insufficient.&#xD;
&#xD;
      All consecutive MS patients of our outpatient clinic will be screened for fatigue. In case of&#xD;
      fatigue (MFIS values &gt; 34) or signs of sleep disorders (Pittsburgh sleep quality index &gt; 5)&#xD;
      the MS patients were invited to participate in the study. All MS patients will be interviewed&#xD;
      by a sleep specialist, and will fill out questionnaires. Afterwards, they will be&#xD;
      investigated by two consecutive polysomnographies in the sleep laboratory, followed (if&#xD;
      necessary) by multiple sleep latencies tests. Subsequently, a sleep medical diagnosis will be&#xD;
      established (no sleep disorder or sleep apnea or insomnia or restless legs syndrome or any&#xD;
      other sleep disorders according to the International Classification of Sleep disorders 3th&#xD;
      ed.). The primary endpoint will be the Modified Fatigue Impact Scale (MFIS) value six months&#xD;
      after sleep medical treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Recruitment number could not be reached, difficult conditions under Corona&#xD;
  </why_stopped>
  <start_date type="Actual">December 8, 2015</start_date>
  <completion_date type="Actual">May 31, 2021</completion_date>
  <primary_completion_date type="Actual">May 31, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Modified Fatigue Impact Scale value</measure>
    <time_frame>six months after treatment</time_frame>
    <description>Measuring fatigue&#xD;
Total value of the Modified Fatigue Impact Scale: 0-84 (min-max), higher values represent increased fatigue, and lower values are considered to be a better outcome</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Multiple Sclerosis</condition>
  <condition>Fatigue</condition>
  <arm_group>
    <arm_group_label>Treatment group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Standard Treatment of Sleep disorder according to applicable guideline</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Waiting list</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Continuation of former treatment, after completing the study standard treatment of Sleep disorder according to applicable guidelines</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sleep medical treatment</intervention_name>
    <description>The participant ungo Standard Sleep medical diagnostics. If a sleep disorder is diagnosed in the interventional Group the applicable therapy is conducted.&#xD;
If the participant is randomized in the waiting Group the applicable Therapy is initiated after study completion.</description>
    <arm_group_label>Treatment group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  multiple sclerosis&#xD;
&#xD;
          -  fatigue&#xD;
&#xD;
          -  MFIS values greater than 34 or Pittsburgh Sleep Quality Index greater than 5&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Expanded disability status scale greater than 5&#xD;
&#xD;
          -  relapse in the last four weeks&#xD;
&#xD;
          -  immunosuppressants in the last two years&#xD;
&#xD;
          -  therapy with positive airway pressure (CPAP or BIPAP/ASV)&#xD;
&#xD;
          -  treatment with opioids&#xD;
&#xD;
          -  treatment with oestrogen&#xD;
&#xD;
          -  body mass index greater than 40&#xD;
&#xD;
          -  depression (beck depression inventory (BDI) values greater 20; in case of treatment&#xD;
             with antidepressants BDI values greater than 12 or suicidal ideas)&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  anaemia (hemoglobine &lt; 11,5 g/dl in women and &lt; 12,5 g/dl in men)&#xD;
&#xD;
          -  thyroid-stimulating hormone outside the normal range&#xD;
&#xD;
          -  renal insufficiency (creatinine clearance &lt; 75ml/min)&#xD;
&#xD;
          -  elevated transaminases (tripled)&#xD;
&#xD;
          -  chronic heart failure (NYHA II, III or IV)&#xD;
&#xD;
          -  respiratory insufficiency (CO2 &gt; 45 mmHg or pO2 &lt; 60 mmHg (capillary or arterial) or&#xD;
             long-term oxygen therapy)&#xD;
&#xD;
          -  carcinoma in the medical history (except for curative approach without relapse in the&#xD;
             last 10 years)&#xD;
&#xD;
          -  chemotherapy&#xD;
&#xD;
          -  poorly controlled diabetes (Glycated hemoglobin greater than 8 per cent)&#xD;
&#xD;
          -  pituitary adenomas&#xD;
&#xD;
          -  diabetes insipidus&#xD;
&#xD;
          -  fibromyalgia&#xD;
&#xD;
          -  unclear weight loss greater than 12 kg in one year&#xD;
&#xD;
          -  myasthenia gravis or any neuromuscular disorder&#xD;
&#xD;
          -  ulcerating colitis or Crohn's disease&#xD;
&#xD;
          -  AIDS or infection with HIV&#xD;
&#xD;
          -  acute infection in the last two months&#xD;
&#xD;
          -  stroke or apoplexy in the history&#xD;
&#xD;
          -  Parkinson's Disease&#xD;
&#xD;
          -  substance or drug abuse&#xD;
&#xD;
          -  participation in other interventional trials&#xD;
&#xD;
          -  capacity for consent is lacking&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Friedemann Paul, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Charite University, Berlin, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Charité University Medicine Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <reference>
    <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>
    <PMID>27904656</PMID>
  </reference>
  <reference>
    <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>
    <PMID>21652611</PMID>
  </reference>
  <reference>
    <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>
    <PMID>23764040</PMID>
  </reference>
  <reference>
    <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>
    <PMID>21278050</PMID>
  </reference>
  <reference>
    <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>
    <PMID>22183937</PMID>
  </reference>
  <reference>
    <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.</citation>
    <PMID>22914848</PMID>
  </reference>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>November 28, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>July 28, 2021</last_update_submitted>
  <last_update_submitted_qc>July 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Charite University, Berlin, Germany</investigator_affiliation>
    <investigator_full_name>Friedemann Paul</investigator_full_name>
    <investigator_title>Prof. Dr. Friedemann Paul</investigator_title>
  </responsible_party>
  <keyword>multiple sclerosis</keyword>
  <keyword>polysomnography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
    <mesh_term>Fatigue</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03759249
org study id: SLEEPFAMS
nct id: NCT03759249
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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).
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Modified Fatigue Impact Scale value
time frame: six months after treatment
description: Measuring fatigue
Total value of the Modified Fatigue Impact Scale: 0-84 (min-max), higher values represent increased fatigue, and lower values are considered to be a better outcome
arm group label: Treatment group
arm group type: Experimental
description: Standard Treatment of Sleep disorder according to applicable guideline
arm group label: Waiting list
arm group type: No Intervention
description: Continuation of former treatment, after completing the study standard treatment of Sleep disorder according to applicable guidelines
intervention type: Other
intervention name: Sleep medical treatment
description: The participant ungo Standard Sleep medical diagnostics. If a sleep disorder is diagnosed in the interventional Group the applicable therapy is conducted.
If the participant is randomized in the waiting Group the applicable Therapy is initiated after study completion.
arm group label: Treatment group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Friedemann Paul, MD
role: Principal Investigator
affiliation: Charite University, Berlin, Germany
facility: 
country: Germany
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.
PMID: 27904656
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.
PMID: 21652611
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.
PMID: 23764040
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.
PMID: 21278050
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.
PMID: 22183937
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.
PMID: 22914848
responsible party type: Principal Investigator
investigator affiliation: Charite University, Berlin, Germany
investigator full name: Friedemann Paul
investigator title: Prof. Dr. Friedemann Paul
mesh term: Multiple Sclerosis
mesh term: Sclerosis
mesh term: Fatigue
sharing ipd: No