xml: <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/NCT05992025</url>
    </required_header>
    <id_info>
      <org_study_id>2023-01455-01</org_study_id>
      <nct_id>NCT05992025</nct_id>
    </id_info>
    <brief_title>Digital Phenotyping and Lifestyle Intervention in Patients With Myasthenia Gravis</brief_title>
    <acronym>DIG-MG</acronym>
    <official_title>Randomized Controlled Trial: Digital Phenotyping and Lifestyle Intervention in Patients With Myasthenia Gravis to Reduce Fatigue</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Uppsala University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Uppsala University</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        Myasthenia Gravis (MG) is a chronic autoimmune neurological disorder where an antibody attack&#xD;
        of muscle receptors causes fatigable skeletal muscle weakness. In addition to fatigue,&#xD;
        several MG patients experience general fatigue. Small supervised studies during 12 weeks of&#xD;
        physical exercise interventions have indicated safety and beneficial neuromuscular outcomes&#xD;
        in MG patients. Longer and unsupervised studies are required to obtain guidelines for&#xD;
        physical activity in MG patients. Further, the development of smart rings enables remote&#xD;
        digital supervision of physical activity, sleep, and biological parameters such as heart&#xD;
        frequency, number of steps, and temperature. These parameters could add to the lack of&#xD;
        biomarkers in MG. The project design is a randomized controlled trial with a lifestyle&#xD;
        intervention to improve fatigue in the autoimmune neuromuscular disease Myasthenia Gravis&#xD;
        (MG). The intervention includes digital group counseling regarding physical activity, sleep,&#xD;
        general health, and digital follow-up with a &quot;smart ring&quot; (OURA).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The cohort is Myasthenia Gravis (MG) patients in Sweden. The primary research question is:&#xD;
        can digital lifestyle intervention in an online-group format improve fatigue as measured by&#xD;
        MG-ADL in MG patients by at least 30%? Secondary research question: can lifestyle&#xD;
        intervention improve fatigue as measured by FSS in MG by at least 30%?&#xD;
  &#xD;
        The primary outcome measure is MG-ADL; the secondary outcome measures include general fatigue&#xD;
        (fatigue severity scale and Chalder´s fatigue scale). Exploratory outcome measures include&#xD;
        OURA-ring-based markers, including heart rate variability, temperature fluctuations, and&#xD;
        sleep and activity parameters. These will be collected throughout the entire study period for&#xD;
        30 weeks.&#xD;
  &#xD;
        Analysis of serum biomarkers miR-150-5p and miR-30e-5p and inflammatory proteins found&#xD;
        upregulated in MG will be included. Clinical data at baseline: antibody status,&#xD;
        electrophysiology, MG Composite Scale (MGC), and clinical data at follow-up visits&#xD;
        (medications, MGC), etc., are extracted from the medical charts and the Swedish MG registry&#xD;
  &#xD;
        Inclusion criteria:&#xD;
  &#xD;
          -  An MG diagnosis for at least six months before entry into the study.&#xD;
  &#xD;
          -  Both patients with ocular and generalized MG are allowed to participate.&#xD;
  &#xD;
          -  For practical reasons, participants need to understand Swedish.&#xD;
  &#xD;
        Exclusion criteria:&#xD;
  &#xD;
          -  Participation in another clinical trial in the past 6 months.&#xD;
  &#xD;
          -  Disease duration less than 6 months.&#xD;
  &#xD;
          -  Contraindications to physical activity: unstable coronary syndrome or myocardial&#xD;
             infarction within the preceding three months, respiratory failure (vital capacity &lt; 70%&#xD;
             predicted value) or cardiac failure (ejection fraction &lt; 50% predicted value),&#xD;
             concomitant neuromuscular diseases, disabling rheumatological disease (&gt; 80% disability&#xD;
             on the Barthel scale), chronic pain or disabling orthopedic conditions, hospitalization&#xD;
             in the last three months for a serious medical or surgical condition, anemia (hematocrit&#xD;
             &lt; 30%), stroke within the previous year.&#xD;
  &#xD;
          -  MG patients already performing a moderate-intensity physical activity of 150min or more&#xD;
             per week, i.e., one of the target interventions.&#xD;
  &#xD;
          -  Pregnancy.&#xD;
  &#xD;
        Each participant is enrolled in the study for 7 months, and 26 persons are randomized to one&#xD;
        of the following 3 groups:&#xD;
  &#xD;
          -  Group 1; no intervention, observation with the OURA ring.&#xD;
  &#xD;
          -  Group 2: 12 weeks of physical activity guidance with short discussions via digital&#xD;
             meetings regularly. They will conduct at least 150 minutes per week of&#xD;
             moderate-intensity exercises. Brisk walks are the primary choice of activity;&#xD;
             alternatively, swimming, cycling, or dancing to the physical exertion according to the&#xD;
             Borg scale can be performed.&#xD;
  &#xD;
          -  Group 3: 12 weeks of sleep exercises. The lifestyle intervention of sleep will be&#xD;
             delivered via an online group, with recommended home practices between sessions. Topics&#xD;
             covered will include sleep education, sleep hygiene, and practices to improve sleep&#xD;
             quality.&#xD;
  &#xD;
        The study is digital and will use the platform &quot;minforskning.se&quot;, which is validated&#xD;
        according to GCP-GAMP5 and has the potential to collect digital consent forms.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 10, 2023</start_date>
    <completion_date type="Anticipated">July 2025</completion_date>
    <primary_completion_date type="Anticipated">January 2025</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>
      <intervention_model_description>Prospective, randomized controlled trial, parallel-group design</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>The statistician responsible for the outcome analysis will be blinded as to what intervention each group has had.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Myasthenia Gravis-Activities of Daily Living (MG-ADL)</measure>
      <time_frame>7 months</time_frame>
      <description>Subjective assessment of MG-related fatiguability. A person's score can range from zero (normal) to 24 (most severe).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Fatigue Severity Scale (FSS)</measure>
      <time_frame>7 months</time_frame>
      <description>The Fatigue Severity Scale (FSS) ranges from 0 (least fatigue) to 63 (maximum fatigue).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Chalder Fatigue Scale</measure>
      <time_frame>7 months</time_frame>
      <description>The Chalder Fatigue Scale ranges from 0 (least fatigue) to 33 (maximum fatigue)</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Heart rate variability</measure>
      <time_frame>7 months</time_frame>
      <description>Heart rate variability is measured with the OURA ring.</description>
    </other_outcome>
    <other_outcome>
      <measure>Activity pattern</measure>
      <time_frame>7 months</time_frame>
      <description>Number of steps and minutes in moderate and high intensity activity is measured by the OURA ring.</description>
    </other_outcome>
    <other_outcome>
      <measure>Percentage of deep sleep</measure>
      <time_frame>7 months</time_frame>
      <description>The OURA ring measures the sleep stages, including time and percentage for deep sleep every night.</description>
    </other_outcome>
    <other_outcome>
      <measure>Circulating miRNA in serum</measure>
      <time_frame>7 months</time_frame>
      <description>Changes in miR-150-5p and miR-30e-5p in serum samples.</description>
    </other_outcome>
    <other_outcome>
      <measure>Olink Target 96 Inflammation panel of cytokines</measure>
      <time_frame>7 months</time_frame>
      <description>Changes in cytokine NPX protein values (log2 scaled) using Proximity Extension Assay (PEA) technology in serum samples</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Myasthenia Gravis</condition>
    <arm_group>
      <arm_group_label>Observation</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Observation with the OURA ring and no digital meetings. The participants are offered delayed randomization after the study period. This group's outcome from the delayed randomization will be for the exploratory analysis, i.e., not in the primary analysis.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Physical activity</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>12 weeks of physical activity guidance with short discussions via online group meetings according to a schedule. The participants in this arm will conduct moderate-intensity exercises for at least 150 minutes per week. Brisk walks are the primary choice of activity; alternatively, swimming, cycling, or dancing to the physical exertion according to the Borg scale can be performed.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sleep hygiene intervention</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>12 weeks of sleep exercises. The lifestyle intervention of sleep will be delivered via an online group, with recommended home practices between sessions. Topics covered will include sleep education, sleep hygiene, and practices to improve sleep quality.</description>
    </arm_group>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Physical activity</intervention_name>
      <description>Intervention with physical activity more than 150 minutes of medium to high intensity per week.</description>
      <arm_group_label>Physical activity</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Behavioral</intervention_type>
      <intervention_name>Sleep hygiene</intervention_name>
      <description>Intervention with sleep hygiene to optimize sleep duration and quality.</description>
      <arm_group_label>Sleep hygiene intervention</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  The MG disease status must be stable for at least six months before entry into the&#xD;
               study; thus, the duration of the disease must be at least six months.&#xD;
  &#xD;
            -  Both patients with ocular and generalized MG are allowed to participate.&#xD;
  &#xD;
            -  For practical reasons, participants need to be able to understand fully and&#xD;
               communicate in Swedish.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Participation in another clinical trial in the past 6 months.&#xD;
  &#xD;
            -  Disease duration less than 6 months.&#xD;
  &#xD;
            -  Contraindications to physical activity: unstable coronary syndrome or myocardial&#xD;
               infarction within the preceding three months, respiratory failure (vital capacity &lt;&#xD;
               70% predicted value) or cardiac failure (ejection fraction &lt; 50% predicted value),&#xD;
               concomitant neuromuscular diseases, disabling rheumatological disease (&gt; 80%&#xD;
               disability on the Barthel scale), chronic pain or disabling orthopedic conditions,&#xD;
               hospitalization in the last three months for a serious medical or surgical condition,&#xD;
               anemia (hematocrit &lt; 30%), stroke within the previous year.&#xD;
  &#xD;
            -  MG patients already performing moderate-intensity physical activity of 150min or more&#xD;
               per week, i.e., one of the target interventions.&#xD;
  &#xD;
            -  Pregnancy.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Anna Rostedt Punga, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Uppsala University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Anna Rostedt Punga, MD, PhD</last_name>
      <phone>+46-18-4714941</phone>
      <email>anna.rostedt.punga@uu.se</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Maja Norling, BSc</last_name>
      <phone>+46-18-6110000</phone>
      <email>maja.norling@akademiska.se</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Uppsala University</name>
        <address>
          <city>Uppsala</city>
          <zip>75185</zip>
          <country>Sweden</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Anna Rostedt Punga, MD, PhD</last_name>
      </contact>
    </location>
    <location_countries>
      <country>Sweden</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>June 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 15, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>lifestyle intervention</keyword>
    <keyword>fatigue</keyword>
    <keyword>OURA</keyword>
    <keyword>physical activity</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Myasthenia Gravis</mesh_term>
      <mesh_term>Muscle Weakness</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>Not relevant.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05992025
  org study id: 2023-01455-01
  nct id: NCT05992025
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Myasthenia Gravis (MG) is a chronic autoimmune neurological disorder where an antibody attack
        of muscle receptors causes fatigable skeletal muscle weakness. In addition to fatigue,
        several MG patients experience general fatigue. Small supervised studies during 12 weeks of
        physical exercise interventions have indicated safety and beneficial neuromuscular outcomes
        in MG patients. Longer and unsupervised studies are required to obtain guidelines for
        physical activity in MG patients. Further, the development of smart rings enables remote
        digital supervision of physical activity, sleep, and biological parameters such as heart
        frequency, number of steps, and temperature. These parameters could add to the lack of
        biomarkers in MG. The project design is a randomized controlled trial with a lifestyle
        intervention to improve fatigue in the autoimmune neuromuscular disease Myasthenia Gravis
        (MG). The intervention includes digital group counseling regarding physical activity, sleep,
        general health, and digital follow-up with a "smart ring" (OURA).
  The cohort is Myasthenia Gravis (MG) patients in Sweden. The primary research question is:
        can digital lifestyle intervention in an online-group format improve fatigue as measured by
        MG-ADL in MG patients by at least 30%? Secondary research question: can lifestyle
        intervention improve fatigue as measured by FSS in MG by at least 30%?
  
        The primary outcome measure is MG-ADL; the secondary outcome measures include general fatigue
        (fatigue severity scale and Chalder´s fatigue scale). Exploratory outcome measures include
        OURA-ring-based markers, including heart rate variability, temperature fluctuations, and
        sleep and activity parameters. These will be collected throughout the entire study period for
        30 weeks.
  
        Analysis of serum biomarkers miR-150-5p and miR-30e-5p and inflammatory proteins found
        upregulated in MG will be included. Clinical data at baseline: antibody status,
        electrophysiology, MG Composite Scale (MGC), and clinical data at follow-up visits
        (medications, MGC), etc., are extracted from the medical charts and the Swedish MG registry
  
        Inclusion criteria:
  
          -  An MG diagnosis for at least six months before entry into the study.
  
          -  Both patients with ocular and generalized MG are allowed to participate.
  
          -  For practical reasons, participants need to understand Swedish.
  
        Exclusion criteria:
  
          -  Participation in another clinical trial in the past 6 months.
  
          -  Disease duration less than 6 months.
  
          -  Contraindications to physical activity: unstable coronary syndrome or myocardial
             infarction within the preceding three months, respiratory failure (vital capacity < 70%
             predicted value) or cardiac failure (ejection fraction < 50% predicted value),
             concomitant neuromuscular diseases, disabling rheumatological disease (> 80% disability
             on the Barthel scale), chronic pain or disabling orthopedic conditions, hospitalization
             in the last three months for a serious medical or surgical condition, anemia (hematocrit
             < 30%), stroke within the previous year.
  
          -  MG patients already performing a moderate-intensity physical activity of 150min or more
             per week, i.e., one of the target interventions.
  
          -  Pregnancy.
  
        Each participant is enrolled in the study for 7 months, and 26 persons are randomized to one
        of the following 3 groups:
  
          -  Group 1; no intervention, observation with the OURA ring.
  
          -  Group 2: 12 weeks of physical activity guidance with short discussions via digital
             meetings regularly. They will conduct at least 150 minutes per week of
             moderate-intensity exercises. Brisk walks are the primary choice of activity;
             alternatively, swimming, cycling, or dancing to the physical exertion according to the
             Borg scale can be performed.
  
          -  Group 3: 12 weeks of sleep exercises. The lifestyle intervention of sleep will be
             delivered via an online group, with recommended home practices between sessions. Topics
             covered will include sleep education, sleep hygiene, and practices to improve sleep
             quality.
  
        The study is digital and will use the platform "minforskning.se", which is validated
        according to GCP-GAMP5 and has the potential to collect digital consent forms.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Prospective, randomized controlled trial, parallel-group design
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  masking description: The statistician responsible for the outcome analysis will be blinded as to what intervention each group has had.
  measure: Myasthenia Gravis-Activities of Daily Living (MG-ADL)
  time frame: 7 months
  description: Subjective assessment of MG-related fatiguability. A person's score can range from zero (normal) to 24 (most severe).
  measure: Fatigue Severity Scale (FSS)
  time frame: 7 months
  description: The Fatigue Severity Scale (FSS) ranges from 0 (least fatigue) to 63 (maximum fatigue).
  measure: Chalder Fatigue Scale
  time frame: 7 months
  description: The Chalder Fatigue Scale ranges from 0 (least fatigue) to 33 (maximum fatigue)
  measure: Heart rate variability
  time frame: 7 months
  description: Heart rate variability is measured with the OURA ring.
  measure: Activity pattern
  time frame: 7 months
  description: Number of steps and minutes in moderate and high intensity activity is measured by the OURA ring.
  measure: Percentage of deep sleep
  time frame: 7 months
  description: The OURA ring measures the sleep stages, including time and percentage for deep sleep every night.
  measure: Circulating miRNA in serum
  time frame: 7 months
  description: Changes in miR-150-5p and miR-30e-5p in serum samples.
  measure: Olink Target 96 Inflammation panel of cytokines
  time frame: 7 months
  description: Changes in cytokine NPX protein values (log2 scaled) using Proximity Extension Assay (PEA) technology in serum samples
  arm group label: Observation
  arm group type: No Intervention
  description: Observation with the OURA ring and no digital meetings. The participants are offered delayed randomization after the study period. This group's outcome from the delayed randomization will be for the exploratory analysis, i.e., not in the primary analysis.
  arm group label: Physical activity
  arm group type: Experimental
  description: 12 weeks of physical activity guidance with short discussions via online group meetings according to a schedule. The participants in this arm will conduct moderate-intensity exercises for at least 150 minutes per week. Brisk walks are the primary choice of activity; alternatively, swimming, cycling, or dancing to the physical exertion according to the Borg scale can be performed.
  arm group label: Sleep hygiene intervention
  arm group type: Active Comparator
  description: 12 weeks of sleep exercises. The lifestyle intervention of sleep will be delivered via an online group, with recommended home practices between sessions. Topics covered will include sleep education, sleep hygiene, and practices to improve sleep quality.
  intervention type: Behavioral
  intervention name: Physical activity
  description: Intervention with physical activity more than 150 minutes of medium to high intensity per week.
  arm group label: Physical activity
  intervention type: Behavioral
  intervention name: Sleep hygiene
  description: Intervention with sleep hygiene to optimize sleep duration and quality.
  arm group label: Sleep hygiene intervention
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 90 Years
  healthy volunteers: No
  last name: Anna Rostedt Punga, MD, PhD
  role: Principal Investigator
  affiliation: Uppsala University
  last name: Anna Rostedt Punga, MD, PhD
  phone: +46-18-4714941
  email: anna.rostedt.punga@uu.se
  last name: Maja Norling, BSc
  phone: +46-18-6110000
  email: maja.norling@akademiska.se
  facility: 
  status: Recruiting
  contact: 
  country: Sweden
  responsible party type: Sponsor
  mesh term: Myasthenia Gravis
  mesh term: Muscle Weakness
  sharing ipd: No
  ipd description: Not relevant.