<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/NCT03300635</url>
  </required_header>
  <id_info>
    <org_study_id>TYH2017215</org_study_id>
    <nct_id>NCT03300635</nct_id>
  </id_info>
  <brief_title>Metabolism, Muscle Function and Psychological Factors in Fibromyalgia</brief_title>
  <official_title>Metaboliset Muutokset ja Lihastoiminta Fibromyalgiassa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helsinki University Central Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Helsinki</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Helsinki University Central Hospital</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>
      Fibromyalgia (FM) is a world widely common syndrome, characterized by widespread pain, often&#xD;
      accompanied by general fatigue, soreness, and abnormal sensations (like &quot;pins and needles&quot;).&#xD;
      The reasons and the mechanisms (pathogenesis) of FM are still poorly understood. Efficacious&#xD;
      therapies cannot be developed without understanding the pathophysiological mechanisms of the&#xD;
      disease or syndrome.&#xD;
&#xD;
      FM patients suffer from pain and sense of weakness and fatigue in the muscles, and often&#xD;
      report difficulty in relaxing their muscles. So far, the studies on muscle activation in&#xD;
      fibromyalgia (mostly using surface electromyography) have shown some unusual functioning, a&#xD;
      kind of overuse, but the results have been somewhat contradictory.&#xD;
&#xD;
      FM symptoms share some features with small fibre neuropathy, which is a disease or&#xD;
      abnormality of small nerve fibres with a diverse aetiology. Recently, several research groups&#xD;
      have shown (studying both the electrical function of superficial nerves and nerve endings of&#xD;
      skin samples) that up to 50% of the FM patients with severe symptoms have small fibre&#xD;
      neuropathy: their small nerves do not function properly and small nerve fibre density in&#xD;
      their skin is reduced. However, as this phenomenon is common but not a rule, it might be&#xD;
      rather a consequence of some underlying mechanisms of the syndrome, creating even more&#xD;
      symptoms.&#xD;
&#xD;
      The aim is to investigate whether there would exist metabolic changes in FM patients that&#xD;
      would create pain and lead to functional changes and damage in small nerve fibres. The&#xD;
      investigators also aim to explore the muscle function particularly in distressed situations&#xD;
      and at rest. The hypothesis is that a towards-overuse-altered function would create&#xD;
      unfavourable metabolic changes. Third, the aim is to investigate some psychological factors&#xD;
      (such as tendency to get anxious or distressed) to find out, if there is any association&#xD;
      between them and muscle function.&#xD;
&#xD;
      The FM patients as well as healthy control subjects will be recruited at Helsinki University&#xD;
      Hospital Pain Clinic and from primary care at Vantaa Health Care Centre. The voluntary test&#xD;
      subjects will attend&#xD;
&#xD;
        1. A muscle function examination of 30 minutes with electromyography using surface&#xD;
           electrodes, including mentally distressing tasks and relaxing periods. At the same&#xD;
           session, the subject will reply to some questionnaires regarding their symptoms and&#xD;
           measuring some psychological factors. Actual pain level will be assessed.&#xD;
&#xD;
        2. A glucose tolerance test, with other blood samples&#xD;
&#xD;
        3. A bicycle ergometer exercise test of 20 - 30 minutes, with both physiological and&#xD;
           chemical (blood samples) recordings. Actual pain level will be assessed as well.&#xD;
&#xD;
      At this stage, 40 patients and 20 healthy control subjects will be recruited.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 5, 2015</start_date>
  <completion_date type="Actual">April 10, 2019</completion_date>
  <primary_completion_date type="Actual">April 10, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Patients and healthy control subjects will attend the same interventions: a) muscle function test (distressing task vs. relaxing) with e.g. psychological questionnaires, b) glucose tolerance test and other blood analyses including metabolomics, and c) bicycle ergometry with physiological measurements and blood analyses including metabolomics.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>metabolomics</measure>
    <time_frame>up to day 3</time_frame>
    <description>the difference of value distribution in metabolics panel between groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>metabolomics (physical stress)</measure>
    <time_frame>Day 3 (at the end of Exercise test)</time_frame>
    <description>the difference of value distribution in metabolics panel between groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>metabolomics (metabolic stress)</measure>
    <time_frame>Day 2 ( at the end of Glucose test)</time_frame>
    <description>the difference of value distribution in metabolics panel between groups</description>
  </primary_outcome>
  <primary_outcome>
    <measure>muscle function (raw)</measure>
    <time_frame>Day 1</time_frame>
    <description>sEMG signal amplitude</description>
  </primary_outcome>
  <primary_outcome>
    <measure>muscle function (normalized)</measure>
    <time_frame>Day 1</time_frame>
    <description>normalized signal amplitude (%sEMGmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>muscle rest time</measure>
    <time_frame>Day 1</time_frame>
    <description>time of sEMG signal amplitude &lt; 0.5% sEMGmax</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Perceived distress during mental stress vs. relaxation (baseline)</measure>
    <time_frame>Day 1 ( at the beginning of the recording during the Mental distress and relaxation test)</time_frame>
    <description>reported distress intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived distress during mental stress vs. relaxation (relaxation I)</measure>
    <time_frame>Day 1 (after the first relaxation phase of the Mental distress and relaxation test)</time_frame>
    <description>reported distress intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived distress during mental stress vs. relaxation (mental stress I)</measure>
    <time_frame>Day 1 (after the first mental stress phase of the Mental distress and relaxation test)</time_frame>
    <description>reported distress intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived distress during mental stress vs. relaxation (relaxation II)</measure>
    <time_frame>Day 1 (after the second relaxation phase of the Mental distress and relaxation test)</time_frame>
    <description>reported distress intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived distress during mental stress vs. relaxation (mental stress II)</measure>
    <time_frame>Day 1 (after the second mental stress phase of the Mental distress and relaxation test)</time_frame>
    <description>reported distress intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Perceived distress during mental stress vs. relaxation (relaxation III)</measure>
    <time_frame>Day 1 ( after the third relaxation phase of the Mental distress and relaxation test)</time_frame>
    <description>reported distress intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity during mental stress vs. relaxation (baseline)</measure>
    <time_frame>Day 1 ( at the beginning of the recording during the Mental distress and relaxation test)</time_frame>
    <description>reported pain intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity during mental stress vs. relaxation (relaxation I)</measure>
    <time_frame>Day 1 ( after the first relaxation phase of the Mental distress and relaxation test)</time_frame>
    <description>reported pain intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity during mental stress vs. relaxation (mental stress I)</measure>
    <time_frame>Day 1 ( after the first mental stress phase of the Mental distress and relaxation test)</time_frame>
    <description>reported pain intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity during mental stress vs. relaxation (relaxation II)</measure>
    <time_frame>Day 1 (after the second relaxation phase of the Mental distress and relaxation test)</time_frame>
    <description>reported pain intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity during mental stress vs. relaxation (mental stress II)</measure>
    <time_frame>Day 1 (after the second mental stress phase of the Mental distress and relaxation test)</time_frame>
    <description>reported pain intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain intensity during mental stress vs. relaxation (relaxation III)</measure>
    <time_frame>Day 1 (after the third relaxation phase of the Mental distress and relaxation test)</time_frame>
    <description>reported pain intensity (NRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>heart rate variability</measure>
    <time_frame>Day 1</time_frame>
    <description>variability of heart beat interval evaluated as root mean square successive difference (RMSSD)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">81</enrollment>
  <condition>Fibromyalgia</condition>
  <arm_group>
    <arm_group_label>Fibromyalgia patients</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy controls</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Mental distress and relaxation test</intervention_name>
    <arm_group_label>Fibromyalgia patients</arm_group_label>
    <arm_group_label>Healthy controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Glucose tolerance test</intervention_name>
    <arm_group_label>Fibromyalgia patients</arm_group_label>
    <arm_group_label>Healthy controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exercise test</intervention_name>
    <arm_group_label>Fibromyalgia patients</arm_group_label>
    <arm_group_label>Healthy controls</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  fibromyalgia diagnosed by the researchers RM or TZ, based on the ACR criteria from&#xD;
             1990&#xD;
&#xD;
          -  Finnish as native language&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  male sex&#xD;
&#xD;
          -  muscular or neuromuscular diseases&#xD;
&#xD;
          -  diabetes&#xD;
&#xD;
          -  heart disease&#xD;
&#xD;
          -  generalised atherosclerosis&#xD;
&#xD;
          -  untreated hypertension&#xD;
&#xD;
          -  neurological or other disease that systematically affects muscles&#xD;
&#xD;
          -  a severe psychiatric disorder&#xD;
&#xD;
          -  regular consumption of beta-blockers, bronchodilators, or statins&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>The Finnish personal ID system includes identification of gender. As most of clinical FM patients are women, we exclude men to create as much homogenity as possible in our sample.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eija A Kalso, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Helsinki University Hospital and Helsinki University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>HelsinkiUCH</name>
      <address>
        <city>Helsinki</city>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>September 12, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>December 12, 2019</last_update_submitted>
  <last_update_submitted_qc>December 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Helsinki University Central Hospital</investigator_affiliation>
    <investigator_full_name>Ritva Markkula</investigator_full_name>
    <investigator_title>Principal Investigator, specialist doctor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fibromyalgia</mesh_term>
    <mesh_term>Myofascial Pain Syndromes</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data are available for only two of the researchers, Ritva Markkula and Teemu Zetterman, who are recruiting the subjects and collecting and coding their personal data to an unidentified mode.</ipd_description>
  </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/NCT03300635
org study id: TYH2017215
nct id: NCT03300635
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Fibromyalgia (FM) is a world widely common syndrome, characterized by widespread pain, often
      accompanied by general fatigue, soreness, and abnormal sensations (like "pins and needles").
      The reasons and the mechanisms (pathogenesis) of FM are still poorly understood. Efficacious
      therapies cannot be developed without understanding the pathophysiological mechanisms of the
      disease or syndrome.

      FM patients suffer from pain and sense of weakness and fatigue in the muscles, and often
      report difficulty in relaxing their muscles. So far, the studies on muscle activation in
      fibromyalgia (mostly using surface electromyography) have shown some unusual functioning, a
      kind of overuse, but the results have been somewhat contradictory.

      FM symptoms share some features with small fibre neuropathy, which is a disease or
      abnormality of small nerve fibres with a diverse aetiology. Recently, several research groups
      have shown (studying both the electrical function of superficial nerves and nerve endings of
      skin samples) that up to 50% of the FM patients with severe symptoms have small fibre
      neuropathy: their small nerves do not function properly and small nerve fibre density in
      their skin is reduced. However, as this phenomenon is common but not a rule, it might be
      rather a consequence of some underlying mechanisms of the syndrome, creating even more
      symptoms.

      The aim is to investigate whether there would exist metabolic changes in FM patients that
      would create pain and lead to functional changes and damage in small nerve fibres. The
      investigators also aim to explore the muscle function particularly in distressed situations
      and at rest. The hypothesis is that a towards-overuse-altered function would create
      unfavourable metabolic changes. Third, the aim is to investigate some psychological factors
      (such as tendency to get anxious or distressed) to find out, if there is any association
      between them and muscle function.

      The FM patients as well as healthy control subjects will be recruited at Helsinki University
      Hospital Pain Clinic and from primary care at Vantaa Health Care Centre. The voluntary test
      subjects will attend

        1. A muscle function examination of 30 minutes with electromyography using surface
           electrodes, including mentally distressing tasks and relaxing periods. At the same
           session, the subject will reply to some questionnaires regarding their symptoms and
           measuring some psychological factors. Actual pain level will be assessed.

        2. A glucose tolerance test, with other blood samples

        3. A bicycle ergometer exercise test of 20 - 30 minutes, with both physiological and
           chemical (blood samples) recordings. Actual pain level will be assessed as well.

      At this stage, 40 patients and 20 healthy control subjects will be recruited.
allocation: Non-Randomized
intervention model: Parallel Assignment
intervention model description: Patients and healthy control subjects will attend the same interventions: a) muscle function test (distressing task vs. relaxing) with e.g. psychological questionnaires, b) glucose tolerance test and other blood analyses including metabolomics, and c) bicycle ergometry with physiological measurements and blood analyses including metabolomics.
primary purpose: Other
masking: Single (Outcomes Assessor)
measure: metabolomics
time frame: up to day 3
description: the difference of value distribution in metabolics panel between groups
measure: metabolomics (physical stress)
time frame: Day 3 (at the end of Exercise test)
description: the difference of value distribution in metabolics panel between groups
measure: metabolomics (metabolic stress)
time frame: Day 2 ( at the end of Glucose test)
description: the difference of value distribution in metabolics panel between groups
measure: muscle function (raw)
time frame: Day 1
description: sEMG signal amplitude
measure: muscle function (normalized)
time frame: Day 1
description: normalized signal amplitude (%sEMGmax)
measure: muscle rest time
time frame: Day 1
description: time of sEMG signal amplitude < 0.5% sEMGmax
measure: Perceived distress during mental stress vs. relaxation (baseline)
time frame: Day 1 ( at the beginning of the recording during the Mental distress and relaxation test)
description: reported distress intensity (NRS)
measure: Perceived distress during mental stress vs. relaxation (relaxation I)
time frame: Day 1 (after the first relaxation phase of the Mental distress and relaxation test)
description: reported distress intensity (NRS)
measure: Perceived distress during mental stress vs. relaxation (mental stress I)
time frame: Day 1 (after the first mental stress phase of the Mental distress and relaxation test)
description: reported distress intensity (NRS)
measure: Perceived distress during mental stress vs. relaxation (relaxation II)
time frame: Day 1 (after the second relaxation phase of the Mental distress and relaxation test)
description: reported distress intensity (NRS)
measure: Perceived distress during mental stress vs. relaxation (mental stress II)
time frame: Day 1 (after the second mental stress phase of the Mental distress and relaxation test)
description: reported distress intensity (NRS)
measure: Perceived distress during mental stress vs. relaxation (relaxation III)
time frame: Day 1 ( after the third relaxation phase of the Mental distress and relaxation test)
description: reported distress intensity (NRS)
measure: Pain intensity during mental stress vs. relaxation (baseline)
time frame: Day 1 ( at the beginning of the recording during the Mental distress and relaxation test)
description: reported pain intensity (NRS)
measure: Pain intensity during mental stress vs. relaxation (relaxation I)
time frame: Day 1 ( after the first relaxation phase of the Mental distress and relaxation test)
description: reported pain intensity (NRS)
measure: Pain intensity during mental stress vs. relaxation (mental stress I)
time frame: Day 1 ( after the first mental stress phase of the Mental distress and relaxation test)
description: reported pain intensity (NRS)
measure: Pain intensity during mental stress vs. relaxation (relaxation II)
time frame: Day 1 (after the second relaxation phase of the Mental distress and relaxation test)
description: reported pain intensity (NRS)
measure: Pain intensity during mental stress vs. relaxation (mental stress II)
time frame: Day 1 (after the second mental stress phase of the Mental distress and relaxation test)
description: reported pain intensity (NRS)
measure: Pain intensity during mental stress vs. relaxation (relaxation III)
time frame: Day 1 (after the third relaxation phase of the Mental distress and relaxation test)
description: reported pain intensity (NRS)
measure: heart rate variability
time frame: Day 1
description: variability of heart beat interval evaluated as root mean square successive difference (RMSSD)
arm group label: Fibromyalgia patients
arm group type: Other
description: All study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test
arm group label: Healthy controls
arm group type: Other
description: All study subjects, both patients and healthy controls, will attend all three interventions: Mental distress and relaxation test, Glucose tolerance test, and Exercise test
intervention type: Other
intervention name: Mental distress and relaxation test
arm group label: Fibromyalgia patients
arm group label: Healthy controls
intervention type: Other
intervention name: Glucose tolerance test
arm group label: Fibromyalgia patients
arm group label: Healthy controls
intervention type: Other
intervention name: Exercise test
arm group label: Fibromyalgia patients
arm group label: Healthy controls
criteria: 
gender: Female
gender based: Yes
gender description: The Finnish personal ID system includes identification of gender. As most of clinical FM patients are women, we exclude men to create as much homogenity as possible in our sample.
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Eija A Kalso, MD, PhD
role: Study Chair
affiliation: Helsinki University Hospital and Helsinki University
facility: 
country: Finland
responsible party type: Principal Investigator
investigator affiliation: Helsinki University Central Hospital
investigator full name: Ritva Markkula
investigator title: Principal Investigator, specialist doctor
mesh term: Fibromyalgia
mesh term: Myofascial Pain Syndromes
sharing ipd: Yes
ipd description: Individual participant data are available for only two of the researchers, Ritva Markkula and Teemu Zetterman, who are recruiting the subjects and collecting and coding their personal data to an unidentified mode.