<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/NCT01675271</url>
  </required_header>
  <id_info>
    <org_study_id>300/E9/06</org_study_id>
    <nct_id>NCT01675271</nct_id>
  </id_info>
  <brief_title>Autonomic Nervous System and Exercise In Gestational Diabetes</brief_title>
  <acronym>ANS-EXE</acronym>
  <official_title>Effect Of Individual Exercise Prescription On Cardiovascular Risk Factors In Woman At Risk For Gestational Diabetes - Focus On Autonomic Nervous System And Inflammation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Helsinki University Central Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Helsinki University Central Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The focus of this study is on individualized exercise prescription on primary prevention of&#xD;
      cardiovascular diseases (CVD). Special attention is set on autonomic nervous system function&#xD;
      and inflammation.&#xD;
&#xD;
      This study will seek novel, cost-effective models of exercise prescription that will&#xD;
      emphasize individuals own response on her health and which would be easily implemented to&#xD;
      primary health care as primary prevention for CVD. According to power calculation,sixty women&#xD;
      planning pregnancy with BMI equal or over 30 and/or history of GDM will be recruited and&#xD;
      randomized to an individual exercise arm (n=20), a general exercise arm (n=20) and a control&#xD;
      arm (n=20). General intervention group will receive general exercise and dietary counselling&#xD;
      whereas a personal exercise and dietary programs will be planned for individualized exercise&#xD;
      group. Those randomized to the control arm will receive no dietary and exercise information.&#xD;
&#xD;
      Clinical exercise tests and autonomic nervous system tests will be performed in the beginning&#xD;
      of the study and after 3 months intervention. Blood samples for markers of inflammation,&#xD;
      glucose homeostasis and lipid status will be collected from prepregnancy period until 1 years&#xD;
      after delivery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Gestational diabetes (GDM) is one of the earliest signs for increased risk of developing CVD.&#xD;
      In addition to this independent association, GDM increases CVD risk through type 2 diabetes.&#xD;
      The physiological basis for his disease progression is not yet fully understood. Increasing&#xD;
      evidence exists on interplay of insulin resistance and subclinical inflammation, and more&#xD;
      recently on unbalance of the autonomic nervous system.&#xD;
&#xD;
      There is unequivocal evidence that increased physical activity and regular exercise can&#xD;
      prevent risk factors that give rise to cardiovascular complications. According to a recent&#xD;
      meta-analysis, exercise started before and continued throughout pregnancy may lead to marked&#xD;
      GDM risk reduction. Unfortunately, exercise in most lifestyle studies is usually unstructured&#xD;
      or unsupervised or does not meet current guidelines. There is also a significant gap in our&#xD;
      understanding of how to target, deliver and prescribe the beneficial type of exercise to&#xD;
      patients at risk in the community.&#xD;
&#xD;
      Sixty women planning pregnancy with BMI equal or over 30 and/or history of GDM will be&#xD;
      recruited and randomized to an individual exercise arm (n=20), a general exercise arm (n=20)&#xD;
      and a control arm (n=20). General intervention group will receive general exercise and&#xD;
      dietary counselling whereas a personal exercise and dietary programs will be planned for&#xD;
      individualized exercise group. Those randomized to the control arm will receive no dietary&#xD;
      and exercise information. All subjects will be followed by diabetes nurses every 3 months as&#xD;
      follows: at the time of recruitment, after 3 months intervention period, int the 1st, 2nd and&#xD;
      3rd trimester of pregnancy and 6 weeks, 6 months and 1 year postpartum. The following&#xD;
      measurements will be performed at every visit:blood pressure, weight, waist-to-hip ratio,&#xD;
      glucose homeostasis (2-h OGTT, Pf- insulin, Pf- glucose, insulin resistance (Homa-IR),&#xD;
      GHbA1c, lipids (total cholesterol, LDL, HDL, triglycerides), inflammatory markers&#xD;
      (sCRP,S-amyloid A, IL-1 and 6, alpha 1-glycoprotein, SHBG), adipokines (endothelin,&#xD;
      adrenomedullin, adiponectin),dipeptidyl peptidase-4 (DPP-4), atrial natriuretic peptides&#xD;
      (ANP, proBNP).For all study participants, 15 D and EDPS questionnaires are used for&#xD;
      assessment of quality of life and mental health. Registered costs of the intervention will be&#xD;
      calculated for cost-effectiveness analysis.&#xD;
&#xD;
      Both endurance and strength training will be included in the exercise program of the&#xD;
      individual exercise study group. Heart rate will be monitored with heart rate belt and&#xD;
      registered in internet-based exercise diary which can be instantly followed by the exercise&#xD;
      professionals. This information will be used for fine-tuning of their exercise prescription&#xD;
      during the intervention period. Diet and weight target will be planned individually by a&#xD;
      dietician. Actualized diet will be registered in an internet-based diary instantly followed&#xD;
      by the study dietician who will guide the subjects personally by e-mail and suggest further&#xD;
      dietary changes if needed.&#xD;
&#xD;
      All subjects will perform an exercise test in the beginning of the study and after 3 months&#xD;
      intervention with a step incremental protocol on a cycle ergometer until volitional fatigue.&#xD;
      Extensive and advanced technologies will be used to monitor exercise responses, including&#xD;
      breath-by-breath ventilation and alveolar gas exchange; exercise ECG; impedance cardiography;&#xD;
      automatic arterial blood pressure; analysis system for heart rate variability and blood&#xD;
      pressure variability, baroreflex sensitivity, muscle electrical activity, arterial O2&#xD;
      saturation and local cerebral and muscle tissue oxygenation with near-infrared spectroscopy.&#xD;
      The autonomic nervous system measurements, including 24 hour ECG monitoring, heart rate&#xD;
      variability assessment with controlled breathing rate, the orthostatic test and a 5 min&#xD;
      handgrip test, will be performed during another visit to the laboratory. Total haemoglobin&#xD;
      mass and blood volume will be determined by carbonmonoxy rebreathing method.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2012</start_date>
  <completion_date type="Actual">January 2016</completion_date>
  <primary_completion_date type="Actual">September 2015</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>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>VO2max</measure>
    <time_frame>after 3 months training</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart rate variability</measure>
    <time_frame>6 weeks postpartum</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>autonomic nervous system function</measure>
    <time_frame>after 3 months training</time_frame>
    <description>heart rate variability, baroreflex sensitivity, handgrip test</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life</measure>
    <time_frame>1 year after delivery</time_frame>
    <description>15D questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>mental health</measure>
    <time_frame>1 year after delivery</time_frame>
    <description>EDPS questionnaire</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Gestational Diabetes</condition>
  <condition>Cardiovascular Risk Factors</condition>
  <arm_group>
    <arm_group_label>individual exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>individualized exercise program</description>
  </arm_group>
  <arm_group>
    <arm_group_label>general exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>general exercise program</description>
  </arm_group>
  <arm_group>
    <arm_group_label>control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No exercise and dietary counselling</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>individual exercise</intervention_name>
    <description>individual exercise and dietary prescription</description>
    <arm_group_label>individual exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>general exercise</intervention_name>
    <description>general exercise counselling</description>
    <arm_group_label>general exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  trying to become pregnant&#xD;
&#xD;
          -  BMI equal or over 30 and/or history of gestational diabetes&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  diagnosed diabetes&#xD;
&#xD;
          -  smoking&#xD;
&#xD;
          -  user of peroral glucocorticoids&#xD;
&#xD;
          -  user of SSRI medication&#xD;
&#xD;
          -  physical or psychological disability&#xD;
&#xD;
          -  significant co-operation difficulties (e.g. insufficient language skills)&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aila Tiitinen, professor</last_name>
    <role>Study Director</role>
    <affiliation>Helsinki University Central Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Helsinki University Central Hospital / dept of Obstetrics and Gynecology</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <reference>
    <citation>Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009 May 23;373(9677):1773-9. doi: 10.1016/S0140-6736(09)60731-5.</citation>
    <PMID>19465232</PMID>
  </reference>
  <reference>
    <citation>Carr DB, Utzschneider KM, Hull RL, Tong J, Wallace TM, Kodama K, Shofer JB, Heckbert SR, Boyko EJ, Fujimoto WY, Kahn SE. Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes. Diabetes Care. 2006 Sep;29(9):2078-83. doi: 10.2337/dc05-2482.</citation>
    <PMID>16936156</PMID>
  </reference>
  <reference>
    <citation>Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc. 2007 Aug;39(8):1423-34. doi: 10.1249/mss.0b013e3180616b27.</citation>
    <PMID>17762377</PMID>
  </reference>
  <reference>
    <citation>Tobias DK, Zhang C, van Dam RM, Bowers K, Hu FB. Physical activity before and during pregnancy and risk of gestational diabetes mellitus: a meta-analysis. Diabetes Care. 2011 Jan;34(1):223-9. doi: 10.2337/dc10-1368. Epub 2010 Sep 27.</citation>
    <PMID>20876206</PMID>
  </reference>
  <reference>
    <citation>Poyhonen-Alho M, Viitasalo M, Nicholls MG, Lindstrom BM, Vaananen H, Kaaja R. Imbalance of the autonomic nervous system at night in women with gestational diabetes. Diabet Med. 2010 Sep;27(9):988-94. doi: 10.1111/j.1464-5491.2010.03062.x.</citation>
    <PMID>20722671</PMID>
  </reference>
  <reference>
    <citation>Poyhonen-Alho M, Ebeling P, Saarinen A, Kaaja R. Decreased variation of inflammatory markers in gestational diabetes. Diabetes Metab Res Rev. 2011 Mar;27(3):269-76. doi: 10.1002/dmrr.1170.</citation>
    <PMID>21309051</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>June 17, 2012</study_first_submitted>
  <study_first_submitted_qc>August 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 29, 2012</study_first_posted>
  <last_update_submitted>November 1, 2018</last_update_submitted>
  <last_update_submitted_qc>November 1, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Helsinki University Central Hospital</investigator_affiliation>
    <investigator_full_name>Maritta Poyhonen-Alho</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>gestational diabetes</keyword>
  <keyword>inflammation</keyword>
  <keyword>autonomic nervous system</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes, Gestational</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
  </condition_browse>
  <!-- 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/NCT01675271
org study id: 300/E9/06
nct id: NCT01675271
lead sponsor: 
has dmc: No
The focus of this study is on individualized exercise prescription on primary prevention of
      cardiovascular diseases (CVD). Special attention is set on autonomic nervous system function
      and inflammation.

      This study will seek novel, cost-effective models of exercise prescription that will
      emphasize individuals own response on her health and which would be easily implemented to
      primary health care as primary prevention for CVD. According to power calculation,sixty women
      planning pregnancy with BMI equal or over 30 and/or history of GDM will be recruited and
      randomized to an individual exercise arm (n=20), a general exercise arm (n=20) and a control
      arm (n=20). General intervention group will receive general exercise and dietary counselling
      whereas a personal exercise and dietary programs will be planned for individualized exercise
      group. Those randomized to the control arm will receive no dietary and exercise information.

      Clinical exercise tests and autonomic nervous system tests will be performed in the beginning
      of the study and after 3 months intervention. Blood samples for markers of inflammation,
      glucose homeostasis and lipid status will be collected from prepregnancy period until 1 years
      after delivery.
Gestational diabetes (GDM) is one of the earliest signs for increased risk of developing CVD.
      In addition to this independent association, GDM increases CVD risk through type 2 diabetes.
      The physiological basis for his disease progression is not yet fully understood. Increasing
      evidence exists on interplay of insulin resistance and subclinical inflammation, and more
      recently on unbalance of the autonomic nervous system.

      There is unequivocal evidence that increased physical activity and regular exercise can
      prevent risk factors that give rise to cardiovascular complications. According to a recent
      meta-analysis, exercise started before and continued throughout pregnancy may lead to marked
      GDM risk reduction. Unfortunately, exercise in most lifestyle studies is usually unstructured
      or unsupervised or does not meet current guidelines. There is also a significant gap in our
      understanding of how to target, deliver and prescribe the beneficial type of exercise to
      patients at risk in the community.

      Sixty women planning pregnancy with BMI equal or over 30 and/or history of GDM will be
      recruited and randomized to an individual exercise arm (n=20), a general exercise arm (n=20)
      and a control arm (n=20). General intervention group will receive general exercise and
      dietary counselling whereas a personal exercise and dietary programs will be planned for
      individualized exercise group. Those randomized to the control arm will receive no dietary
      and exercise information. All subjects will be followed by diabetes nurses every 3 months as
      follows: at the time of recruitment, after 3 months intervention period, int the 1st, 2nd and
      3rd trimester of pregnancy and 6 weeks, 6 months and 1 year postpartum. The following
      measurements will be performed at every visit:blood pressure, weight, waist-to-hip ratio,
      glucose homeostasis (2-h OGTT, Pf- insulin, Pf- glucose, insulin resistance (Homa-IR),
      GHbA1c, lipids (total cholesterol, LDL, HDL, triglycerides), inflammatory markers
      (sCRP,S-amyloid A, IL-1 and 6, alpha 1-glycoprotein, SHBG), adipokines (endothelin,
      adrenomedullin, adiponectin),dipeptidyl peptidase-4 (DPP-4), atrial natriuretic peptides
      (ANP, proBNP).For all study participants, 15 D and EDPS questionnaires are used for
      assessment of quality of life and mental health. Registered costs of the intervention will be
      calculated for cost-effectiveness analysis.

      Both endurance and strength training will be included in the exercise program of the
      individual exercise study group. Heart rate will be monitored with heart rate belt and
      registered in internet-based exercise diary which can be instantly followed by the exercise
      professionals. This information will be used for fine-tuning of their exercise prescription
      during the intervention period. Diet and weight target will be planned individually by a
      dietician. Actualized diet will be registered in an internet-based diary instantly followed
      by the study dietician who will guide the subjects personally by e-mail and suggest further
      dietary changes if needed.

      All subjects will perform an exercise test in the beginning of the study and after 3 months
      intervention with a step incremental protocol on a cycle ergometer until volitional fatigue.
      Extensive and advanced technologies will be used to monitor exercise responses, including
      breath-by-breath ventilation and alveolar gas exchange; exercise ECG; impedance cardiography;
      automatic arterial blood pressure; analysis system for heart rate variability and blood
      pressure variability, baroreflex sensitivity, muscle electrical activity, arterial O2
      saturation and local cerebral and muscle tissue oxygenation with near-infrared spectroscopy.
      The autonomic nervous system measurements, including 24 hour ECG monitoring, heart rate
      variability assessment with controlled breathing rate, the orthostatic test and a 5 min
      handgrip test, will be performed during another visit to the laboratory. Total haemoglobin
      mass and blood volume will be determined by carbonmonoxy rebreathing method.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: VO2max
time frame: after 3 months training
measure: Heart rate variability
time frame: 6 weeks postpartum
measure: autonomic nervous system function
time frame: after 3 months training
description: heart rate variability, baroreflex sensitivity, handgrip test
measure: quality of life
time frame: 1 year after delivery
description: 15D questionnaire
measure: mental health
time frame: 1 year after delivery
description: EDPS questionnaire
arm group label: individual exercise
arm group type: Active Comparator
description: individualized exercise program
arm group label: general exercise
arm group type: Active Comparator
description: general exercise program
arm group label: control
arm group type: No Intervention
description: No exercise and dietary counselling
intervention type: Other
intervention name: individual exercise
description: individual exercise and dietary prescription
arm group label: individual exercise
intervention type: Other
intervention name: general exercise
description: general exercise counselling
arm group label: general exercise
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Aila Tiitinen, professor
role: Study Director
affiliation: Helsinki University Central Hospital
facility: 
country: Finland
citation: Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009 May 23;373(9677):1773-9. doi: 10.1016/S0140-6736(09)60731-5.
PMID: 19465232
citation: Carr DB, Utzschneider KM, Hull RL, Tong J, Wallace TM, Kodama K, Shofer JB, Heckbert SR, Boyko EJ, Fujimoto WY, Kahn SE. Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes. Diabetes Care. 2006 Sep;29(9):2078-83. doi: 10.2337/dc05-2482.
PMID: 16936156
citation: Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, Macera CA, Heath GW, Thompson PD, Bauman A. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Med Sci Sports Exerc. 2007 Aug;39(8):1423-34. doi: 10.1249/mss.0b013e3180616b27.
PMID: 17762377
citation: Tobias DK, Zhang C, van Dam RM, Bowers K, Hu FB. Physical activity before and during pregnancy and risk of gestational diabetes mellitus: a meta-analysis. Diabetes Care. 2011 Jan;34(1):223-9. doi: 10.2337/dc10-1368. Epub 2010 Sep 27.
PMID: 20876206
citation: Poyhonen-Alho M, Viitasalo M, Nicholls MG, Lindstrom BM, Vaananen H, Kaaja R. Imbalance of the autonomic nervous system at night in women with gestational diabetes. Diabet Med. 2010 Sep;27(9):988-94. doi: 10.1111/j.1464-5491.2010.03062.x.
PMID: 20722671
citation: Poyhonen-Alho M, Ebeling P, Saarinen A, Kaaja R. Decreased variation of inflammatory markers in gestational diabetes. Diabetes Metab Res Rev. 2011 Mar;27(3):269-76. doi: 10.1002/dmrr.1170.
PMID: 21309051
responsible party type: Principal Investigator
investigator affiliation: Helsinki University Central Hospital
investigator full name: Maritta Poyhonen-Alho
investigator title: MD, PhD
mesh term: Diabetes, Gestational
mesh term: Diabetes Mellitus