<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/NCT02224976</url>
  </required_header>
  <id_info>
    <org_study_id>FL94</org_study_id>
    <nct_id>NCT02224976</nct_id>
  </id_info>
  <brief_title>Effect of Intense Training on Ovarian Function and Bone Turnover</brief_title>
  <official_title>Impact of Intense Exercise Training on Energy Availability, Ovarian Function and Bone Turnover in Female Athletes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>USDA, Western Human Nutrition Research Center</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of California, Davis</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>USDA, Western Human Nutrition Research Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators propose a prospective, longitudinal, department funded study protocol to&#xD;
      evaluate whether changes in energy availability, during a period of highly intensified&#xD;
      exercise training, will increase bone turnover markers and decrease ovarian function and&#xD;
      exercise performance, in a dose-dependent fashion in competitive female athletes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Female athletes participating in sports which emphasize leanness as a factor to success,&#xD;
      while also imposing large exercise training loads, present a high prevalence of endocrine and&#xD;
      metabolic alterations linked to low energy stores, including suppressed ovarian function and&#xD;
      bone loss. Increased bone turnover resulting from low energy stores and suppressed estrogen&#xD;
      production may hold the most adverse consequences for long term health, increasing the risk&#xD;
      of premature osteopenia, while increasing the risk of stress fractures in the short term.&#xD;
      Chronically low energy stores may also contribute to the development of overreaching and&#xD;
      overtraining syndromes, characterized by excessive, lasting fatigue and long-term decreases&#xD;
      in performance, which can compromise these athletes' health and athletic career. The&#xD;
      investigators propose the first longitudinal study aiming to demonstrate the link between low&#xD;
      energy status, impaired ovarian function, bone turnover and decreased performance in&#xD;
      free-living, competitive female athletes. After a 4-week baseline period of habitual&#xD;
      training, athletes will undergo 4 weeks of intensified training (IT), during which the&#xD;
      exercise load is increased by 30% from their individual baseline load in order to sharply&#xD;
      increase energy expenditure. As athletes will be let to freely adjust their food intake, the&#xD;
      investigators aim to test the hypothesis that athletes will fail to adjust food intake&#xD;
      sufficiently to match energy expenditure, and that the resulting decrease in energy&#xD;
      availability (EA, energy intake - energy expenditure from exercise) will influence, in a&#xD;
      dose-dependent fashion, the suppression of estrogen production, the increase in bone turnover&#xD;
      and the severity of performance decrement. The IT period will then be followed by a 2-week&#xD;
      taper (REC), in which exercise training volume will be reduced by 50% from baseline. The&#xD;
      investigators will assess whether EA returns to baseline values, and characterize changes in&#xD;
      bone turnover during this recovery period. It is hypothesized that any improvements in&#xD;
      exercise performance resulting from IT + REC will occur in athletes who were able to remain&#xD;
      closest to a balanced energy state during IT. Concretely linking EA to both performance and&#xD;
      bone health may incentivize female athletes to adopt more adequate feeding behaviors for&#xD;
      their activity level.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2014</start_date>
  <completion_date type="Actual">December 2015</completion_date>
  <primary_completion_date type="Actual">December 2015</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in energy availability (energy intake - energy expenditure of physical activity)</measure>
    <time_frame>Baseline (week 4), after 4 weeks of intensified training (week 8) and after a two-week recovery period (week 10)</time_frame>
    <description>The investigators aim to capture the spectrum and variability of energy availability in endurance athletes under normal training conditions, describing in detail training regimen, total energy expenditure and nutrition habits during three distinct phases of training that are habitually followed by endurance athletes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in athletic performance</measure>
    <time_frame>Baseline (week 4), after 4 weeks of intensified training (week 8) and after a two-week recovery period (week 10)</time_frame>
    <description>The investigators will measure the effect of energy availability on exercise performance during baseline, after 4 weeks of intensified training, and after a 2-week recovery, by measuring the relationship of energy availability to maximal oxygen consumption (VO2max) and 3200 meter time trial performance. The investigators will test the hypothesis that performance will be affected by changes in energy availability in a dose-dependent fashion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ovarian function</measure>
    <time_frame>Baseline (week 4), after 4 weeks of intensified training (week 8) and after a two-week recovery period (week 10)</time_frame>
    <description>The investigators will measure salivary estradiol and progesterone concentrations daily throughout the study, in order to test the hypothesis that ovarian function may be suppressed by intensified training and decreased energy availability.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in bone turnover markers</measure>
    <time_frame>Baseline (week 4), after 4 weeks of intensified training (week 8) and after a two-week recovery period (week 10)</time_frame>
    <description>The investigators will measure plasma bone turnover markers during baseline and at the end of the intensified training period, in order to test the hypothesis that bone turnover may be compromised by intensified training and decreased energy availability.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Amenorrhea</condition>
  <arm_group>
    <arm_group_label>Intensified training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Volunteers will increase exercise training by 30% from baseline</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Intensified Training</intervention_name>
    <description>Volunteers will increase exercise training by 30% from baseline</description>
    <arm_group_label>Intensified training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  competitive endurance runners (racing in events ranging from 10km to ultra-marathons)&#xD;
&#xD;
          -  training at least 5 days per week over the past 12 months, and more than 30 miles per&#xD;
             week&#xD;
&#xD;
          -  regular menstrual cycles (24-35 days) over the past 6 months&#xD;
&#xD;
          -  maximal oxygen consumption (VO2max) &gt; 50ml/kg/min&#xD;
&#xD;
          -  English speaking&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  smoker&#xD;
&#xD;
          -  amenorrhea&#xD;
&#xD;
          -  pregnant or lactating in the past 2 years&#xD;
&#xD;
          -  chronic disease that will affect bone health, metabolism or the cardiorespiratory&#xD;
             system&#xD;
&#xD;
          -  take medications that have cardiovascular or metabolic effects&#xD;
&#xD;
          -  present any contra-indication to exercise testing (cardiovascular abnormalities)&#xD;
&#xD;
          -  report any major illness or injury preventing training for more than 4 weeks over the&#xD;
             past 3 months&#xD;
&#xD;
          -  a history of clinical anorexia nervosa or bulimia nervosa&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gretchen A Casazza, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Davis</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USDA Western Human Nutrition Research Center</name>
      <address>
        <city>Davis</city>
        <state>California</state>
        <zip>95616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.ars.usda.gov/Main/docs.htm?docid=11240</url>
    <description>USDA Western Human Nutrition Research Center</description>
  </link>
  <link>
    <url>http://www.ucdmc.ucdavis.edu/sportsmedicine</url>
    <description>UC Davis Sports Medicine</description>
  </link>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>August 21, 2014</study_first_submitted>
  <study_first_submitted_qc>August 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 25, 2014</study_first_posted>
  <last_update_submitted>January 26, 2016</last_update_submitted>
  <last_update_submitted_qc>January 26, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>exercise training</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Amenorrhea</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02224976
org study id: FL94
nct id: NCT02224976
lead sponsor: 
collaborator: 
has dmc: No
The investigators propose a prospective, longitudinal, department funded study protocol to
      evaluate whether changes in energy availability, during a period of highly intensified
      exercise training, will increase bone turnover markers and decrease ovarian function and
      exercise performance, in a dose-dependent fashion in competitive female athletes.
Female athletes participating in sports which emphasize leanness as a factor to success,
      while also imposing large exercise training loads, present a high prevalence of endocrine and
      metabolic alterations linked to low energy stores, including suppressed ovarian function and
      bone loss. Increased bone turnover resulting from low energy stores and suppressed estrogen
      production may hold the most adverse consequences for long term health, increasing the risk
      of premature osteopenia, while increasing the risk of stress fractures in the short term.
      Chronically low energy stores may also contribute to the development of overreaching and
      overtraining syndromes, characterized by excessive, lasting fatigue and long-term decreases
      in performance, which can compromise these athletes' health and athletic career. The
      investigators propose the first longitudinal study aiming to demonstrate the link between low
      energy status, impaired ovarian function, bone turnover and decreased performance in
      free-living, competitive female athletes. After a 4-week baseline period of habitual
      training, athletes will undergo 4 weeks of intensified training (IT), during which the
      exercise load is increased by 30% from their individual baseline load in order to sharply
      increase energy expenditure. As athletes will be let to freely adjust their food intake, the
      investigators aim to test the hypothesis that athletes will fail to adjust food intake
      sufficiently to match energy expenditure, and that the resulting decrease in energy
      availability (EA, energy intake - energy expenditure from exercise) will influence, in a
      dose-dependent fashion, the suppression of estrogen production, the increase in bone turnover
      and the severity of performance decrement. The IT period will then be followed by a 2-week
      taper (REC), in which exercise training volume will be reduced by 50% from baseline. The
      investigators will assess whether EA returns to baseline values, and characterize changes in
      bone turnover during this recovery period. It is hypothesized that any improvements in
      exercise performance resulting from IT + REC will occur in athletes who were able to remain
      closest to a balanced energy state during IT. Concretely linking EA to both performance and
      bone health may incentivize female athletes to adopt more adequate feeding behaviors for
      their activity level.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in energy availability (energy intake - energy expenditure of physical activity)
time frame: Baseline (week 4), after 4 weeks of intensified training (week 8) and after a two-week recovery period (week 10)
description: The investigators aim to capture the spectrum and variability of energy availability in endurance athletes under normal training conditions, describing in detail training regimen, total energy expenditure and nutrition habits during three distinct phases of training that are habitually followed by endurance athletes.
measure: Change in athletic performance
time frame: Baseline (week 4), after 4 weeks of intensified training (week 8) and after a two-week recovery period (week 10)
description: The investigators will measure the effect of energy availability on exercise performance during baseline, after 4 weeks of intensified training, and after a 2-week recovery, by measuring the relationship of energy availability to maximal oxygen consumption (VO2max) and 3200 meter time trial performance. The investigators will test the hypothesis that performance will be affected by changes in energy availability in a dose-dependent fashion.
measure: Change in ovarian function
time frame: Baseline (week 4), after 4 weeks of intensified training (week 8) and after a two-week recovery period (week 10)
description: The investigators will measure salivary estradiol and progesterone concentrations daily throughout the study, in order to test the hypothesis that ovarian function may be suppressed by intensified training and decreased energy availability.
measure: Change in bone turnover markers
time frame: Baseline (week 4), after 4 weeks of intensified training (week 8) and after a two-week recovery period (week 10)
description: The investigators will measure plasma bone turnover markers during baseline and at the end of the intensified training period, in order to test the hypothesis that bone turnover may be compromised by intensified training and decreased energy availability.
arm group label: Intensified training
arm group type: Experimental
description: Volunteers will increase exercise training by 30% from baseline
intervention type: Behavioral
intervention name: Intensified Training
description: Volunteers will increase exercise training by 30% from baseline
arm group label: Intensified training
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gretchen A Casazza, PhD
role: Principal Investigator
affiliation: University of California, Davis
facility: 
country: United States
url: http://www.ars.usda.gov/Main/docs.htm?docid=11240
description: USDA Western Human Nutrition Research Center
url: http://www.ucdmc.ucdavis.edu/sportsmedicine
description: UC Davis Sports Medicine
responsible party type: Sponsor
mesh term: Amenorrhea
sharing ipd: Undecided