<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/NCT03227458</url>
  </required_header>
  <id_info>
    <org_study_id>16-2427</org_study_id>
    <secondary_id>R01AG053489</secondary_id>
    <nct_id>NCT03227458</nct_id>
  </id_info>
  <brief_title>DHEA Augmentation of Musculoskeletal Adaptations to Exercise in Older Women</brief_title>
  <official_title>DHEA Augmentation of Musculoskeletal Adaptations to Exercise in Older Women</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Aging (NIA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Colorado, Denver</source>
  <oversight_info>
    <has_dmc>Yes</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>
      To determine whether the musculoskeletal adaptations to bone-loading exercise can be&#xD;
      significantly augmented in older women (aged 60-85) with low bone mass (osteopenia; T-scores&#xD;
      &lt;-1.0 and &gt;-2.5) or moderate osteoporosis (T-scores &lt; -2.5 and &gt;= -3.0) and by restoring&#xD;
      serum DHEAS to young adult levels by oral DHEA replacement.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This will be the first study to measure changes in areal bone mineral density (aBMD) and&#xD;
      fat-free mass (FFM) in response to dehydroepiandrosterone (DHEA) alone and combined with&#xD;
      exercise in postmenopausal women. The body of evidence from carefully executed Randomized&#xD;
      Controlled Studies (RCTs) provides support for DHEA therapy to increase aBMD and FFM in older&#xD;
      women. Less is known about whether DHEA therapy enhances the effects of exercise on the aging&#xD;
      musculoskeletal system when an appropriate mechanical stimulus is applied.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 12, 2018</start_date>
  <completion_date type="Anticipated">April 2024</completion_date>
  <primary_completion_date type="Anticipated">April 2024</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>All participants will take 1 study pill (50 mg DHEA or placebo: double-blinded) daily for 36 weeks. The research pharmacist will dispense study drug according to the randomization code and maintain drug dispensation records, which will be monitored by the study biostatistician. Two-thirds of participants will engage in bone-loading exercise 3 days per week for the 36 weeks.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Study drug will be masked. 50 mg DHEA or placebo: double-blinded. Exercise will not be masked.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in lumbar spine aBMD</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in lumbar spine aBMD</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in total hip aBMD</measure>
    <time_frame>36 Weeks</time_frame>
    <description>mean change from baseline in total hip aBMD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in regional hip aBMD</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in regional hip aBMD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Vertebral (L1-2) total volumetric bone mineral density (vBMD)</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in vertebral total volumetric BMD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Vertebral (L1-2) cortical vBMD</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in vertebral cortical volumetric BMD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Vertebral (L1-2) trabecular vBMD</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in vertebral trabecular volumetric BMD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Femoral total vBMD</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in femoral total volumetric BMD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Femoral cortical vBMD</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in femoral cortical volumetric BMD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Femoral trabecular vBMD</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in femoral trabecular volumetric BMD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Vertebral (L1-2) strength, stance model</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in the estimated strength of L1-2 vertebrae in a stance model</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Vertebral (L1-2) strength, fall model</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in the estimated strength of L1-2 vertebrae in a fall model</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Proximal femur strength, stance model</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in the estimated strength of the proximal femur in a stance model</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Proximal femur strength, fall model</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in the estimated strength of the proximal femur in a fall model</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Total body fat-free mass</measure>
    <time_frame>Baseline and 36 Weeks</time_frame>
    <description>mean change from baseline in total body fat-free mass</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">225</enrollment>
  <condition>Low Bone Mass</condition>
  <condition>Osteoporosis, Postmenopausal</condition>
  <arm_group>
    <arm_group_label>Exercise and DHEA</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 study pill containing 50 mg of DHEA daily for 36 weeks and supervised bone-loading exercise on 3 days per week for 36 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exercise and Placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 study pill containing placebo daily for 36 weeks and supervised bone-loading exercise on 3 days per week for 36 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DHEA only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 study pill containing 50 mg of DHEA daily for 36 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>DHEA</intervention_name>
    <description>Participants will take 1 study pill (50 mg DHEA) daily for 36 weeks.</description>
    <arm_group_label>DHEA only</arm_group_label>
    <arm_group_label>Exercise and DHEA</arm_group_label>
    <other_name>DHEA therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will take placebo daily for 36 weeks.</description>
    <arm_group_label>Exercise and Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Exercise</intervention_name>
    <description>bone-loading exercise on 3 days per week for 38 weeks</description>
    <arm_group_label>Exercise and DHEA</arm_group_label>
    <arm_group_label>Exercise and Placebo</arm_group_label>
    <other_name>bone-loading exercise</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  non-frail, as determined by short physical performance battery (SPPB) score &gt; 9 (0-12&#xD;
             scale);&#xD;
&#xD;
          -  5 years or longer since menopause (defined as last menstrual period);&#xD;
&#xD;
          -  willing to participate in a 36-week exercise program that will start at a moderate&#xD;
             intensity and gradually progress to a higher intensity;&#xD;
&#xD;
          -  willing to be randomized to an exercise or a no-exercise arm of the study;&#xD;
&#xD;
          -  willing to take DHEA (50mg/d) or a placebo pill daily and remain blinded for up to 36&#xD;
             weeks;&#xD;
&#xD;
          -  not performing resistance exercise training or high impact weight-bearing exercise&#xD;
             (e.g., jogging) ≥ 2 days per week in the past 6 months;&#xD;
&#xD;
          -  ambulatory without assistive devices;&#xD;
&#xD;
          -  serum DHEAS &lt; 140 μg/dL (3.8 μmol/L);&#xD;
&#xD;
          -  low bone mass or moderate osteoporosis defined as lumbar spine or proximal hip aBMD&#xD;
             t-scores &lt; -1.0 and &gt; = -3.0;&#xD;
&#xD;
          -  refusal of standard osteoporosis treatment in women with moderate osteoporosis (BMD&#xD;
             t-scores &gt;=-3.0 and =&lt; 2.5).&#xD;
&#xD;
          -  evidence of a negative (no findings suspicious for breast cancer) mammogram within the&#xD;
             past 12 months;&#xD;
&#xD;
          -  planning to reside in the Denver area for the duration of the study&#xD;
&#xD;
          -  normal cognitive function, as determined by a Mini-Cog score &gt; = 4&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  history of hospitalization for Corona Virus Disease-19 (COVID-19)&#xD;
&#xD;
          -  does not meet Centers for Disease Control and Prevention (CDC) recommendations for&#xD;
             home isolation because has had a positive severe acute respiratory syndrome corona&#xD;
             virus-2 (SARS-COV-2) test less than 10 days before study entry; or has had fever&#xD;
             within the past 3 days and respiratory symptoms have not improved; or symptoms first&#xD;
             appeared less than 10 days before study entry&#xD;
&#xD;
          -  uncontrolled hypertension defined as resting systolic blood pressure (sBP) &gt;150 mmHg&#xD;
             or diastolic blood pressure (dBP) &gt;90 mmHg; participants who do not meet these&#xD;
             criteria at first screening will be re-evaluated, including follow-up evaluation by&#xD;
             their Primary Care Physician (PCP) with initiation or adjustment of anti-hypertensive&#xD;
             medications;&#xD;
&#xD;
          -  diagnosed ischemic heart disease or indicators of unstable ischemic heart disease&#xD;
             (e.g., angina, ST segment depression) or arrhythmias at rest or during the Gated&#xD;
             Exercise Test (GXT) without negative follow-up evaluation will be cause for exclusion;&#xD;
             follow-up evaluation must include diagnostic testing (e.g., thallium stress test) with&#xD;
             interpretation by a cardiologist;&#xD;
&#xD;
          -  diagnosis of heart failure, clinically significant aortic stenosis, uncontrolled&#xD;
             angina, or uncontrolled arrhythmia.&#xD;
&#xD;
          -  pulmonary disease requiring use of oral steroids within the previous 6 months or the&#xD;
             use of supplemental oxygen ≥ 4 liters with physical exertion&#xD;
&#xD;
          -  orthopedic problems (e.g., severe osteoarthritis, rheumatoid arthritis) that greatly&#xD;
             limit the ability to perform moderate to high intensity resistance exercise (e.g.,&#xD;
             unable to be properly positioned in exercise equipment or to have severely restricted&#xD;
             range of motion even after modifications have been made)&#xD;
&#xD;
          -  hip fracture, hip or knee replacement, or spinal surgery in the past 6 months;&#xD;
&#xD;
          -  undergoing physical therapy involving the lower extremities;&#xD;
&#xD;
          -  hematocrit (HCT) &gt; 54%;&#xD;
&#xD;
          -  thyroid dysfunction, defined as an ultrasensitive thyroid stimulating hormone (TSH) &lt;&#xD;
             0.4 or &gt; 10.0 microunits/mL;, without signs or symptoms of clinical hypo- or&#xD;
             hyperthyroidism. Volunteers with abnormal TSH values will be re-considered for&#xD;
             participation in the study after follow-up evaluation by their PCP with initiation or&#xD;
             adjustment of thyroid hormone replacement;&#xD;
&#xD;
          -  acute liver disease indicated by liver function tests (alanine aminotransferase (ALT),&#xD;
             aspartate aminotransferase (AST), alkaline phosphatase) ≥ 1.5 times the upper limits&#xD;
             of normal;&#xD;
&#xD;
          -  estimated glomerular filtration rate (eGFR) &lt; 45, using the Modification of Diet in&#xD;
             Renal Disease (MDRD) equation (Levey et al, Annals Inter Med, 1999; Munter et al, Clin&#xD;
             J Am Soc Nephrology, 2009);&#xD;
&#xD;
          -  poorly controlled diabetes mellitus based on HbA1c &gt; 8.5%, or use of insulin;&#xD;
&#xD;
          -  fasted serum triglycerides &gt; 400 mg/dL;&#xD;
&#xD;
          -  serum 25-hydroxy vitamin D &lt;20 ng/mL; volunteers will be re-considered for&#xD;
             participation in the study after follow-up evaluation by their PCP with initiation or&#xD;
             adjustment of vitamin D supplementation per the study's vitamin D repletion protocol.&#xD;
&#xD;
          -  use of DHEA supplementation or sex hormones in the past 6 months. Use of prescription&#xD;
             low dose vaginal estrogen creams (Premarin or Estrace) 3 days per week will not be&#xD;
             exclusionary.&#xD;
&#xD;
          -  use in the past 6 months of any medications known to alter bone metabolism (e.g., oral&#xD;
             glucocorticoids, bone anti-resorptive agents);&#xD;
&#xD;
          -  documented history of cognitive impairment or dementia, or Mini-Cog &lt; 4;&#xD;
&#xD;
          -  current smoker;&#xD;
&#xD;
          -  personal history of breast, ovarian, metastatic endometrial, or cervical cancer;&#xD;
&#xD;
          -  any cancer requiring treatment in the past 3 years except non-melanoma skin cancers;&#xD;
&#xD;
          -  un-diagnosed vaginal bleeding;&#xD;
&#xD;
          -  women who, in the judgment of the study physician, appear incapable of safely&#xD;
             participating in the exercise (e.g., neuromuscular/musculoskeletal impairment)&#xD;
&#xD;
          -  use of insulin;&#xD;
&#xD;
          -  lumbar spine, total hip, or femoral neck aBMD t-scores &lt; -3.0;&#xD;
&#xD;
          -  secondary osteoporosis&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>55 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Catherine Jankowski, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Colorado, Denver</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Catherine Jankowski, PhD</last_name>
    <phone>303-724-7383</phone>
    <email>catherine.jankowski@cuanschutz.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Colorado Anschutz Medical Campus</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Catherine Jankowski, PhD</last_name>
      <phone>303-724-7383</phone>
      <email>catherine.jankowski@cuanschutz.edu</email>
    </contact>
    <investigator>
      <last_name>Catherine Jankowski, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>July 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2017</study_first_posted>
  <last_update_submitted>March 13, 2023</last_update_submitted>
  <last_update_submitted_qc>March 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>areal bone mineral density</keyword>
  <keyword>dehydroepiandrosterone (DHEA)</keyword>
  <keyword>postmenopause</keyword>
  <keyword>exercise</keyword>
  <keyword>sex hormones</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</mesh_term>
    <mesh_term>Osteoporosis, Postmenopausal</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dehydroepiandrosterone</mesh_term>
  </intervention_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/NCT03227458
org study id: 16-2427
secondary id: R01AG053489
nct id: NCT03227458
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To determine whether the musculoskeletal adaptations to bone-loading exercise can be
      significantly augmented in older women (aged 60-85) with low bone mass (osteopenia; T-scores
      <-1.0 and >-2.5) or moderate osteoporosis (T-scores < -2.5 and >= -3.0) and by restoring
      serum DHEAS to young adult levels by oral DHEA replacement.
This will be the first study to measure changes in areal bone mineral density (aBMD) and
      fat-free mass (FFM) in response to dehydroepiandrosterone (DHEA) alone and combined with
      exercise in postmenopausal women. The body of evidence from carefully executed Randomized
      Controlled Studies (RCTs) provides support for DHEA therapy to increase aBMD and FFM in older
      women. Less is known about whether DHEA therapy enhances the effects of exercise on the aging
      musculoskeletal system when an appropriate mechanical stimulus is applied.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: All participants will take 1 study pill (50 mg DHEA or placebo: double-blinded) daily for 36 weeks. The research pharmacist will dispense study drug according to the randomization code and maintain drug dispensation records, which will be monitored by the study biostatistician. Two-thirds of participants will engage in bone-loading exercise 3 days per week for the 36 weeks.
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
masking description: Study drug will be masked. 50 mg DHEA or placebo: double-blinded. Exercise will not be masked.
measure: Change in lumbar spine aBMD
time frame: Baseline and 36 Weeks
description: mean change from baseline in lumbar spine aBMD
measure: Change in total hip aBMD
time frame: 36 Weeks
description: mean change from baseline in total hip aBMD
measure: Change in regional hip aBMD
time frame: Baseline and 36 Weeks
description: mean change from baseline in regional hip aBMD
measure: Change in Vertebral (L1-2) total volumetric bone mineral density (vBMD)
time frame: Baseline and 36 Weeks
description: mean change from baseline in vertebral total volumetric BMD
measure: Change in Vertebral (L1-2) cortical vBMD
time frame: Baseline and 36 Weeks
description: mean change from baseline in vertebral cortical volumetric BMD
measure: Change in Vertebral (L1-2) trabecular vBMD
time frame: Baseline and 36 Weeks
description: mean change from baseline in vertebral trabecular volumetric BMD
measure: Change in Femoral total vBMD
time frame: Baseline and 36 Weeks
description: mean change from baseline in femoral total volumetric BMD
measure: Change in Femoral cortical vBMD
time frame: Baseline and 36 Weeks
description: mean change from baseline in femoral cortical volumetric BMD
measure: Change in Femoral trabecular vBMD
time frame: Baseline and 36 Weeks
description: mean change from baseline in femoral trabecular volumetric BMD
measure: Change in Vertebral (L1-2) strength, stance model
time frame: Baseline and 36 Weeks
description: mean change from baseline in the estimated strength of L1-2 vertebrae in a stance model
measure: Change in Vertebral (L1-2) strength, fall model
time frame: Baseline and 36 Weeks
description: mean change from baseline in the estimated strength of L1-2 vertebrae in a fall model
measure: Change in Proximal femur strength, stance model
time frame: Baseline and 36 Weeks
description: mean change from baseline in the estimated strength of the proximal femur in a stance model
measure: Change in Proximal femur strength, fall model
time frame: Baseline and 36 Weeks
description: mean change from baseline in the estimated strength of the proximal femur in a fall model
measure: Change in Total body fat-free mass
time frame: Baseline and 36 Weeks
description: mean change from baseline in total body fat-free mass
arm group label: Exercise and DHEA
arm group type: Active Comparator
description: 1 study pill containing 50 mg of DHEA daily for 36 weeks and supervised bone-loading exercise on 3 days per week for 36 weeks.
arm group label: Exercise and Placebo
arm group type: Active Comparator
description: 1 study pill containing placebo daily for 36 weeks and supervised bone-loading exercise on 3 days per week for 36 weeks.
arm group label: DHEA only
arm group type: Active Comparator
description: 1 study pill containing 50 mg of DHEA daily for 36 weeks
intervention type: Other
intervention name: DHEA
description: Participants will take 1 study pill (50 mg DHEA) daily for 36 weeks.
arm group label: DHEA only
arm group label: Exercise and DHEA
other name: DHEA therapy
intervention type: Other
intervention name: Placebo
description: Participants will take placebo daily for 36 weeks.
arm group label: Exercise and Placebo
intervention type: Behavioral
intervention name: Exercise
description: bone-loading exercise on 3 days per week for 38 weeks
arm group label: Exercise and DHEA
arm group label: Exercise and Placebo
other name: bone-loading exercise
criteria: 
gender: Female
minimum age: 55 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Catherine Jankowski, PhD
role: Principal Investigator
affiliation: University of Colorado, Denver
last name: Catherine Jankowski, PhD
phone: 303-724-7383
email: catherine.jankowski@cuanschutz.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Osteoporosis
mesh term: Osteoporosis, Postmenopausal
mesh term: Dehydroepiandrosterone
sharing ipd: No