<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/NCT01723748</url>
  </required_header>
  <id_info>
    <org_study_id>1-10-72-491-12</org_study_id>
    <secondary_id>35197</secondary_id>
    <nct_id>NCT01723748</nct_id>
  </id_info>
  <brief_title>Somatostatin Analogue Treatment of Acromegaly: Molecular Aspects</brief_title>
  <official_title>Somatostatin Analogue Treatment of Acromegaly: Molecular Aspects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Aarhus</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Aarhus</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The treatment with SA still leaves some questions unanswered. Firstly, SA treatment often&#xD;
      results in a concomitant suppression of the insulin secretion, which might lead to clinically&#xD;
      significant glucose intolerance. Secondly, the traditional evaluation of disease activity by&#xD;
      measuring circulating levels of GH and total IGF-I is not reliable enough&#xD;
&#xD;
      Hypotheses: Treatment of acromegaly with SA versus surgery alone is associated with:&#xD;
&#xD;
        -  Glucose intolerance despite normalized insulin sensitivity&#xD;
&#xD;
        -  Modified peripheral GH activity in peripheral target organs assessed on molecular&#xD;
           endpoints&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Acromegaly is a rare disease usually caused by a benign growth hormone (GH) producing&#xD;
      pituitary adenoma. In case of inadequate disease control, the condition is associated with&#xD;
      significant morbidity and approximately a doubling of mortality compared to the background&#xD;
      population. Medical treatment with somatostatin analogues (SA) has been employed for about 20&#xD;
      years and is a well-established treatment in cases where surgery is impossible or inadequate.&#xD;
      The treatment with SA still leaves some questions unanswered. Firstly, SA treatment often&#xD;
      results in a concomitant suppression of the insulin secretion, which might lead to clinically&#xD;
      significant glucose intolerance. Secondly, the traditional evaluation of disease activity by&#xD;
      measuring circulating levels of GH and total IGF-I is not reliable enough&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Metabolism - including GH, IGF-I, FFA, glc and insulin. Concentration and AUC (area under the curve)</measure>
    <time_frame>3 years</time_frame>
    <description>GH (ug/l), IGF-I (ug/l), FFA (mmol/l) , glc (mmol/l) and insulin (pmol/l)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>concentration of serum and interstitial GH, bioactive IGF-I as well as total IGF-I</measure>
    <time_frame>3 years</time_frame>
    <description>GH (ug/l), IGF-l (ug/l), bioactive IGF-l (ug/l)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>GH, and insulin signal transduction in muscle and fat biopsies and regulation of lipolysis.</measure>
    <time_frame>3 years</time_frame>
    <description>By western blot technique protien levels of (arbitrary densitomety units) AKT, pAKT threonin, pAKT serine, STAT5, pSTAT5, PTEN, p85alpha, mTOR, pmTOR.&#xD;
By PCR technique (relative nRNA expression) mRNA levels of IGF-1, SOCS1, SOCS2, SOCS3, CISH, PTEN, Pik3r</description>
  </other_outcome>
  <other_outcome>
    <measure>patient characterization</measure>
    <time_frame>3 years</time_frame>
    <description>sex (M/F), age (year), disease duration (years), BMI (kg/m2)</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Acromegaly</condition>
  <condition>Metabolic Diseases</condition>
  <arm_group>
    <arm_group_label>surgery treated</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>10 patients with well-controlled acromegaly for at least 6 months after surgery alone.&#xD;
Stimulated with genotropin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SA treated</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>10 patients with well-controlled acromegaly for at least 6 months after SA treatment Stimulated with genotropin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>genotropin</intervention_name>
    <description>iii) intravenous exogenous bolus of GH (0.5 mg) followed by muscle and fat biopsies.</description>
    <arm_group_label>SA treated</arm_group_label>
    <arm_group_label>surgery treated</arm_group_label>
    <other_name>growth hormone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  &gt; 18 years&#xD;
&#xD;
          -  treated acromegaly&#xD;
&#xD;
          -  considered suitable&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jens Otto L Joergensen, professor</last_name>
    <role>Study Director</role>
    <affiliation>Aarhus University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aarhus University Hospital</name>
      <address>
        <city>Aarhus</city>
        <zip>8000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>December 2014</verification_date>
  <study_first_submitted>November 6, 2012</study_first_submitted>
  <study_first_submitted_qc>November 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 8, 2012</study_first_posted>
  <last_update_submitted>April 4, 2016</last_update_submitted>
  <last_update_submitted_qc>April 4, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acromegaly</keyword>
  <keyword>Somatostatin treatment</keyword>
  <keyword>metabolic effect</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acromegaly</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hormones</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/NCT01723748
org study id: 1-10-72-491-12
secondary id: 35197
nct id: NCT01723748
lead sponsor: 
has dmc: Yes
The treatment with SA still leaves some questions unanswered. Firstly, SA treatment often
      results in a concomitant suppression of the insulin secretion, which might lead to clinically
      significant glucose intolerance. Secondly, the traditional evaluation of disease activity by
      measuring circulating levels of GH and total IGF-I is not reliable enough

      Hypotheses: Treatment of acromegaly with SA versus surgery alone is associated with:

        -  Glucose intolerance despite normalized insulin sensitivity

        -  Modified peripheral GH activity in peripheral target organs assessed on molecular
           endpoints
Acromegaly is a rare disease usually caused by a benign growth hormone (GH) producing
      pituitary adenoma. In case of inadequate disease control, the condition is associated with
      significant morbidity and approximately a doubling of mortality compared to the background
      population. Medical treatment with somatostatin analogues (SA) has been employed for about 20
      years and is a well-established treatment in cases where surgery is impossible or inadequate.
      The treatment with SA still leaves some questions unanswered. Firstly, SA treatment often
      results in a concomitant suppression of the insulin secretion, which might lead to clinically
      significant glucose intolerance. Secondly, the traditional evaluation of disease activity by
      measuring circulating levels of GH and total IGF-I is not reliable enough
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Metabolism - including GH, IGF-I, FFA, glc and insulin. Concentration and AUC (area under the curve)
time frame: 3 years
description: GH (ug/l), IGF-I (ug/l), FFA (mmol/l) , glc (mmol/l) and insulin (pmol/l)
measure: concentration of serum and interstitial GH, bioactive IGF-I as well as total IGF-I
time frame: 3 years
description: GH (ug/l), IGF-l (ug/l), bioactive IGF-l (ug/l)
measure: GH, and insulin signal transduction in muscle and fat biopsies and regulation of lipolysis.
time frame: 3 years
description: By western blot technique protien levels of (arbitrary densitomety units) AKT, pAKT threonin, pAKT serine, STAT5, pSTAT5, PTEN, p85alpha, mTOR, pmTOR.
By PCR technique (relative nRNA expression) mRNA levels of IGF-1, SOCS1, SOCS2, SOCS3, CISH, PTEN, Pik3r
measure: patient characterization
time frame: 3 years
description: sex (M/F), age (year), disease duration (years), BMI (kg/m2)
arm group label: surgery treated
arm group type: Active Comparator
description: 10 patients with well-controlled acromegaly for at least 6 months after surgery alone.
Stimulated with genotropin
arm group label: SA treated
arm group type: Active Comparator
description: 10 patients with well-controlled acromegaly for at least 6 months after SA treatment Stimulated with genotropin
intervention type: Drug
intervention name: genotropin
description: iii) intravenous exogenous bolus of GH (0.5 mg) followed by muscle and fat biopsies.
arm group label: SA treated
arm group label: surgery treated
other name: growth hormone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Jens Otto L Joergensen, professor
role: Study Director
affiliation: Aarhus University Hospital
facility: 
country: Denmark
responsible party type: Sponsor
mesh term: Acromegaly
mesh term: Metabolic Diseases
mesh term: Hormones
sharing ipd: No