<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/NCT03800290</url>
  </required_header>
  <id_info>
    <org_study_id>NL67646.068.18</org_study_id>
    <nct_id>NCT03800290</nct_id>
  </id_info>
  <brief_title>Human Beta-2 Adrenergic Stimulation and Muscle Glucose Uptake</brief_title>
  <official_title>Targeting the Beta-2-adrenergic Pathway to Improve Skeletal Muscle Glucose Uptake in Healthy Humans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the effect of two weeks clenbuterol/placebo&#xD;
      supplementation on skeletal muscle glucose disposal in healthy male volunteers.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 1, 2019</start_date>
  <completion_date type="Actual">April 23, 2021</completion_date>
  <primary_completion_date type="Actual">April 23, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Randomized, double-blinded, placebo-controlled, cross-over, single-center study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin-stimulated peripheral glucose disposal (Rd)</measure>
    <time_frame>2 weeks</time_frame>
    <description>Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on insulin-stimulated peripheral glucose disposal (Rd) during the high-insulin infusion step during the two-step hyperinsulinemic-euglycemic clamp.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Skeletal muscle GLUT4 translocation</measure>
    <time_frame>acute (4 hours) and long-term (2 weeks)</time_frame>
    <description>Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle GLUT4 translocation as assessed by means of wide-field microscopy in skeletal muscle biopsies</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Body weight/composition</measure>
    <time_frame>2 weeks</time_frame>
    <description>Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on body weight and composition as assessed by means of a Bodpod measurement.</description>
  </other_outcome>
  <other_outcome>
    <measure>Plasma substrates</measure>
    <time_frame>Acute (4 hours) and long-term (1 and 2 weeks)</time_frame>
    <description>Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on plasma substrate concentrations, including insulin, glucose, free fatty acids and TAGs.</description>
  </other_outcome>
  <other_outcome>
    <measure>Heart rate</measure>
    <time_frame>Acute (4 hours) and long-term (1 and 2 weeks)</time_frame>
    <description>Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on heart rate as measured by means of an automated cuff.</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood pressure</measure>
    <time_frame>Acute (4 hours) and long-term (1 and 2 weeks)</time_frame>
    <description>Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on blood pressure (systolic and diastolic) as measured by means of an automated cuff.</description>
  </other_outcome>
  <other_outcome>
    <measure>Insulin-mediated suppression of hepatic glucose production</measure>
    <time_frame>2 weeks</time_frame>
    <description>Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on hepatic glucose production as assessed during the two-step hyperinsulinemic-euglycemic clamp.</description>
  </other_outcome>
  <other_outcome>
    <measure>Energy expenditure and substrate oxidation</measure>
    <time_frame>Acute (4 hours) and long-term (2 weeks)</time_frame>
    <description>Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on energy expenditure and substrate oxidation as assessed by means of indirect calorimetry.</description>
  </other_outcome>
  <other_outcome>
    <measure>Sleeping energy expenditure and substrate oxidation</measure>
    <time_frame>2-weeks</time_frame>
    <description>Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on sleeping energy expenditure and substrate oxidation as assessed by means of a metabolic chamber (indirect calorimetry).</description>
  </other_outcome>
  <other_outcome>
    <measure>Skeletal muscle glycogen</measure>
    <time_frame>2 weeks</time_frame>
    <description>Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle glycogen as assessed in muscle biopsies.</description>
  </other_outcome>
  <other_outcome>
    <measure>Skeletal muscle lipid content using wide-field microscopie</measure>
    <time_frame>2 weeks</time_frame>
    <description>Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle lipid content as assessed in muscle biopsies by wide-field microscopie.</description>
  </other_outcome>
  <other_outcome>
    <measure>Skeletal muscle gene expression</measure>
    <time_frame>Acute (4 hours) and long-term (1 and 2 weeks)</time_frame>
    <description>Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle gene expression of specific pathways as determined in muscle biopsies by means of RT-qPCR</description>
  </other_outcome>
  <other_outcome>
    <measure>Skeletal muscle protein expression using western blotting</measure>
    <time_frame>Acute (4 hours) and long-term (1 and 2 weeks)</time_frame>
    <description>Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle protein expression of specific pathways as determined in muscle biopsies as determined by means of Western Blotting</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Clenbuterol hydrochloride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will ingest clenbuterol hydrochloride capsules (20 microgram/each) twice daily (40 microgram/day) for a maximum of 14 days.&#xD;
Subjects that received the clenbuterol hydrochloride capsules (at random) in the first study period will receive the placebo capsules during the second study period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebos</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will ingest placebo capsules matching the clenbuterol hydrochloride capsules one time per day for a maximum of 14 days.&#xD;
Subjects that received the placebo capsules (at random) in the first study period will receive the clenbuterol hydrochloride capsules during the second study period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clenbuterol Hydrochloride</intervention_name>
    <description>Daily ingestion of clenbuterol hydrochloride capsules (40 microgram/day) for a total period of 14 days with a wash-out period of 4 weeks.</description>
    <arm_group_label>Clenbuterol hydrochloride</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>Daily ingestion of placebo capsules for a total period of 14 days with a wash-out period of 4 weeks.</description>
    <arm_group_label>Placebos</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Caucasian;&#xD;
&#xD;
          2. Male sex;&#xD;
&#xD;
          3. Age: 18-30&#xD;
&#xD;
          4. BMI: 18-25 kg/m2;&#xD;
&#xD;
          5. Normal physical activity levels;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Not meeting all inclusion criteria&#xD;
&#xD;
          2. Cardiovascular diseases (determined by means of questionnaires, heart rate/blood&#xD;
             pressure measurements)&#xD;
&#xD;
          3. Respiratory diseases (including asthma, bronchitis and COPD);&#xD;
&#xD;
          4. Unstable body weight (weight gain or loss &gt; 5 kg in the last three months);&#xD;
&#xD;
          5. Intention to lose or gain body weight (e.g. with caloric restriction or physical&#xD;
             activity)&#xD;
&#xD;
          6. Excessive alcohol and/or drug abuse;&#xD;
&#xD;
          7. Hypokalaemia;&#xD;
&#xD;
          8. Hb &lt; 8.4 mmol/L;&#xD;
&#xD;
          9. Epilepsy;&#xD;
&#xD;
         10. Smoking;&#xD;
&#xD;
         11. Renal and/or liver insufficiency;&#xD;
&#xD;
         12. Participation in another biomedical study within 1 month before the first study visit,&#xD;
             possibly interfering with the study results;&#xD;
&#xD;
         13. Medication use known to hamper subject's safety during the study procedures;&#xD;
&#xD;
         14. Subjects who do not want to be informed about unexpected medical findings;&#xD;
&#xD;
         15. Subjects who do not want that their treating physician to be informed;&#xD;
&#xD;
         16. Inability to participate and/or complete the required measurements;&#xD;
&#xD;
         17. Participation in organised or structured physical exercise;&#xD;
&#xD;
         18. Any condition, disease or abnormal laboratory test result that, in the opinion of the&#xD;
             Investigator, would interfere with the study outcome, affect trial participation or&#xD;
             put the subject at undue risk;&#xD;
&#xD;
         19. Hyperthyroidism&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joris Hoeks, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>principle investigator</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6229ER</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>November 28, 2022</last_update_submitted>
  <last_update_submitted_qc>November 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Beta-2 adrenergic agonist</keyword>
  <keyword>Glucose homeostasis</keyword>
  <keyword>Skeletal muscle</keyword>
  <keyword>Human</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clenbuterol</mesh_term>
  </intervention_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/NCT03800290
org study id: NL67646.068.18
nct id: NCT03800290
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the effect of two weeks clenbuterol/placebo
      supplementation on skeletal muscle glucose disposal in healthy male volunteers.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Randomized, double-blinded, placebo-controlled, cross-over, single-center study
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Insulin-stimulated peripheral glucose disposal (Rd)
time frame: 2 weeks
description: Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on insulin-stimulated peripheral glucose disposal (Rd) during the high-insulin infusion step during the two-step hyperinsulinemic-euglycemic clamp.
measure: Skeletal muscle GLUT4 translocation
time frame: acute (4 hours) and long-term (2 weeks)
description: Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle GLUT4 translocation as assessed by means of wide-field microscopy in skeletal muscle biopsies
measure: Body weight/composition
time frame: 2 weeks
description: Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on body weight and composition as assessed by means of a Bodpod measurement.
measure: Plasma substrates
time frame: Acute (4 hours) and long-term (1 and 2 weeks)
description: Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on plasma substrate concentrations, including insulin, glucose, free fatty acids and TAGs.
measure: Heart rate
time frame: Acute (4 hours) and long-term (1 and 2 weeks)
description: Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on heart rate as measured by means of an automated cuff.
measure: Blood pressure
time frame: Acute (4 hours) and long-term (1 and 2 weeks)
description: Comparison between acute (4h) and prolonged (1 and 2 weeks) clenbuterol hydrochloride or placebo supplementation on blood pressure (systolic and diastolic) as measured by means of an automated cuff.
measure: Insulin-mediated suppression of hepatic glucose production
time frame: 2 weeks
description: Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on hepatic glucose production as assessed during the two-step hyperinsulinemic-euglycemic clamp.
measure: Energy expenditure and substrate oxidation
time frame: Acute (4 hours) and long-term (2 weeks)
description: Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on energy expenditure and substrate oxidation as assessed by means of indirect calorimetry.
measure: Sleeping energy expenditure and substrate oxidation
time frame: 2-weeks
description: Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on sleeping energy expenditure and substrate oxidation as assessed by means of a metabolic chamber (indirect calorimetry).
measure: Skeletal muscle glycogen
time frame: 2 weeks
description: Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle glycogen as assessed in muscle biopsies.
measure: Skeletal muscle lipid content using wide-field microscopie
time frame: 2 weeks
description: Comparison between prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle lipid content as assessed in muscle biopsies by wide-field microscopie.
measure: Skeletal muscle gene expression
time frame: Acute (4 hours) and long-term (1 and 2 weeks)
description: Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle gene expression of specific pathways as determined in muscle biopsies by means of RT-qPCR
measure: Skeletal muscle protein expression using western blotting
time frame: Acute (4 hours) and long-term (1 and 2 weeks)
description: Comparison between acute (4h) and prolonged (2 weeks) clenbuterol hydrochloride or placebo supplementation on skeletal muscle protein expression of specific pathways as determined in muscle biopsies as determined by means of Western Blotting
arm group label: Clenbuterol hydrochloride
arm group type: Experimental
description: Subjects will ingest clenbuterol hydrochloride capsules (20 microgram/each) twice daily (40 microgram/day) for a maximum of 14 days.
Subjects that received the clenbuterol hydrochloride capsules (at random) in the first study period will receive the placebo capsules during the second study period.
arm group label: Placebos
arm group type: Placebo Comparator
description: Subjects will ingest placebo capsules matching the clenbuterol hydrochloride capsules one time per day for a maximum of 14 days.
Subjects that received the placebo capsules (at random) in the first study period will receive the clenbuterol hydrochloride capsules during the second study period.
intervention type: Drug
intervention name: Clenbuterol Hydrochloride
description: Daily ingestion of clenbuterol hydrochloride capsules (40 microgram/day) for a total period of 14 days with a wash-out period of 4 weeks.
arm group label: Clenbuterol hydrochloride
intervention type: Drug
intervention name: Placebos
description: Daily ingestion of placebo capsules for a total period of 14 days with a wash-out period of 4 weeks.
arm group label: Placebos
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Joris Hoeks, PhD
role: Principal Investigator
affiliation: principle investigator
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Clenbuterol