<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/NCT03809793</url>
  </required_header>
  <id_info>
    <org_study_id>250408</org_study_id>
    <nct_id>NCT03809793</nct_id>
  </id_info>
  <brief_title>Can the Health Benefits of a Walking-based Exercise Programme be Enhanced by Co-ingestion of a Lipid-lowering Drug?</brief_title>
  <official_title>Can the Health Benefits of a Walking-based Exercise Programme be Enhanced by Co-ingestion of a Lipid-lowering Drug?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Liverpool John Moores University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Diabetes UK</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Liverpool University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Royal Liverpool University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Liverpool John Moores University</source>
  <oversight_info>
    <has_dmc>No</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>
      Study investigates the hypothesis that an exercise programme of steady walking will have&#xD;
      larger effects on insulin sensitivity and glycemic control when combined with Acipimox intake&#xD;
      prior to each exercise session in people with pre-diabetes. Thirty-four sedentary,&#xD;
      overweight/obese people (aged 25-50 years, BMI &gt;28 kg.m-2) with pre-diabetes will be&#xD;
      recruited using the same strategy as study 2 and split into two groups (detailed below).&#xD;
      Participants will undergo several pre- intervention assessments, followed by a 12-week&#xD;
      walking based intervention combined with either Acipimox ingestion or no drug ingestion, pre-&#xD;
      each exercise session. Following this, the post-assessment measures will identical to the&#xD;
      pre-assessment measures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study 3 investigates the hypothesis that an exercise programme of steady walking will have&#xD;
      larger effects on insulin sensitivity and glycaemic control when combined with Acipimox&#xD;
      intake prior to each exercise session in people with prediabetes. Thirty-four sedentary,&#xD;
      overweight/obese people (aged 25-50 years, BMI &gt;28 kg.m-2) with prediabetes will be recruited&#xD;
      using the same strategy as study 2 and split into two groups (detailed below).&#xD;
&#xD;
      Pre-intervention assessments:&#xD;
&#xD;
      Visit 1: Participants will undergo an assessment of body composition (DXA) and undertake a&#xD;
      graded treadmill walking test to estimate maximal aerobic fitness (VO2max).&#xD;
&#xD;
      Visit 2: Participants will be able to opt to undergo an MRI scan, taking place before&#xD;
      breakfast. The MRI scan is used to measure fat stored in the liver and muscles. A continuous&#xD;
      glucose monitoring (CGM) sensor will be inserted to measure insulin sensitivity.&#xD;
&#xD;
      Visit 3: Participants will arrive at the laboratory after an overnight fast (&gt;10 h) to&#xD;
      undergo a Hyperinsulinaemic euglycaemic clamp to assess whole-body insulin sensitivity.&#xD;
      Plasma glucose will be measured at regular intervals and muscle biopsies will be obtained&#xD;
      from the vastus lateralis muscle of one leg before and after 2 hours of the clamp.&#xD;
&#xD;
      Exercise intervention: Pairs of participants from each group (matched for gender, age and&#xD;
      VO2max) will be randomized to undertake 12 weeks of steady walking combined with ingestion of&#xD;
      either Acipimox or placebo in a counter-balanced, double-blind design. Supervised treadmill&#xD;
      walking sessions will be undertaken at LJMU three times per week, with exercise performed at&#xD;
      a speed equivalent to 45% VO2max. Participants will initially exercise for 30 mins per&#xD;
      session (weeks 1 and 2), and each session will increase in duration by 5 mins every 2 weeks&#xD;
      thereafter, up to 50 minutes of exercise. 1 hour before each walking session, participants&#xD;
      will ingest either 250 mg Acipimox or nothing.&#xD;
&#xD;
      Post-intervention assessments: The post-intervention assessments will be identical in all&#xD;
      respects to the pre-intervention assessments and will be commenced ≥72 hours after the final&#xD;
      training session.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    COVID-19&#xD;
  </why_stopped>
  <start_date type="Actual">January 6, 2020</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">December 2022</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>34 pre-diabetics will be split into 2 groups; one will ingest Acipimox for 12-weeks and the other will ingest nothing.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>both participants and investigators will know if they are ingesting Acipimox or nothing.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin Sensitivity</measure>
    <time_frame>A change in insulin sensitivity from baseline will be compared to week 12.</time_frame>
    <description>A pre- and post- hyperinsulinaemic euglycaemic clamp will assess changes in whole body insulin sensitivity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sub-maximal VO2 walking test</measure>
    <time_frame>A change in aerobic capacity (VO2) from baseline will be compared to week 12.</time_frame>
    <description>Participants will be assessed for pre- and post- maximal aerobic capacity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Liver Fat</measure>
    <time_frame>The change percentage of liver fat will be measured at baseline and be compared to value at the end of week 12.</time_frame>
    <description>A pre- and post- intervention MRI scan will show any changes in Liver Fat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Intramuscular GLUT4</measure>
    <time_frame>A change in the co-localisation of GLUT4 will be assessed from the values from the clamp at baseline, to the clamp at week 12 after the intervention.</time_frame>
    <description>Muscle biopsy samples will undergo analysis of mechanisms for insulin sensitivity and lipid metabolites using confocal immunofluorescence microscopy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in intramuscular DAGs</measure>
    <time_frame>A change in the amount of DAGs will be assessed from the values from the clamp at baseline, to the clamp at week 12 after the intervention.</time_frame>
    <description>The amount of DAGs within the muscle will be analysed using liquid chromatography-mass spectrometry.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">34</enrollment>
  <condition>Pre-diabetes</condition>
  <arm_group>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Individuals in this group will undergo pre-assessments for body composition (DXA), Insulin sensitivity (Hyperinsulinaemic Euglycaemic clamp and continuous glucose monitor), muscle biopsies pre- and post- clamp for analysis of lipid metabolites, liver fat (MRI) and exercise capacity (VO2 max). Participants will then ingest 250 mg of Acipimox 1 hour before each exercise session of the 12 week intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No drug</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Individuals in this group will undergo pre-assessments for body composition (DXA), Insulin sensitivity (Hyperinsulinaemic Euglycaemic clamp and continuous glucose monitor) with muscle biopsies pre- and post- clamp for analysis of lipid metabolites, liver fat (MRI) and exercise capacity (VO2 max). Participants will then ingest nothing prior to their exercise sessions during the 12-week exercise programme.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exercise Program</intervention_name>
    <description>12-week walking based intervention (3 sessions per week)</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>DXA</intervention_name>
    <description>Participants will undergo an assessment of body composition (DXA)</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>used to measure fat stored in the liver</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Hyperinsulinaemic Euglycaemic Clamp</intervention_name>
    <description>Participants will arrive at the laboratory after an overnight fast (&gt;10 h) to undergo a Hyperinsulinaemic euglycaemic clamp to assess whole-body insulin sensitivity. Plasma glucose will be measured at regular intervals and muscle biopsies will be obtained from the vastus lateralis muscle of one leg before and after 2 hours of the clamp.</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>VO2 Max</intervention_name>
    <description>Assessment of maximum aerobic capacity.</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Continuous Glucose Monitor</intervention_name>
    <description>CGM sensor will be inserted to measure insulin sensitivity over a 24hr period.</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Muscle Biopsies</intervention_name>
    <description>Participants will undergo muscle biopsies pre and post the hyperinsulinemic euglyceamic clamp from the vastus lateralis.</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acipimox 250 MG</intervention_name>
    <description>Participants will be randomised into two groups. One group will be prescribed Acipimox that will be taken 1 hour prior to each exercise session. The other group will take no drug.</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  BMI &gt;28 kg.m-2&#xD;
&#xD;
          -  Pre-diabetic&#xD;
&#xD;
          -  Not currently using any anti-diabetes medication&#xD;
&#xD;
          -  Physically inactive (performing less than two 30 min structured exercise sessions per&#xD;
             week for the last year)&#xD;
&#xD;
          -  Not pregnant or currently breast feeding&#xD;
&#xD;
          -  Pre-menopausal&#xD;
&#xD;
          -  Not currently involved in a weight loss programme or using weight loss medication&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Involved in regular exercise (engaged in more than 2 sessions of structured exercise&#xD;
             of &gt;30 min per week)&#xD;
&#xD;
          -  Currently using anti-diabetes medication (e.g. insulin, metformin)&#xD;
&#xD;
          -  Currently using niacin/vitamin B3 supplements&#xD;
&#xD;
          -  Pregnant or breast feeding&#xD;
&#xD;
          -  Currently engaged in active weight loss programme or using weight loss medication&#xD;
&#xD;
          -  Diagnosed with chronic kidney disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jennifer s Barrett, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Liverpool John Moores University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Liverpool John Moores University</name>
      <address>
        <city>Liverpool</city>
        <state>Merseyside</state>
        <zip>L18 8EU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 17, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 18, 2019</study_first_posted>
  <last_update_submitted>September 7, 2021</last_update_submitted>
  <last_update_submitted_qc>September 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Liverpool John Moores University</investigator_affiliation>
    <investigator_full_name>Jennifer Barrett</investigator_full_name>
    <investigator_title>PhD researcher in Exercise Metabolism</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prediabetic State</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acipimox</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/NCT03809793
org study id: 250408
nct id: NCT03809793
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Study investigates the hypothesis that an exercise programme of steady walking will have
      larger effects on insulin sensitivity and glycemic control when combined with Acipimox intake
      prior to each exercise session in people with pre-diabetes. Thirty-four sedentary,
      overweight/obese people (aged 25-50 years, BMI >28 kg.m-2) with pre-diabetes will be
      recruited using the same strategy as study 2 and split into two groups (detailed below).
      Participants will undergo several pre- intervention assessments, followed by a 12-week
      walking based intervention combined with either Acipimox ingestion or no drug ingestion, pre-
      each exercise session. Following this, the post-assessment measures will identical to the
      pre-assessment measures.
Study 3 investigates the hypothesis that an exercise programme of steady walking will have
      larger effects on insulin sensitivity and glycaemic control when combined with Acipimox
      intake prior to each exercise session in people with prediabetes. Thirty-four sedentary,
      overweight/obese people (aged 25-50 years, BMI >28 kg.m-2) with prediabetes will be recruited
      using the same strategy as study 2 and split into two groups (detailed below).

      Pre-intervention assessments:

      Visit 1: Participants will undergo an assessment of body composition (DXA) and undertake a
      graded treadmill walking test to estimate maximal aerobic fitness (VO2max).

      Visit 2: Participants will be able to opt to undergo an MRI scan, taking place before
      breakfast. The MRI scan is used to measure fat stored in the liver and muscles. A continuous
      glucose monitoring (CGM) sensor will be inserted to measure insulin sensitivity.

      Visit 3: Participants will arrive at the laboratory after an overnight fast (>10 h) to
      undergo a Hyperinsulinaemic euglycaemic clamp to assess whole-body insulin sensitivity.
      Plasma glucose will be measured at regular intervals and muscle biopsies will be obtained
      from the vastus lateralis muscle of one leg before and after 2 hours of the clamp.

      Exercise intervention: Pairs of participants from each group (matched for gender, age and
      VO2max) will be randomized to undertake 12 weeks of steady walking combined with ingestion of
      either Acipimox or placebo in a counter-balanced, double-blind design. Supervised treadmill
      walking sessions will be undertaken at LJMU three times per week, with exercise performed at
      a speed equivalent to 45% VO2max. Participants will initially exercise for 30 mins per
      session (weeks 1 and 2), and each session will increase in duration by 5 mins every 2 weeks
      thereafter, up to 50 minutes of exercise. 1 hour before each walking session, participants
      will ingest either 250 mg Acipimox or nothing.

      Post-intervention assessments: The post-intervention assessments will be identical in all
      respects to the pre-intervention assessments and will be commenced ≥72 hours after the final
      training session.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 34 pre-diabetics will be split into 2 groups; one will ingest Acipimox for 12-weeks and the other will ingest nothing.
primary purpose: Prevention
masking: None (Open Label)
masking description: both participants and investigators will know if they are ingesting Acipimox or nothing.
measure: Insulin Sensitivity
time frame: A change in insulin sensitivity from baseline will be compared to week 12.
description: A pre- and post- hyperinsulinaemic euglycaemic clamp will assess changes in whole body insulin sensitivity.
measure: Sub-maximal VO2 walking test
time frame: A change in aerobic capacity (VO2) from baseline will be compared to week 12.
description: Participants will be assessed for pre- and post- maximal aerobic capacity.
measure: Percentage of Liver Fat
time frame: The change percentage of liver fat will be measured at baseline and be compared to value at the end of week 12.
description: A pre- and post- intervention MRI scan will show any changes in Liver Fat
measure: Changes in Intramuscular GLUT4
time frame: A change in the co-localisation of GLUT4 will be assessed from the values from the clamp at baseline, to the clamp at week 12 after the intervention.
description: Muscle biopsy samples will undergo analysis of mechanisms for insulin sensitivity and lipid metabolites using confocal immunofluorescence microscopy.
measure: Change in intramuscular DAGs
time frame: A change in the amount of DAGs will be assessed from the values from the clamp at baseline, to the clamp at week 12 after the intervention.
description: The amount of DAGs within the muscle will be analysed using liquid chromatography-mass spectrometry.
arm group label: Acipimox ingestion
arm group type: Active Comparator
description: Individuals in this group will undergo pre-assessments for body composition (DXA), Insulin sensitivity (Hyperinsulinaemic Euglycaemic clamp and continuous glucose monitor), muscle biopsies pre- and post- clamp for analysis of lipid metabolites, liver fat (MRI) and exercise capacity (VO2 max). Participants will then ingest 250 mg of Acipimox 1 hour before each exercise session of the 12 week intervention.
arm group label: No drug
arm group type: Placebo Comparator
description: Individuals in this group will undergo pre-assessments for body composition (DXA), Insulin sensitivity (Hyperinsulinaemic Euglycaemic clamp and continuous glucose monitor) with muscle biopsies pre- and post- clamp for analysis of lipid metabolites, liver fat (MRI) and exercise capacity (VO2 max). Participants will then ingest nothing prior to their exercise sessions during the 12-week exercise programme.
intervention type: Other
intervention name: Exercise Program
description: 12-week walking based intervention (3 sessions per week)
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Diagnostic Test
intervention name: DXA
description: Participants will undergo an assessment of body composition (DXA)
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Diagnostic Test
intervention name: MRI
description: used to measure fat stored in the liver
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Diagnostic Test
intervention name: Hyperinsulinaemic Euglycaemic Clamp
description: Participants will arrive at the laboratory after an overnight fast (>10 h) to undergo a Hyperinsulinaemic euglycaemic clamp to assess whole-body insulin sensitivity. Plasma glucose will be measured at regular intervals and muscle biopsies will be obtained from the vastus lateralis muscle of one leg before and after 2 hours of the clamp.
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Diagnostic Test
intervention name: VO2 Max
description: Assessment of maximum aerobic capacity.
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Diagnostic Test
intervention name: Continuous Glucose Monitor
description: CGM sensor will be inserted to measure insulin sensitivity over a 24hr period.
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Procedure
intervention name: Muscle Biopsies
description: Participants will undergo muscle biopsies pre and post the hyperinsulinemic euglyceamic clamp from the vastus lateralis.
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Drug
intervention name: Acipimox 250 MG
description: Participants will be randomised into two groups. One group will be prescribed Acipimox that will be taken 1 hour prior to each exercise session. The other group will take no drug.
arm group label: Acipimox ingestion
criteria: 
gender: All
minimum age: 25 Years
maximum age: 50 Years
healthy volunteers: No
last name: Jennifer s Barrett, PhD
role: Principal Investigator
affiliation: Liverpool John Moores University
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Liverpool John Moores University
investigator full name: Jennifer Barrett
investigator title: PhD researcher in Exercise Metabolism
mesh term: Prediabetic State
mesh term: Acipimox
sharing ipd: No