<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/NCT03804892</url>
  </required_header>
  <id_info>
    <org_study_id>249734</org_study_id>
    <nct_id>NCT03804892</nct_id>
  </id_info>
  <brief_title>Can Brisk Walking Combined With Ingestion of a Lipid-lowering Drug Improve Fat Metabolism in Muscle?</brief_title>
  <official_title>Can Brisk Walking Combined With Ingestion of a Lipid-lowering Drug Improve Fat Metabolism in Muscle?</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>
      Briefly, participants will be assessed for their eligibility for the study using an oral&#xD;
      glucose tolerance test, which involves drinking a sugary drink followed by a series of small&#xD;
      blood samples. If eligible, participants will be asked to take part in a fitness test and&#xD;
      then two trials which will involve walking on a treadmill at a steady pace. Before and after&#xD;
      the exercise a small piece of muscle will be taken from their thigh under local anaesthesia,&#xD;
      as well as several small blood samples. Muscle muscle samples will be assessed for lipid&#xD;
      metabolites.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The accumulation of fat in skeletal muscle is linked with insulin resistance in obesity and&#xD;
      T2D. However, fat also accumulates in the muscle of lean, healthy people, but they remain&#xD;
      insulin sensitive. This is because healthy people are able to burn this fat to generate&#xD;
      energy during exercise. However, overweight/obese inactive people can't use muscle fat during&#xD;
      exercise in the same manner, which is related to the high blood lipid concentrations that are&#xD;
      observed in these individuals. Acipimox is a lipid-lowering agent that specifically reduces&#xD;
      the breakdown of fat in adipose tissue and has been shown improve the blood lipid profile of&#xD;
      obese individuals and T2D patients, at least in the short-term (1-2 weeks). Previous research&#xD;
      has shown that the combination of Acipimox with exercise restores the ability of obese people&#xD;
      to burn fat during moderate-intensity cycling exercise. It is now important to test whether&#xD;
      Acipimox also increases the ability to burn muscle fat during low-intensity walking in people&#xD;
      with prediabetes. If it does, then the next step will be to test whether the combination of&#xD;
      Acipimox and walking can lead to improved insulin sensitivity and reduced T2D risk over a&#xD;
      longer intervention programme. Twelve people with pre-diabetes will be recruited to undertake&#xD;
      two experimental trials in a randomised order. Each trial will involve walking for 45 minutes&#xD;
      on a treadmill, with muscle biopsies obtained from the thigh before (basal), immediately&#xD;
      following (post-exercise) and 3 h post-exercise. Each trial will be identical, except that&#xD;
      participants will ingest either Acipimox or a placebo in a double-blind design. Muscle&#xD;
      biopsies will be used to examine differences in muscle fat between the two trials.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 1, 2019</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">November 2021</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>Crossover Assignment</intervention_model>
    <intervention_model_description>This study involves 2 trials. Each trial will involve walking for 45 minutes on a treadmill, with muscle biopsies obtained from the thigh before (basal), immediately following (post-exercise) and 3 h post-exercise. Each trial will be identical, except that participants will ingest either Acipimox or a placebo in a double-blind design. Muscle biopsies will be used to examine differences in muscle fat between the two trials</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma fatty acids levels</measure>
    <time_frame>A change in the amount of fatty acids in the blood from baseline, to every 15 minute interval from the ingestion of acipimox up until 2 hours 45 minutes. From this point, samples will be every 30 minutes until 3 hours 45 minutes terminates the trial.</time_frame>
    <description>Blood samples will be assessed for the amount of fatty acids in the blood.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Skeletal muscle Diacylglycerol (DAG) levels</measure>
    <time_frame>A change from baseline DAGs to DAGS immediately post and 3 hours post exercise trial.</time_frame>
    <description>Muscle biopsies will be assessed for lipid metabolites using liquid chromatography-mass spectrometry.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma Glycerol levels</measure>
    <time_frame>A change in the amount of fatty acids in the blood from baseline, to every 15 minute interval from the ingestion of acipimox up until 2 hours 45 minutes. From this point, samples will be every 30 minutes until 3 hours 45 minutes terminates the trial.</time_frame>
    <description>Blood samples will be assessed for the amount of glycerol in the blood throughout the exercise trial.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>IMTG utilisation during exercise</measure>
    <time_frame>A change in amount of IMTG within the muscle from baseline, to immediately post and 3 hours post the exercise intervention.</time_frame>
    <description>Muscle samples will be analysed using confocal immunofluorescence microscopy for the amount of IMTG within the samples.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Pre Diabetes</condition>
  <arm_group>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will undergo pre assessment testing of a body composition (DEXA), a maximal aerobic fitness test, and an oral glucose tolerance test. Following this, participants will ingest 250 mg of Acipimox, before undertaking 45 minutes walking on a treadmill. A muscle biopsy will be taken pre, immediately post and 3 hours post the walking trial. Blood samples will be taken at regular intervals throughout.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No drug</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants will undergo pre assessment testing of a body composition (DEXA), a maximal aerobic fitness test, and an oral glucose tolerance test.Participants will then undergo a 45 minute walk on a treadmill with no Acipimox ingestion. A muscle biopsy will be taken pre, immediately post and 3 hours post the walking trial. Blood samples will be taken at regular intervals throughout.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Body Composition</intervention_name>
    <description>Participants undergo a 5 minute body scan to determine their body composition.</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>Maximal aerobic fitness test</intervention_name>
    <description>Participants will complete a walking fitness text until exhaustion to determine maximal 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>Oral glucose tolerance test</intervention_name>
    <description>Participants will undergo an OGTT to determine insulin sensitivity.</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Muscle biopsy</intervention_name>
    <description>Participants will give a small muscle sample pre-, immediately post and 3 hours post- the exercise trial to be assessed for lipid metabolites.</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Blood samples</intervention_name>
    <description>Participants will give 16 blood samples, to be assessed for fatty acids in the blood.</description>
    <arm_group_label>Acipimox ingestion</arm_group_label>
    <arm_group_label>No drug</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged 25-55 years&#xD;
&#xD;
          -  Overweight or obese (BMI &gt;28 kg.m-2)&#xD;
&#xD;
          -  Have prediabetes&#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 intending to get pregnant during the study) or currently breast&#xD;
             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 programmes 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>55 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, L3 3AF</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jennifer S Barrett, PhD</last_name>
    <phone>07875713844</phone>
    <email>jenni365@hotmail.co.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Sam Shepherd, Dr</last_name>
    <phone>01519046293</phone>
    <email>s.shepherd@ljmu.ac.uk</email>
  </overall_contact_backup>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer S Barrett, PhD</last_name>
      <phone>07875713844</phone>
      <email>j.barrett@2014.ljmu.ac.uk</email>
    </contact>
    <contact_backup>
      <last_name>Sam Shepherd, Dr</last_name>
      <phone>0151231 2121</phone>
      <email>s.shepherd@ljmu.ac.uk</email>
    </contact_backup>
  </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 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 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 8, 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>
  <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/NCT03804892
org study id: 249734
nct id: NCT03804892
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Briefly, participants will be assessed for their eligibility for the study using an oral
      glucose tolerance test, which involves drinking a sugary drink followed by a series of small
      blood samples. If eligible, participants will be asked to take part in a fitness test and
      then two trials which will involve walking on a treadmill at a steady pace. Before and after
      the exercise a small piece of muscle will be taken from their thigh under local anaesthesia,
      as well as several small blood samples. Muscle muscle samples will be assessed for lipid
      metabolites.
The accumulation of fat in skeletal muscle is linked with insulin resistance in obesity and
      T2D. However, fat also accumulates in the muscle of lean, healthy people, but they remain
      insulin sensitive. This is because healthy people are able to burn this fat to generate
      energy during exercise. However, overweight/obese inactive people can't use muscle fat during
      exercise in the same manner, which is related to the high blood lipid concentrations that are
      observed in these individuals. Acipimox is a lipid-lowering agent that specifically reduces
      the breakdown of fat in adipose tissue and has been shown improve the blood lipid profile of
      obese individuals and T2D patients, at least in the short-term (1-2 weeks). Previous research
      has shown that the combination of Acipimox with exercise restores the ability of obese people
      to burn fat during moderate-intensity cycling exercise. It is now important to test whether
      Acipimox also increases the ability to burn muscle fat during low-intensity walking in people
      with prediabetes. If it does, then the next step will be to test whether the combination of
      Acipimox and walking can lead to improved insulin sensitivity and reduced T2D risk over a
      longer intervention programme. Twelve people with pre-diabetes will be recruited to undertake
      two experimental trials in a randomised order. Each trial will involve walking for 45 minutes
      on a treadmill, with muscle biopsies obtained from the thigh before (basal), immediately
      following (post-exercise) and 3 h post-exercise. Each trial will be identical, except that
      participants will ingest either Acipimox or a placebo in a double-blind design. Muscle
      biopsies will be used to examine differences in muscle fat between the two trials.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This study involves 2 trials. Each trial will involve walking for 45 minutes on a treadmill, with muscle biopsies obtained from the thigh before (basal), immediately following (post-exercise) and 3 h post-exercise. Each trial will be identical, except that participants will ingest either Acipimox or a placebo in a double-blind design. Muscle biopsies will be used to examine differences in muscle fat between the two trials
primary purpose: Prevention
masking: None (Open Label)
measure: Plasma fatty acids levels
time frame: A change in the amount of fatty acids in the blood from baseline, to every 15 minute interval from the ingestion of acipimox up until 2 hours 45 minutes. From this point, samples will be every 30 minutes until 3 hours 45 minutes terminates the trial.
description: Blood samples will be assessed for the amount of fatty acids in the blood.
measure: Skeletal muscle Diacylglycerol (DAG) levels
time frame: A change from baseline DAGs to DAGS immediately post and 3 hours post exercise trial.
description: Muscle biopsies will be assessed for lipid metabolites using liquid chromatography-mass spectrometry.
measure: Plasma Glycerol levels
time frame: A change in the amount of fatty acids in the blood from baseline, to every 15 minute interval from the ingestion of acipimox up until 2 hours 45 minutes. From this point, samples will be every 30 minutes until 3 hours 45 minutes terminates the trial.
description: Blood samples will be assessed for the amount of glycerol in the blood throughout the exercise trial.
measure: IMTG utilisation during exercise
time frame: A change in amount of IMTG within the muscle from baseline, to immediately post and 3 hours post the exercise intervention.
description: Muscle samples will be analysed using confocal immunofluorescence microscopy for the amount of IMTG within the samples.
arm group label: Acipimox ingestion
arm group type: Experimental
description: Participants will undergo pre assessment testing of a body composition (DEXA), a maximal aerobic fitness test, and an oral glucose tolerance test. Following this, participants will ingest 250 mg of Acipimox, before undertaking 45 minutes walking on a treadmill. A muscle biopsy will be taken pre, immediately post and 3 hours post the walking trial. Blood samples will be taken at regular intervals throughout.
arm group label: No drug
arm group type: Other
description: Participants will undergo pre assessment testing of a body composition (DEXA), a maximal aerobic fitness test, and an oral glucose tolerance test.Participants will then undergo a 45 minute walk on a treadmill with no Acipimox ingestion. A muscle biopsy will be taken pre, immediately post and 3 hours post the walking trial. Blood samples will be taken at regular intervals throughout.
intervention type: Diagnostic Test
intervention name: Body Composition
description: Participants undergo a 5 minute body scan to determine their body composition.
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Diagnostic Test
intervention name: Maximal aerobic fitness test
description: Participants will complete a walking fitness text until exhaustion to determine maximal aerobic capacity.
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Diagnostic Test
intervention name: Oral glucose tolerance test
description: Participants will undergo an OGTT to determine insulin sensitivity.
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Other
intervention name: Muscle biopsy
description: Participants will give a small muscle sample pre-, immediately post and 3 hours post- the exercise trial to be assessed for lipid metabolites.
arm group label: Acipimox ingestion
arm group label: No drug
intervention type: Other
intervention name: Blood samples
description: Participants will give 16 blood samples, to be assessed for fatty acids in the blood.
arm group label: Acipimox ingestion
arm group label: No drug
criteria: 
gender: All
minimum age: 25 Years
maximum age: 55 Years
healthy volunteers: No
last name: Jennifer S Barrett, PhD
role: Principal Investigator
affiliation: Liverpool John Moores University, L3 3AF
last name: Jennifer S Barrett, PhD
phone: 07875713844
email: jenni365@hotmail.co.uk
last name: Sam Shepherd, Dr
phone: 01519046293
email: s.shepherd@ljmu.ac.uk
facility: 
status: Recruiting
contact: 
contact backup: 
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
sharing ipd: No