<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/NCT03019510</url>
  </required_header>
  <id_info>
    <org_study_id>1202202 LIFE</org_study_id>
    <nct_id>NCT03019510</nct_id>
  </id_info>
  <brief_title>Lowering Impaired Fasting Glucose Levels With Exercise</brief_title>
  <acronym>LIFE</acronym>
  <official_title>Dawn Phenomena: Lowering Impaired Fasting Glucose Levels With Exercise (LIFE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Missouri-Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Missouri-Columbia</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Morning hyperglycemia plays a role in the future development of insulin resistance and type 2&#xD;
      diabetes (T2D) (8) and is associated with numerous microvascular and cardiovascular&#xD;
      complications and renal disease. These augmented morning glucose levels are due to an&#xD;
      elevated endogenous glucose production (EGP), as a result of a loss of coordination between&#xD;
      glucose levels and insulin secretion, and possibly hyperglucagonemia during the overnight&#xD;
      period. Exercise stimulates glucose uptake and increases insulin sensitivity acutely, and may&#xD;
      be the best lifestyle intervention to minimize the nocturnal rise in glucose levels.&#xD;
      Prescription of the timing of exercise relative to a meal and/or to the overnight period may&#xD;
      be particularly critical for individuals that have impaired fasting glucose (IFG) levels.&#xD;
      Surprisingly little is known about the overnight period when elevated EGP and the synchrony&#xD;
      between glucose and c-peptide/glucagon levels becomes disturbed. This novel study will&#xD;
      provide insight into the hormonal/metabolic milieu of a dinner meal, the evening and&#xD;
      overnight period that occurs in non-obese, OB and OB+IFG individuals; it will also establish&#xD;
      if the timing of exercise can attenuate nocturnal glucose elevations, and if this is&#xD;
      associated with improved hormonal synchrony. This project will compare EGP, β-cell function&#xD;
      and hormonal responses between morning and evening exercise on the postprandial and overnight&#xD;
      period in obese individuals with/without IFG levels. Fifty-four subjects will be studied&#xD;
      during the evening meal (EGP and β-cell function), postprandially and through the overnight&#xD;
      period (1600-0700 h), allowing us to examine some of the potential mechanisms for the&#xD;
      elevation in overnight glucose levels. This is the first study that will examine this issue&#xD;
      from pre-dinner through the night while previous studies have only examined chronically&#xD;
      fasted individuals and this study will lay the groundwork for understanding the pathology of&#xD;
      the predawn phenomena in OB+IFG individuals. These potentially translational findings may&#xD;
      impact the efficiency of physician communication to patients concerning exercise. These&#xD;
      investigators are one of the few groups that study subjects through the overnight period and&#xD;
      have the facilities and capability to do this research.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In individuals with type 2 diabetes (T2D), chronically elevated glucose and insulin levels&#xD;
      result in numerous health complications. Maintaining tight glucose control is difficult for&#xD;
      individuals with T2D, particularly in the postprandial period and in the morning period just&#xD;
      prior to waking. In the postprandial period, the combined effect of insulin resistance and&#xD;
      beta cell dysfunction results in a prolonged elevation in glucose levels, and augmented&#xD;
      insulin levels in an attempt to reduce the circulating glucose levels. In the overnight&#xD;
      period, there is evidence of enhanced endogenous glucose production and of a disruption of&#xD;
      the interaction between glucose levels and insulin secretion. Early work in individuals with&#xD;
      T2D demonstrated that with continued fasting, glucose levels stopped declining in the evening&#xD;
      and subsequently rose throughout the night to reach a morning maximum, and this elevation&#xD;
      persisted till noon. Additionally these authors demonstrated that insulin levels and insulin&#xD;
      secretion rates did not parallel the nocturnal glucose changes in individuals with T2D, while&#xD;
      in the controls the nocturnal glucose and insulin secretion rates coincided. Evidence is also&#xD;
      emerging that hyperglucagonemia may be occurring in the setting of deficient insulin&#xD;
      secretion, and may be playing a role in the elevated postprandial glucose levels and in the&#xD;
      overnight period. These studies provide preliminary evidence that there is disruption in the&#xD;
      fine coordination between glucose levels and glucagon and insulin secretion, and that this is&#xD;
      exacerbated more in the overnight period than during the waking hours. Previous studies&#xD;
      examining the overnight period have been conducted following prolonged fasting (~24-34 h),&#xD;
      however, most people do not fast for extended periods of time prior to going to bed.&#xD;
      Additionally, individuals with T2D often know that meal composition the evening prior can&#xD;
      exacerbate the elevated fasting glucose levels the following morning, thus highlighting the&#xD;
      need to examine the effect of meal composition on overnight glucose control. To date, very&#xD;
      little is known about the pathology of why fasting glucose levels are elevated in many obese&#xD;
      individuals. There appears to be asynchrony between glucose and insulin levels in the&#xD;
      overnight period but very little research has focused on this phenomenon or how meal&#xD;
      composition affects overnight glucose levels. This study will provide evidence of potential&#xD;
      mechanisms for the elevation in overnight glucose levels and the findings will be&#xD;
      translatable for individuals with impaired fasting glucose (IFG) levels to understand the&#xD;
      importance of meal composition in the evening period.&#xD;
&#xD;
      The specific aims of this project are:&#xD;
&#xD;
        1. To examine the hormonal responses (glucagon, c-peptide, insulin, incretins) in response&#xD;
           to a meal in the postprandial period and the synchronization between glucose and&#xD;
           insulin/glucagon during the overnight period in non-obese individuals and obese&#xD;
           individuals with impaired fasting glucose levels (IFG).&#xD;
&#xD;
        2. To determine if the meal composition (standard meal: 55% carbohydrate, 20% protein, 25%&#xD;
           fat vs. high fat/fructose: 40% carbohydrate- 25% fructose, 40% fat, 20% protein) will&#xD;
           alter the hormonal responses (glucagon, insulin, incretin) in the postprandial period,&#xD;
           and if this change in meal composition will impact glucagon levels and glucose/c-peptide&#xD;
           synchrony in the overnight period.&#xD;
&#xD;
      Experimental design: Subjects will participate three times; 1) no exercise, 2) 2 hr post&#xD;
      dinner exercise, and 3) morning exercise (~7am). The order in which subjects undergo each&#xD;
      treatment will be randomized prior to study enrollment. Eligible subjects will initially&#xD;
      undergo baseline testing for assessment of body composition, exercise stress test and blood&#xD;
      screening. All subjects will have impaired fasting glucose levels. All subjects will undergo&#xD;
      3 study days that will start at ~1600 h and continue until 0700 h the following morning. They&#xD;
      will receive a standard meal (55% carbohydrate, 20% protein, 25% fat) at 1800 h and blood&#xD;
      samples will be taken from ~4:30 pm until 7 am.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2016</start_date>
  <completion_date type="Actual">September 30, 2021</completion_date>
  <primary_completion_date type="Actual">September 1, 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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>fasting glucose level</measure>
    <time_frame>avg of every 15 min for 1 hr will be compared between interventions</time_frame>
    <description>the hour prior to study completion will be used for this measurement</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>endogenous glucose production</measure>
    <time_frame>the endogenous glucose production for 4 hr will be compared between intervention</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>insulin concentrations</measure>
    <time_frame>the insulin concentrations 13 hr will be compared between interventions</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>glucagon concentrations</measure>
    <time_frame>the glucagon concentrations for 13 hr will be compared between interventions</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>beta cell function</measure>
    <time_frame>beta cell function determined for 4 hr postprandial</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Type2 Diabetes</condition>
  <arm_group>
    <arm_group_label>no exercise</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be studied from 6 pm to 7 am following 48 hr of no exercise</description>
  </arm_group>
  <arm_group>
    <arm_group_label>morning exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be studied from 6 pm to 7 am. Subjects will have exercised at 7 am on that day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>evening exercise</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will be studied from 6 pm to 7 am. Subjects will exercise at 8 pm following dinner on the study day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>No exercise</intervention_name>
    <description>No exercise will be done on the day of the study night to be tested</description>
    <arm_group_label>evening exercise</arm_group_label>
    <arm_group_label>morning exercise</arm_group_label>
    <arm_group_label>no exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Morning exercise</intervention_name>
    <description>Early morning exercise will be done on the day of the study night to be tested</description>
    <arm_group_label>evening exercise</arm_group_label>
    <arm_group_label>morning exercise</arm_group_label>
    <arm_group_label>no exercise</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Evening exercise</intervention_name>
    <description>Evening exercise will be done on the day of the study night to be tested</description>
    <arm_group_label>evening exercise</arm_group_label>
    <arm_group_label>morning exercise</arm_group_label>
    <arm_group_label>no exercise</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        25-65 yrs of age body mass index (BMI): 30-45 kg/m2 for the obese subjects &lt;24.5 kg/m2 for&#xD;
        the non-obese subjects weight stable during prior 6 months non-smokers OB with impaired&#xD;
        fasting glucose: elevated elevated morning fasting glucose levels &gt;110 mg/dL for 5 of 7&#xD;
        days non-obese and OB subjects: fasting glucose levels &lt; 100 mg/dL - 2hr OGTT glucose value&#xD;
        &lt;140 mg/dL&#xD;
&#xD;
        Exclusion criteria overt cardiovascular disease sleep apnea surgical history for weight&#xD;
        loss use of weight-loss medications or active dieting participate in exercise &gt; 3 days/wk&#xD;
        per week at a moderate or vigorous intensity pregnant or lactating women. Medications for&#xD;
        glycemic control (including insulin), β-blockers, glucocorticoids, testosterone, or other&#xD;
        medications for chronic pulmonary, cardiac or other systemic diseases.&#xD;
&#xD;
        Significant hypertension BP &gt; 180 systolic or &gt; 100 diastolic, at rest. Untreated&#xD;
        hypothyroidism or hyperthyroidism (will be included if treated and euthyroid) Active users&#xD;
        of tobacco and chronic alcohol abuse. Renal, hepatic, pulmonary, adrenal, or pituitary&#xD;
        disease. Liver function tests with &gt; 2xULN.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jill Kanaley, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Missouri-Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Missouri</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>January 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <last_update_submitted>October 13, 2021</last_update_submitted>
  <last_update_submitted_qc>October 13, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Missouri-Columbia</investigator_affiliation>
    <investigator_full_name>Jill Kanaley</investigator_full_name>
    <investigator_title>professor</investigator_title>
  </responsible_party>
  <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/NCT03019510
org study id: 1202202 LIFE
nct id: NCT03019510
lead sponsor: 
has dmc: No
Morning hyperglycemia plays a role in the future development of insulin resistance and type 2
      diabetes (T2D) (8) and is associated with numerous microvascular and cardiovascular
      complications and renal disease. These augmented morning glucose levels are due to an
      elevated endogenous glucose production (EGP), as a result of a loss of coordination between
      glucose levels and insulin secretion, and possibly hyperglucagonemia during the overnight
      period. Exercise stimulates glucose uptake and increases insulin sensitivity acutely, and may
      be the best lifestyle intervention to minimize the nocturnal rise in glucose levels.
      Prescription of the timing of exercise relative to a meal and/or to the overnight period may
      be particularly critical for individuals that have impaired fasting glucose (IFG) levels.
      Surprisingly little is known about the overnight period when elevated EGP and the synchrony
      between glucose and c-peptide/glucagon levels becomes disturbed. This novel study will
      provide insight into the hormonal/metabolic milieu of a dinner meal, the evening and
      overnight period that occurs in non-obese, OB and OB+IFG individuals; it will also establish
      if the timing of exercise can attenuate nocturnal glucose elevations, and if this is
      associated with improved hormonal synchrony. This project will compare EGP, β-cell function
      and hormonal responses between morning and evening exercise on the postprandial and overnight
      period in obese individuals with/without IFG levels. Fifty-four subjects will be studied
      during the evening meal (EGP and β-cell function), postprandially and through the overnight
      period (1600-0700 h), allowing us to examine some of the potential mechanisms for the
      elevation in overnight glucose levels. This is the first study that will examine this issue
      from pre-dinner through the night while previous studies have only examined chronically
      fasted individuals and this study will lay the groundwork for understanding the pathology of
      the predawn phenomena in OB+IFG individuals. These potentially translational findings may
      impact the efficiency of physician communication to patients concerning exercise. These
      investigators are one of the few groups that study subjects through the overnight period and
      have the facilities and capability to do this research.
In individuals with type 2 diabetes (T2D), chronically elevated glucose and insulin levels
      result in numerous health complications. Maintaining tight glucose control is difficult for
      individuals with T2D, particularly in the postprandial period and in the morning period just
      prior to waking. In the postprandial period, the combined effect of insulin resistance and
      beta cell dysfunction results in a prolonged elevation in glucose levels, and augmented
      insulin levels in an attempt to reduce the circulating glucose levels. In the overnight
      period, there is evidence of enhanced endogenous glucose production and of a disruption of
      the interaction between glucose levels and insulin secretion. Early work in individuals with
      T2D demonstrated that with continued fasting, glucose levels stopped declining in the evening
      and subsequently rose throughout the night to reach a morning maximum, and this elevation
      persisted till noon. Additionally these authors demonstrated that insulin levels and insulin
      secretion rates did not parallel the nocturnal glucose changes in individuals with T2D, while
      in the controls the nocturnal glucose and insulin secretion rates coincided. Evidence is also
      emerging that hyperglucagonemia may be occurring in the setting of deficient insulin
      secretion, and may be playing a role in the elevated postprandial glucose levels and in the
      overnight period. These studies provide preliminary evidence that there is disruption in the
      fine coordination between glucose levels and glucagon and insulin secretion, and that this is
      exacerbated more in the overnight period than during the waking hours. Previous studies
      examining the overnight period have been conducted following prolonged fasting (~24-34 h),
      however, most people do not fast for extended periods of time prior to going to bed.
      Additionally, individuals with T2D often know that meal composition the evening prior can
      exacerbate the elevated fasting glucose levels the following morning, thus highlighting the
      need to examine the effect of meal composition on overnight glucose control. To date, very
      little is known about the pathology of why fasting glucose levels are elevated in many obese
      individuals. There appears to be asynchrony between glucose and insulin levels in the
      overnight period but very little research has focused on this phenomenon or how meal
      composition affects overnight glucose levels. This study will provide evidence of potential
      mechanisms for the elevation in overnight glucose levels and the findings will be
      translatable for individuals with impaired fasting glucose (IFG) levels to understand the
      importance of meal composition in the evening period.

      The specific aims of this project are:

        1. To examine the hormonal responses (glucagon, c-peptide, insulin, incretins) in response
           to a meal in the postprandial period and the synchronization between glucose and
           insulin/glucagon during the overnight period in non-obese individuals and obese
           individuals with impaired fasting glucose levels (IFG).

        2. To determine if the meal composition (standard meal: 55% carbohydrate, 20% protein, 25%
           fat vs. high fat/fructose: 40% carbohydrate- 25% fructose, 40% fat, 20% protein) will
           alter the hormonal responses (glucagon, insulin, incretin) in the postprandial period,
           and if this change in meal composition will impact glucagon levels and glucose/c-peptide
           synchrony in the overnight period.

      Experimental design: Subjects will participate three times; 1) no exercise, 2) 2 hr post
      dinner exercise, and 3) morning exercise (~7am). The order in which subjects undergo each
      treatment will be randomized prior to study enrollment. Eligible subjects will initially
      undergo baseline testing for assessment of body composition, exercise stress test and blood
      screening. All subjects will have impaired fasting glucose levels. All subjects will undergo
      3 study days that will start at ~1600 h and continue until 0700 h the following morning. They
      will receive a standard meal (55% carbohydrate, 20% protein, 25% fat) at 1800 h and blood
      samples will be taken from ~4:30 pm until 7 am.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: fasting glucose level
time frame: avg of every 15 min for 1 hr will be compared between interventions
description: the hour prior to study completion will be used for this measurement
measure: endogenous glucose production
time frame: the endogenous glucose production for 4 hr will be compared between intervention
measure: insulin concentrations
time frame: the insulin concentrations 13 hr will be compared between interventions
measure: glucagon concentrations
time frame: the glucagon concentrations for 13 hr will be compared between interventions
measure: beta cell function
time frame: beta cell function determined for 4 hr postprandial
arm group label: no exercise
arm group type: Placebo Comparator
description: Subjects will be studied from 6 pm to 7 am following 48 hr of no exercise
arm group label: morning exercise
arm group type: Active Comparator
description: Subjects will be studied from 6 pm to 7 am. Subjects will have exercised at 7 am on that day.
arm group label: evening exercise
arm group type: Active Comparator
description: Subjects will be studied from 6 pm to 7 am. Subjects will exercise at 8 pm following dinner on the study day.
intervention type: Behavioral
intervention name: No exercise
description: No exercise will be done on the day of the study night to be tested
arm group label: evening exercise
arm group label: morning exercise
arm group label: no exercise
intervention type: Behavioral
intervention name: Morning exercise
description: Early morning exercise will be done on the day of the study night to be tested
arm group label: evening exercise
arm group label: morning exercise
arm group label: no exercise
intervention type: Behavioral
intervention name: Evening exercise
description: Evening exercise will be done on the day of the study night to be tested
arm group label: evening exercise
arm group label: morning exercise
arm group label: no exercise
criteria: 
gender: All
minimum age: 25 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jill Kanaley, PhD
role: Principal Investigator
affiliation: University of Missouri-Columbia
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Missouri-Columbia
investigator full name: Jill Kanaley
investigator title: professor
sharing ipd: No