<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/NCT02979106</url>
  </required_header>
  <id_info>
    <org_study_id>PB_2016-00289 (302/14)</org_study_id>
    <nct_id>NCT02979106</nct_id>
  </id_info>
  <brief_title>Metabolic Consequences of Heterozygous Hereditary Fructose Intolerance</brief_title>
  <official_title>Are Heterozygous Carriers for Hereditary Fructose Intolerance Predisposed to Metabolic Disturbances When Exposed to Fructose?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Lausanne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Lausanne</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background: High fructose intake increases blood lactate, triglyceride and uric acid&#xD;
      concentrations. Uric acid may contribute to insulin resistance and dyslipidemia in the&#xD;
      general population. In patients with hereditary fructose intolerance fructose consumption is&#xD;
      associated with acute hypoglycemia, renal tubular acidosis, and hyperuricemia.&#xD;
&#xD;
      Objective: We investigated whether asymptomatic carriers for hereditary fructose intolerance&#xD;
      (HFI) would have a higher sensitivity to adverse effects of fructose than the general&#xD;
      population.&#xD;
&#xD;
      Design: Eight subjects heterozygous for HFI (hHFI; 4 males, 4 females) and eight controls&#xD;
      received for 7 days a low fructose diet and on the eighth day ingested a test meal calculated&#xD;
      to provide 25% of basal energy requirement containing labeled fructose (13C fructose 0.35&#xD;
      g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg). Total fructose oxidation, total endogenous&#xD;
      glucose production (by 6,6-2H2-glucose dilution), carbohydrate and lipid oxidation, lipids,&#xD;
      uric acid, lactate, creatinine, urea and amino acids were monitored for 6 hours.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">November 2016</completion_date>
  <primary_completion_date type="Actual">January 2016</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Plasma glucose kinetics</measure>
    <time_frame>-120 min before ingestion of a test meal to 360 min after ingestion of a test meal</time_frame>
    <description>Modelling of rate of glucose appearance after administration of a bolus of 6,6-2H2 glucose (bolus, 2 mg/kg and continuous infusion, 0.02 mg/kg/min) will be measured in fasted and fed conditions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Energy expenditure rate</measure>
    <time_frame>120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal</time_frame>
    <description>Energy expenditure is measured by indirect calorimetry in fasted and fed conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glucose oxidation rate</measure>
    <time_frame>120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal</time_frame>
    <description>glucose oxidation is measured by indirect calorimetry in fasted and fed conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma glucose concentration</measure>
    <time_frame>-120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal</time_frame>
    <description>plasma glucose concentration measured by glucose oxidase</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>plasma insulin concentration</measure>
    <time_frame>-120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal</time_frame>
    <description>Plasma insulin concentration measured by ELISA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fructose oxidation</measure>
    <time_frame>Every 30 min until 360 min after ingestion of a test meal</time_frame>
    <description>Fructose oxidation is measured from 13CO2 production</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Hereditary Fructose Intolerance</condition>
  <condition>Fructose Metabolism, Inborn Errors</condition>
  <condition>Glucose Metabolism Disorders</condition>
  <arm_group>
    <arm_group_label>oral fructose load</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>test meal calculated to provide 25% of basal energy requirement containing 13C-labeled fructose (0.35 g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg).</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Test meal</intervention_name>
    <description>Assessment of postprandial responses to a mixed meal containing fructose in carriers of one mutated ALDOB allele.</description>
    <arm_group_label>oral fructose load</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  8 healthy Volunteers (4 male, 4 female) parents of a child with hereditary fructose&#xD;
             intolerance with ALDOB with heterozygous mutation of ALDOB gene&#xD;
&#xD;
          -  8 healthy Volunteers (4 male, 4 female), healthy with no mutation of ALDOB gene&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Fasting glycemia &gt; 7.0 mmol/L&#xD;
&#xD;
          -  Fasting total triglycerides &gt; 4.0 mmol/L&#xD;
&#xD;
          -  Chronic renal insufficiency (eGFR ≤ 50 ml/min)&#xD;
&#xD;
          -  Anemia (ferritin &lt; 20 ug/L, hemoglobin &lt; 13.5 ou 12.5 g/dl)&#xD;
&#xD;
          -  Drugs&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tappy Luc, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Lausanne</affiliation>
  </overall_official>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>July 15, 2019</last_update_submitted>
  <last_update_submitted_qc>July 15, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Lausanne</investigator_affiliation>
    <investigator_full_name>Luc Tappy, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolism, Inborn Errors</mesh_term>
    <mesh_term>Fructose Intolerance</mesh_term>
    <mesh_term>Fructose Metabolism, Inborn Errors</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Glucose Metabolism Disorders</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/NCT02979106
org study id: PB_2016-00289 (302/14)
nct id: NCT02979106
lead sponsor: 
has dmc: No
Background: High fructose intake increases blood lactate, triglyceride and uric acid
      concentrations. Uric acid may contribute to insulin resistance and dyslipidemia in the
      general population. In patients with hereditary fructose intolerance fructose consumption is
      associated with acute hypoglycemia, renal tubular acidosis, and hyperuricemia.

      Objective: We investigated whether asymptomatic carriers for hereditary fructose intolerance
      (HFI) would have a higher sensitivity to adverse effects of fructose than the general
      population.

      Design: Eight subjects heterozygous for HFI (hHFI; 4 males, 4 females) and eight controls
      received for 7 days a low fructose diet and on the eighth day ingested a test meal calculated
      to provide 25% of basal energy requirement containing labeled fructose (13C fructose 0.35
      g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg). Total fructose oxidation, total endogenous
      glucose production (by 6,6-2H2-glucose dilution), carbohydrate and lipid oxidation, lipids,
      uric acid, lactate, creatinine, urea and amino acids were monitored for 6 hours.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Plasma glucose kinetics
time frame: -120 min before ingestion of a test meal to 360 min after ingestion of a test meal
description: Modelling of rate of glucose appearance after administration of a bolus of 6,6-2H2 glucose (bolus, 2 mg/kg and continuous infusion, 0.02 mg/kg/min) will be measured in fasted and fed conditions
measure: Energy expenditure rate
time frame: 120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
description: Energy expenditure is measured by indirect calorimetry in fasted and fed conditions
measure: Glucose oxidation rate
time frame: 120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
description: glucose oxidation is measured by indirect calorimetry in fasted and fed conditions
measure: Plasma glucose concentration
time frame: -120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
description: plasma glucose concentration measured by glucose oxidase
measure: plasma insulin concentration
time frame: -120 min before ingestion of a test meal, and every 30 min until 360 min after ingestion of a test meal
description: Plasma insulin concentration measured by ELISA
measure: Fructose oxidation
time frame: Every 30 min until 360 min after ingestion of a test meal
description: Fructose oxidation is measured from 13CO2 production
arm group label: oral fructose load
arm group type: Experimental
description: test meal calculated to provide 25% of basal energy requirement containing 13C-labeled fructose (0.35 g/kg), protein (0.21 g/kg) and lipid (0.22 g/kg).
intervention type: Other
intervention name: Test meal
description: Assessment of postprandial responses to a mixed meal containing fructose in carriers of one mutated ALDOB allele.
arm group label: oral fructose load
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Tappy Luc, MD
role: Study Director
affiliation: University of Lausanne
responsible party type: Principal Investigator
investigator affiliation: University of Lausanne
investigator full name: Luc Tappy, MD
investigator title: Professor
mesh term: Metabolism, Inborn Errors
mesh term: Fructose Intolerance
mesh term: Fructose Metabolism, Inborn Errors
mesh term: Metabolic Diseases
mesh term: Glucose Metabolism Disorders
sharing ipd: No