<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/NCT03041363</url>
  </required_header>
  <id_info>
    <org_study_id>STU 062016-105</org_study_id>
    <secondary_id>R01NS094257</secondary_id>
    <nct_id>NCT03041363</nct_id>
  </id_info>
  <brief_title>Treatment Development of Triheptanoin (G1D)</brief_title>
  <official_title>Treatment Development of Triheptanoin (C7) for Glucose Transporter Type I Deficiency (G1D): A Phase I Maximum Tolerable Dose Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Juan Pascual</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To determine the maximum tolerated dose (MTD), as a percentage of calories consumed, of&#xD;
      triheptanoin (C7 oil; C7) in a pediatric and adult patient population genetically diagnosed&#xD;
      with glucose transporter type 1 deficiency disorder (G1D).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial will use an open-label, standard 3+3 phase I design for determining the MTD of&#xD;
      orally-administered C7 in G1D.&#xD;
&#xD;
      Triheptanoin: a triglyceride oil containing three odd-carbon chain-length fatty acids (i.e.,&#xD;
      a triglyceride of 7-carbon heptanoic acid). Triheptanoin will be taken 4 times per day&#xD;
      (approximately every 6 hours) by mouth. it is dosed 4 times per day, divided evenly, and the&#xD;
      total C7 daily dose will re-place 40% or 45% (depending on group) of the daily caloric intake&#xD;
      from fat in the usual diet, based on current protocol guidelines. The oil should be taken&#xD;
      approximately one hour before meals, and will be mixed with fat-free, sugar-free yogurt or&#xD;
      pudding for administration.&#xD;
&#xD;
      Up to thirty-six subjects will be enrolled in a 10-day maximum tolerable dose trial of C7.&#xD;
      Initiation of C7 dosing will be conducted in the Children's Medical Center Dallas ambulatory&#xD;
      Care Pavilion neurology Clinic. Subjects will be provided with C7 oil to take over the 7 days&#xD;
      of administration.&#xD;
&#xD;
      Subjects will not be required to stop other medications. Subjects will be directed to&#xD;
      maintain their usual medications, including rescue seizure medications, as necessary for the&#xD;
      course of the study. Subjects may have any clinical medical records transferred back to their&#xD;
      referring physician at completion of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 29, 2017</start_date>
  <completion_date type="Actual">December 22, 2017</completion_date>
  <primary_completion_date type="Actual">December 22, 2017</primary_completion_date>
  <phase>Phase 1</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>
    <intervention_model_description>The trial will use an open-label, standard 3+3 phase 1 design for determining the MTD of orally administered C7 in G1D.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose trial</measure>
    <time_frame>medication taken daily for 7 days.</time_frame>
    <description>To determine the MTD as a percentage of calories consumed in pediatric and adult patient population.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Epilepsy</condition>
  <condition>GLUT1DS1</condition>
  <condition>Glut1 Deficiency Syndrome 1, Autosomal Recessive</condition>
  <condition>Glucose Metabolism Disorders</condition>
  <condition>Glucose Transport Defect</condition>
  <condition>Glucose Transporter Type 1 Deficiency Syndrome</condition>
  <condition>Glucose Transporter Protein Type 1 Deficiency Syndrome</condition>
  <arm_group>
    <arm_group_label>Triheptanoin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose 1 C7 administered as 40% daily caloric intake. Dose 2. C7 administered as 45% daily caloric intake.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Triheptanoin</intervention_name>
    <description>Triheptanoin will be administered for 7 days 4 times daily.</description>
    <arm_group_label>Triheptanoin</arm_group_label>
    <other_name>C7</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of glucose transporter type I deficiency (G1D) confirmed by genotyping or&#xD;
             PET scan of the brain.&#xD;
&#xD;
          -  Stable on no dietary therapy other than Modified Atkins diet (i.e., on no dietary&#xD;
             therapy for 1 month, including, but not limited to, medium chain triglyceride&#xD;
             therapy).&#xD;
&#xD;
          -  Males and females 2 years 6 months to 35 years 11 months old, inclusive.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of life-threatening seizure episodes, including but not&#xD;
             limited to status epilepticus and cardiac arrest.&#xD;
&#xD;
          -  Subjects with evidence of independent, unrelated metabolic and/or genetic disease.&#xD;
&#xD;
          -  Subjects with a body mass index (BMI) greater than or equal to 30.&#xD;
&#xD;
          -  Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome,&#xD;
             Crohn's disease, or colitis, which could increase the subject's risk of developing&#xD;
             diarrhea or stomach pain.&#xD;
&#xD;
          -  Subjects currently on dietary therapy (i.e., ketogenic diet, medium chain&#xD;
             triglyceride-supplemented diets, Atkins diet, low glycemic index diet, and related&#xD;
             diets).&#xD;
&#xD;
          -  Women who are pregnant or breast-feeding may not participate.&#xD;
&#xD;
          -  Women who plan to become pregnant during the course of the study, or who are unwilling&#xD;
             to use birth control to prevent pregnancy (including abstinence) may not participate.&#xD;
&#xD;
          -  Females age 10 and over will be asked to provide a urine sample for a pregnancy test&#xD;
             via dipstick.&#xD;
&#xD;
          -  Subjects will be asked to agree to abstinence or another form of birth control for the&#xD;
             duration of the study.&#xD;
&#xD;
          -  Allergy/sensitivity to C7.&#xD;
&#xD;
          -  Previous treatment with C7 one month prior to enrollment.&#xD;
&#xD;
          -  Treatment with medium chain triglycerides in the last 30 days.&#xD;
&#xD;
          -  Subjects exhibiting signs of dementia, or diagnosed with any degenerative brain&#xD;
             disorder (such as Alzheimer's disease) that would confound assessment of cognitive&#xD;
             changes, in the opinion of the investigator.&#xD;
&#xD;
          -  Active drug or alcohol use or dependence that, in the opinion of the investigator,&#xD;
             would interfere with adherence to study requirements.&#xD;
&#xD;
          -  Inability or unwillingness of 1 parent or legal guardian/representative to give&#xD;
             written informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>2 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Juan Pascual</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Pascual JM, Liu P, Mao D, Kelly DI, Hernandez A, Sheng M, Good LB, Ma Q, Marin-Valencia I, Zhang X, Park JY, Hynan LS, Stavinoha P, Roe CR, Lu H. Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. JAMA Neurol. 2014 Oct;71(10):1255-65. doi: 10.1001/jamaneurol.2014.1584.</citation>
    <PMID>25110966</PMID>
  </reference>
  <reference>
    <citation>Marin-Valencia I, Good LB, Ma Q, Malloy CR, Pascual JM. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain. J Cereb Blood Flow Metab. 2013 Feb;33(2):175-82. doi: 10.1038/jcbfm.2012.151. Epub 2012 Oct 17.</citation>
    <PMID>23072752</PMID>
  </reference>
  <reference>
    <citation>Pascual JM, Ronen GM. Glucose Transporter Type I Deficiency (G1D) at 25 (1990-2015): Presumptions, Facts, and the Lives of Persons With This Rare Disease. Pediatr Neurol. 2015 Nov;53(5):379-93. doi: 10.1016/j.pediatrneurol.2015.08.001. Epub 2015 Aug 10.</citation>
    <PMID>26341673</PMID>
  </reference>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <last_update_submitted>December 20, 2022</last_update_submitted>
  <last_update_submitted_qc>December 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Juan Pascual</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>Metabolic Diseases</mesh_term>
    <mesh_term>Glucose Metabolism Disorders</mesh_term>
    <mesh_term>Syndrome</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/NCT03041363
org study id: STU 062016-105
secondary id: R01NS094257
nct id: NCT03041363
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To determine the maximum tolerated dose (MTD), as a percentage of calories consumed, of
      triheptanoin (C7 oil; C7) in a pediatric and adult patient population genetically diagnosed
      with glucose transporter type 1 deficiency disorder (G1D).
The trial will use an open-label, standard 3+3 phase I design for determining the MTD of
      orally-administered C7 in G1D.

      Triheptanoin: a triglyceride oil containing three odd-carbon chain-length fatty acids (i.e.,
      a triglyceride of 7-carbon heptanoic acid). Triheptanoin will be taken 4 times per day
      (approximately every 6 hours) by mouth. it is dosed 4 times per day, divided evenly, and the
      total C7 daily dose will re-place 40% or 45% (depending on group) of the daily caloric intake
      from fat in the usual diet, based on current protocol guidelines. The oil should be taken
      approximately one hour before meals, and will be mixed with fat-free, sugar-free yogurt or
      pudding for administration.

      Up to thirty-six subjects will be enrolled in a 10-day maximum tolerable dose trial of C7.
      Initiation of C7 dosing will be conducted in the Children's Medical Center Dallas ambulatory
      Care Pavilion neurology Clinic. Subjects will be provided with C7 oil to take over the 7 days
      of administration.

      Subjects will not be required to stop other medications. Subjects will be directed to
      maintain their usual medications, including rescue seizure medications, as necessary for the
      course of the study. Subjects may have any clinical medical records transferred back to their
      referring physician at completion of the study.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: The trial will use an open-label, standard 3+3 phase 1 design for determining the MTD of orally administered C7 in G1D.
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose trial
time frame: medication taken daily for 7 days.
description: To determine the MTD as a percentage of calories consumed in pediatric and adult patient population.
arm group label: Triheptanoin
arm group type: Experimental
description: Dose 1 C7 administered as 40% daily caloric intake. Dose 2. C7 administered as 45% daily caloric intake.
intervention type: Drug
intervention name: Triheptanoin
description: Triheptanoin will be administered for 7 days 4 times daily.
arm group label: Triheptanoin
other name: C7
criteria: 
gender: All
minimum age: 2 Years
maximum age: 35 Years
healthy volunteers: No
last name: Juan Pascual
role: Principal Investigator
affiliation: UT Southwestern Medical Center
facility: 
country: United States
citation: Pascual JM, Liu P, Mao D, Kelly DI, Hernandez A, Sheng M, Good LB, Ma Q, Marin-Valencia I, Zhang X, Park JY, Hynan LS, Stavinoha P, Roe CR, Lu H. Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. JAMA Neurol. 2014 Oct;71(10):1255-65. doi: 10.1001/jamaneurol.2014.1584.
PMID: 25110966
citation: Marin-Valencia I, Good LB, Ma Q, Malloy CR, Pascual JM. Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain. J Cereb Blood Flow Metab. 2013 Feb;33(2):175-82. doi: 10.1038/jcbfm.2012.151. Epub 2012 Oct 17.
PMID: 23072752
citation: Pascual JM, Ronen GM. Glucose Transporter Type I Deficiency (G1D) at 25 (1990-2015): Presumptions, Facts, and the Lives of Persons With This Rare Disease. Pediatr Neurol. 2015 Nov;53(5):379-93. doi: 10.1016/j.pediatrneurol.2015.08.001. Epub 2015 Aug 10.
PMID: 26341673
responsible party type: Sponsor-Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Juan Pascual
investigator title: PROFESSOR
mesh term: Metabolic Diseases
mesh term: Glucose Metabolism Disorders
mesh term: Syndrome
sharing ipd: No