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An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome (GLUT1DS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02036853
Recruitment Status : Completed
First Posted : January 15, 2014
Results First Posted : January 28, 2021
Last Update Posted : January 28, 2021
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Adrian Lacy, Cook Children's Health Care System

Tracking Information
First Submitted Date  ICMJE January 13, 2014
First Posted Date  ICMJE January 15, 2014
Results First Submitted Date  ICMJE January 2, 2020
Results First Posted Date  ICMJE January 28, 2021
Last Update Posted Date January 28, 2021
Study Start Date  ICMJE February 20, 2014
Actual Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 26, 2021)
  • Reported Change in Seizures Frequency From Baseline at 13 Weeks [ Time Frame: Baseline and 13 weeks ]
    A seizure diary was used to track date, type, number, and unusual presentation of seizures. Subjects were given a seizure diary at screening to record daily seizure activity for incremental periods of time. Unless otherwise waived, subjects complete this form daily during the screening period and for two weeks prior to each subsequent study visit.
  • Reported Change in Seizures Frequency From Baseline at 26 Weeks [ Time Frame: Baseline and 26 weeks ]
    A seizure diary was used to track date, type, number, and unusual presentation of seizures. Subjects were given a seizure diary at screening to record daily seizure activity for incremental periods of time. Unless otherwise waived, subjects complete this form daily during the screening period and for two weeks prior to each subsequent study visit. The table below represents the change in seizure frequency from baseline for each time point.
  • Reported Change in Seizures Frequency From Baseline at 1 Year [ Time Frame: Baseline and one yr ]
    A seizure diary was used to track date, type, number, and unusual presentation of seizures. Subjects were given a seizure diary at screening to record daily seizure activity for incremental periods of time. Unless otherwise waived, subjects complete this form daily during the screening period and for two weeks prior to each subsequent study visit. The table below represents the change in seizure frequency from baseline for each time point.
  • Reported Change in Seizures Frequency From Baseline at 18 Months [ Time Frame: Baseline and 18 months ]
    A seizure diary was used to track date, type, number, and unusual presentation of seizures. Subjects were given a seizure diary at screening to record daily seizure activity for incremental periods of time. Unless otherwise waived, subjects complete this form daily during the screening period and for two weeks prior to each subsequent study visit. The table below represents the change in seizure frequency from baseline for each time point.
  • Reported Change in Seizures Frequency From Baseline at 2 Years [ Time Frame: Baseline and two yrs ]
    A seizure diary was used to track date, type, number, and unusual presentation of seizures. Subjects were given a seizure diary at screening to record daily seizure activity for incremental periods of time. Unless otherwise waived, subjects complete this form daily during the screening period and for two weeks prior to each subsequent study visit. The table below represents the change in seizure frequency from baseline for each time point.
  • Reported Change in Seizures Frequency From Baseline at 3 Years [ Time Frame: Baseline and three yrs ]
    A seizure diary was used to track date, type, number, and unusual presentation of seizures. Subjects were given a seizure diary at screening to record daily seizure activity for incremental periods of time. Unless otherwise waived, subjects complete this form daily during the screening period and for two weeks prior to each subsequent study visit. The table below represents the change in seizure frequency from baseline for each time point.
  • Reported Change in Seizure Frequency From Baseline at 4 Years [ Time Frame: Baseline and four yrs ]
    A seizure diary was used to track date, type, number, and unusual presentation of seizures. Subjects were given a seizure diary at screening to record daily seizure activity for incremental periods of time. Unless otherwise waived, subjects complete this form daily during the screening period and for two weeks prior to each subsequent study visit. The table below represents the change in seizure frequency from baseline for each time point.
  • Reported Change in Seizure Frequency From Baseline at 5 Years [ Time Frame: Baseline and five yrs ]
    A seizure diary was used to track date, type, number, and unusual presentation of seizures. Subjects were given a seizure diary at screening to record daily seizure activity for incremental periods of time. Unless otherwise waived, subjects complete this form daily during the screening period and for two weeks prior to each subsequent study visit. The table below represents the change in seizure frequency from baseline for each time point.
Original Primary Outcome Measures  ICMJE
 (submitted: January 13, 2014)
Change in seizure frequency from historical baseline [ Time Frame: 13 weeks, 26 weeks, 1 yr, 18 months, 2 yrs, 3 yrs, 4 yrs ]
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome
Official Title  ICMJE An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome (GLUT1 DS)
Brief Summary

This study is being done to assess the safety and long-term efficacy of triheptanoin in pediatric patients with Glut1 DS over a 5-year treatment period. Glut 1 is a protein that helps transport glucose to the brain. Glucose is the brain's primary source of energy. Glut 1 DS prevents this protein from being effectively produced, causing deprivation of energy to the neurons of the of the brain.

Glut1 DS is a severely debilitating disease characterized by seizures, developmental delay and movement disorder. There are currently no approved treatments specific to Glut1 DS. Treatment generally includes medications for control of seizures. The use of a ketogenic diet can be effective in controlling seizures when medications are ineffective or provide insufficient control. However, the ketogenic diet may be very difficult for patients to maintain for long periods of time, and there may be negative secondary long-term effects of ketogenic diet.. Triheptanoin is metabolized to molecules that can provide an alternative energy source to the brain, and appears to help in controlling seizures without many of the difficulties of the ketogenic diet.

Eligible patients may be those who have been diagnosed with GLUT1 DS, and have discontinued or are not currently on ketogenic diet, or are able to tolerate triheptanoin if they have been treated or are currently being treated with triheptanoin and do not qualify for any other clinical trial.

Detailed Description

Triheptanoin is proposed for the treatment of seizures in glucose transporter type-1 deficiency syndrome (Glut1 DS). Glut1 DS is a rare disease with an estimated US prevalence of ~3,300.

The proposed study is an open-label study to assess the safety and long-term efficacy of triheptanoin in patients with Glut1 DS over a 5-year treatment period. Eligible patients may be those who are able to tolerate triheptanoin if they have been treated or are currently being treated with triheptanoin and do not qualify for any other clinical trial. Subjects previously treated with triheptanoin will continue to dose at approximately 35% of total daily calories (~1-4g/kg/day, depending on age). Subjects who are naïve to triheptanoin will begin a 2-week fixed titration schedule up until they have reached 35% of total daily calories.

The primary objective of the study is to evaluate the safety of triheptanoin via adverse event rates and laboratory values. The secondary objective is to evaluate the long-term efficacy of triheptanoin as measured by the change in seizure frequency from historical baseline.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Glucose Transporter Type-1 Deficiency Syndrome (Glut1 DS)
Intervention  ICMJE Drug: Triheptanoin

Schedule A: Subjects previously treated with triheptanoin will continue to dose at approximately 35% of total daily calories (~1-4g/kg/day, depending on age).

Schedule B: Subjects who are naïve to triheptanoin will begin a 2-week fixed titration schedule up until they have reached 35% of total daily calories (~1-4 g/kg/day depending on age). If a subject has not reached the target of 35% of total daily calories, by the end of the 2-week fixed titration period, dose titration should continue until achieved or until the maximally tolerated dose has been established.

Study Arms  ICMJE
  • Experimental: Schedule A
    Subjects previously treated with triheptanoin
    Intervention: Drug: Triheptanoin
  • Experimental: Schedule B
    Naïve to triheptanoin
    Intervention: Drug: Triheptanoin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 26, 2021)
20
Original Estimated Enrollment  ICMJE
 (submitted: January 13, 2014)
50
Actual Study Completion Date  ICMJE June 30, 2019
Actual Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Individuals eligible to participate in this study must meet all of the following criteria:

  1. Patients with GLUT1 DS by physician diagnosis
  2. Males and females, aged 1 to 50 years
  3. Allowed to be on concomitant AEDs
  4. Patients are able to tolerate triheptanoin if they have been (or are currently being) treated with this medication
  5. Must, in the opinion of the investigator, be willing and able to comply with study procedures and schedule
  6. Provide written assent (if appropriate) and written informed consent by a Legally Authorized Representative (LAR) after the nature of the study has been explained, and prior to any research-related procedures
  7. Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study
  8. Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study

Exclusion Criteria:

Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:

  1. Patients and their Legally Authorized Representatives (as appropriate) not willing or able to give written or verbal assent or written informed consent.
  2. Concomitant administration of a ketogenic diet for the treatment of GLUT1 deficiency
  3. Concomitant administration of valproic acid
  4. In the Investigator's opinion, the patient may not be compliant
  5. Pregnant or breastfeeding an infant at screening
  6. Has a concurrent disease or condition, or laboratory abnormality that, in the view of the Investigator, places the subject at high risk for adverse events, or introduces additional safety concerns
  7. History of or current suicidal ideation, behavior and attempts
  8. Patient qualifies for any other clinical trial designed to progressively evaluate the safety and efficacy of triheptanoin as approved by the FDA under a separate IND which is open at Cook Children's
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02036853
Other Study ID Numbers  ICMJE 2013-NEUR-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Adrian Lacy, Cook Children's Health Care System
Study Sponsor  ICMJE Adrian Lacy
Collaborators  ICMJE Ultragenyx Pharmaceutical Inc
Investigators  ICMJE
Principal Investigator: Adrian Lacy, MD Cook Children's Medical Center
PRS Account Cook Children's Health Care System
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP