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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02036853
Recruitment Status : Recruiting
First Posted : January 15, 2014
Last Update Posted : January 25, 2018
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Adrian Lacy, Cook Children's Health Care System

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.


Condition or disease Intervention/treatment Phase
Glucose Transporter Type-1 Deficiency Syndrome (Glut1 DS) Drug: Triheptanoin Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome (GLUT1 DS)
Study Start Date : January 2014
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Experimental: Schedule A
Subjects previously treated with triheptanoin
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.


Experimental: Schedule B
Naïve to triheptanoin
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.





Primary Outcome Measures :
  1. Change in seizure frequency from historical baseline [ Time Frame: 13 weeks, 26 weeks, 1 yr, 18 months, 2 yrs, 3 yrs, 4 yrs, 5 yrs ]


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02036853


Contacts
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Contact: Dianna Grado, RN, CRC 682-885-2844 Dianna.Grado@cookchildrens.org

Locations
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United States, Texas
Cook Childrens Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Contact: Dianna Grado, RN, CRC    682-885-2844    Dianna.Grado@cookchildrens.org   
Contact: Laurie Bailey, PhD    682-885-2488    Laurie.Bailey@CookChildrens.org   
Principal Investigator: Adrian Lacy, MD         
Sponsors and Collaborators
Adrian Lacy
Ultragenyx Pharmaceutical Inc
Investigators
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Principal Investigator: Adrian Lacy, MD Cook Children's Medical Center

Publications:
Ataíde TdaR, de Olivera SK, da Silva FM, Vitorino Filha LGC, do N Tavares MC, Sant'Ana AEG. Toxicological analysis of the chronic consumption of diheptanoin and triheptanoin in rats. Intl J Food Sci Tech. 2009;44:484-492
Goldstein A, Barone AR, DeWard SJ, Payne N, Vockley J. Triheptanoin therapy for inherited disorders of fatty acid oxidation. Mitochondrion. 2012;12(5):566
Sparrow, SS, Cicchetti D, & Balla DA. Vineland Adaptive Behavior Scales - 2nd Edition manual. Minneapolis, MN: NCS Pearson, Inc; 2005

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Responsible Party: Adrian Lacy, Principal Investigator, Cook Children's Health Care System
ClinicalTrials.gov Identifier: NCT02036853    
Other Study ID Numbers: 2013-NEUR-001
First Posted: January 15, 2014    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018
Keywords provided by Adrian Lacy, Cook Children's Health Care System:
Triheptanoin
Glut1 DS
Epilepsy
Seizures
Additional relevant MeSH terms:
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Carbohydrate Metabolism, Inborn Errors
Syndrome
Disease
Pathologic Processes
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases