Back to resultsAn Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome (GLUT1DS)
Primary Purpose
Glucose Transporter Type-1 Deficiency Syndrome (Glut1 DS)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Triheptanoin
Sponsored by
About this trial
This is an interventional treatment trial for Glucose Transporter Type-1 Deficiency Syndrome (Glut1 DS) focused on measuring Triheptanoin, Glut1 DS, Epilepsy, Seizures
Eligibility Criteria
Inclusion Criteria:
Individuals eligible to participate in this study must meet all of the following criteria:
- Patients with GLUT1 DS by physician diagnosis
- Males and females, aged 1 to 50 years
- Allowed to be on concomitant AEDs
- Patients are able to tolerate triheptanoin if they have been (or are currently being) treated with this medication
- Must, in the opinion of the investigator, be willing and able to comply with study procedures and schedule
- 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
- Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study
- 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:
- Patients and their Legally Authorized Representatives (as appropriate) not willing or able to give written or verbal assent or written informed consent.
- Concomitant administration of a ketogenic diet for the treatment of GLUT1 deficiency
- Concomitant administration of valproic acid
- In the Investigator's opinion, the patient may not be compliant
- Pregnant or breastfeeding an infant at screening
- 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
- History of or current suicidal ideation, behavior and attempts
- 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
Sites / Locations
- Cook Childrens Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Schedule A
Schedule B
Arm Description
Subjects previously treated with triheptanoin
Naïve to triheptanoin
Outcomes
Primary Outcome Measures
Reported Change in Seizures Frequency From Baseline at 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
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
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
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
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
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
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
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.
Secondary Outcome Measures
Full Information
NCT ID
NCT02036853
First Posted
January 13, 2014
Last Updated
January 26, 2021
Sponsor
Adrian Lacy
Collaborators
Ultragenyx Pharmaceutical Inc
1. Study Identification
Unique Protocol Identification Number
NCT02036853
Brief Title
An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome
Acronym
GLUT1DS
Official Title
An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome (GLUT1 DS)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
February 20, 2014 (undefined)
Primary Completion Date
June 30, 2019 (Actual)
Study Completion Date
June 30, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Adrian Lacy
Collaborators
Ultragenyx Pharmaceutical Inc
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glucose Transporter Type-1 Deficiency Syndrome (Glut1 DS)
Keywords
Triheptanoin, Glut1 DS, Epilepsy, Seizures
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Schedule A
Arm Type
Experimental
Arm Description
Subjects previously treated with triheptanoin
Arm Title
Schedule B
Arm Type
Experimental
Arm Description
Naïve to triheptanoin
Intervention Type
Drug
Intervention Name(s)
Triheptanoin
Intervention Description
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 Measure Information:
Title
Reported Change in Seizures Frequency From Baseline at 13 Weeks
Description
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.
Time Frame
Baseline and 13 weeks
Title
Reported Change in Seizures Frequency From Baseline at 26 Weeks
Description
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.
Time Frame
Baseline and 26 weeks
Title
Reported Change in Seizures Frequency From Baseline at 1 Year
Description
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.
Time Frame
Baseline and one yr
Title
Reported Change in Seizures Frequency From Baseline at 18 Months
Description
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.
Time Frame
Baseline and 18 months
Title
Reported Change in Seizures Frequency From Baseline at 2 Years
Description
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.
Time Frame
Baseline and two yrs
Title
Reported Change in Seizures Frequency From Baseline at 3 Years
Description
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.
Time Frame
Baseline and three yrs
Title
Reported Change in Seizure Frequency From Baseline at 4 Years
Description
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.
Time Frame
Baseline and four yrs
Title
Reported Change in Seizure Frequency From Baseline at 5 Years
Description
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.
Time Frame
Baseline and five yrs
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Individuals eligible to participate in this study must meet all of the following criteria:
Patients with GLUT1 DS by physician diagnosis
Males and females, aged 1 to 50 years
Allowed to be on concomitant AEDs
Patients are able to tolerate triheptanoin if they have been (or are currently being) treated with this medication
Must, in the opinion of the investigator, be willing and able to comply with study procedures and schedule
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
Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study
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:
Patients and their Legally Authorized Representatives (as appropriate) not willing or able to give written or verbal assent or written informed consent.
Concomitant administration of a ketogenic diet for the treatment of GLUT1 deficiency
Concomitant administration of valproic acid
In the Investigator's opinion, the patient may not be compliant
Pregnant or breastfeeding an infant at screening
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
History of or current suicidal ideation, behavior and attempts
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Lacy, MD
Organizational Affiliation
Cook Children's Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cook Childrens Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
11800053
Citation
Johnson W Jr; Cosmetic Ingredient Review Expert Panel. Final report on the safety assessment of trilaurin, triarachidin, tribehenin, tricaprin, tricaprylin, trierucin, triheptanoin, triheptylundecanoin, triisononanoin, triisopalmitin, triisostearin, trilinolein, trimyristin, trioctanoin, triolein, tripalmitin, tripalmitolein, triricinolein, tristearin, triundecanoin, glyceryl triacetyl hydroxystearate, glyceryl triacetyl ricinoleate, and glyceryl stearate diacetate. Int J Toxicol. 2001;20 Suppl 4:61-94.
Results Reference
background
PubMed Identifier
23443458
Citation
Pearson TS, Akman C, Hinton VJ, Engelstad K, De Vivo DC. Phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS). Curr Neurol Neurosci Rep. 2013 Apr;13(4):342. doi: 10.1007/s11910-013-0342-7.
Results Reference
background
PubMed Identifier
22812641
Citation
Pong AW, Geary BR, Engelstad KM, Natarajan A, Yang H, De Vivo DC. Glucose transporter type I deficiency syndrome: epilepsy phenotypes and outcomes. Epilepsia. 2012 Sep;53(9):1503-10. doi: 10.1111/j.1528-1167.2012.03592.x. Epub 2012 Jul 19.
Results Reference
background
PubMed Identifier
12069537
Citation
Roe CR. Inherited disorders of mitochondrial fatty acid oxidation: a new responsibility for the neonatologist. Semin Neonatol. 2002 Feb;7(1):37-47. doi: 10.1053/siny.2002.0097.
Results Reference
background
PubMed Identifier
16705058
Citation
Kinman RP, Kasumov T, Jobbins KA, Thomas KR, Adams JE, Brunengraber LN, Kutz G, Brewer WU, Roe CR, Brunengraber H. Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E860-6. doi: 10.1152/ajpendo.00366.2005. Epub 2006 May 16.
Results Reference
background
PubMed Identifier
19666922
Citation
Deng S, Zhang GF, Kasumov T, Roe CR, Brunengraber H. Interrelations between C4 ketogenesis, C5 ketogenesis, and anaplerosis in the perfused rat liver. J Biol Chem. 2009 Oct 9;284(41):27799-27807. doi: 10.1074/jbc.M109.048744. Epub 2009 Aug 8.
Results Reference
background
PubMed Identifier
19903863
Citation
Gu L, Zhang GF, Kombu RS, Allen F, Kutz G, Brewer WU, Roe CR, Brunengraber H. Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile. Am J Physiol Endocrinol Metab. 2010 Feb;298(2):E362-71. doi: 10.1152/ajpendo.00384.2009. Epub 2009 Nov 10.
Results Reference
background
PubMed Identifier
23072752
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.
Results Reference
background
PubMed Identifier
20691264
Citation
Willis S, Stoll J, Sweetman L, Borges K. Anticonvulsant effects of a triheptanoin diet in two mouse chronic seizure models. Neurobiol Dis. 2010 Dec;40(3):565-72. doi: 10.1016/j.nbd.2010.07.017. Epub 2010 Aug 4.
Results Reference
background
PubMed Identifier
18565731
Citation
Samala R, Willis S, Borges K. Anticonvulsant profile of a balanced ketogenic diet in acute mouse seizure models. Epilepsy Res. 2008 Oct;81(2-3):119-27. doi: 10.1016/j.eplepsyres.2008.05.001. Epub 2008 Jun 18.
Results Reference
background
PubMed Identifier
23196212
Citation
Kim TH, Borges K, Petrou S, Reid CA. Triheptanoin reduces seizure susceptibility in a syndrome-specific mouse model of generalized epilepsy. Epilepsy Res. 2013 Jan;103(1):101-5. doi: 10.1016/j.eplepsyres.2012.09.016. Epub 2012 Nov 26.
Results Reference
background
Citation
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
Results Reference
background
PubMed Identifier
12122118
Citation
Roe CR, Sweetman L, Roe DS, David F, Brunengraber H. Treatment of cardiomyopathy and rhabdomyolysis in long-chain fat oxidation disorders using an anaplerotic odd-chain triglyceride. J Clin Invest. 2002 Jul;110(2):259-69. doi: 10.1172/JCI15311.
Results Reference
background
PubMed Identifier
16763896
Citation
Roe CR, Mochel F. Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):332-40. doi: 10.1007/s10545-006-0290-3.
Results Reference
background
PubMed Identifier
20512158
Citation
Mochel F, Duteil S, Marelli C, Jauffret C, Barles A, Holm J, Sweetman L, Benoist JF, Rabier D, Carlier PG, Durr A. Dietary anaplerotic therapy improves peripheral tissue energy metabolism in patients with Huntington's disease. Eur J Hum Genet. 2010 Sep;18(9):1057-60. doi: 10.1038/ejhg.2010.72. Epub 2010 May 26.
Results Reference
background
PubMed Identifier
23053472
Citation
Baruteau J, Sachs P, Broue P, Brivet M, Abdoul H, Vianey-Saban C, Ogier de Baulny H. Clinical and biological features at diagnosis in mitochondrial fatty acid beta-oxidation defects: a French pediatric study of 187 patients. J Inherit Metab Dis. 2013 Sep;36(5):795-803. doi: 10.1007/s10545-012-9542-6. Epub 2012 Oct 3.
Results Reference
background
Citation
Goldstein A, Barone AR, DeWard SJ, Payne N, Vockley J. Triheptanoin therapy for inherited disorders of fatty acid oxidation. Mitochondrion. 2012;12(5):566
Results Reference
background
Citation
Sparrow, SS, Cicchetti D, & Balla DA. Vineland Adaptive Behavior Scales - 2nd Edition manual. Minneapolis, MN: NCS Pearson, Inc; 2005
Results Reference
background
PubMed Identifier
10400175
Citation
Barry MJ, VanSwearingen JM, Albright AL. Reliability and responsiveness of the Barry-Albright Dystonia Scale. Dev Med Child Neurol. 1999 Jun;41(6):404-11. doi: 10.1017/s0012162299000870.
Results Reference
background
PubMed Identifier
19807613
Citation
Varni JW, Burwinkle TM, Seid M. The PedsQL as a pediatric patient-reported outcome: reliability and validity of the PedsQL Measurement Model in 25,000 children. Expert Rev Pharmacoecon Outcomes Res. 2005 Dec;5(6):705-19. doi: 10.1586/14737167.5.6.705.
Results Reference
background
Learn more about this trial
An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome
We'll reach out to this number within 24 hrs