GLUT1DS: An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome
Sponsor
Adrian Lacy (Other)
Overall Status
Completed
CT.gov ID
NCT02036853
Collaborator
Ultragenyx Pharmaceutical Inc (Industry)
20
1
2
64.3
0.3
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
20 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
:
Feb 20, 2014
Actual Primary Completion Date
:
Jun 30, 2019
Actual Study Completion Date
:
Jun 30, 2019
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Reported Change in Seizures Frequency From Baseline at 13 Weeks [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 [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 [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 [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 [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 [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 [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 [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
1 Year
to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cook Childrens Medical Center | Fort Worth | Texas | United States | 76104 |
Sponsors and Collaborators
- Adrian Lacy
- Ultragenyx Pharmaceutical Inc
Investigators
- Principal Investigator: Adrian Lacy, MD, Cook Children's Medical Center
Study Documents (Full-Text)
More Information
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
- 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.
- Baruteau J, Sachs P, Broué 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.
- 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.
- Goldstein A, Barone AR, DeWard SJ, Payne N, Vockley J. Triheptanoin therapy for inherited disorders of fatty acid oxidation. Mitochondrion. 2012;12(5):566
- 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.
- 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. Review.
- 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.
- 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. Epub 2006 May 16.
- 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.
- 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.
- 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. Review.
- 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.
- 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. Review.
- 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.
- Roe CR. Inherited disorders of mitochondrial fatty acid oxidation: a new responsibility for the neonatologist. Semin Neonatol. 2002 Feb;7(1):37-47. Review.
- 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.
- Sparrow, SS, Cicchetti D, & Balla DA. Vineland Adaptive Behavior Scales - 2nd Edition manual. Minneapolis, MN: NCS Pearson, Inc; 2005
- 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.
- 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.
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:
Jan 15, 2014
Last Update Posted:
Jan 28, 2021
Last Verified:
Jan 1, 2021
Keywords provided by Adrian Lacy,
Principal Investigator,
Cook Children's Health Care System
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Between February 2014 and February 2019, 20 subjects enrolled on this study. Enrollment occured in the outpatient specialty clinic offices. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Period Title: Overall Study | ||
| STARTED | 6 | 14 |
| COMPLETED | 6 | 8 |
| NOT COMPLETED | 0 | 6 |
Baseline Characteristics
| Arm/Group Title | Schedule A | Schedule B | Total |
|---|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. | Total of all reporting groups |
| Overall Participants | 6 | 14 | 20 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
14.82
(9.77)
|
5.49
(3.09)
|
8.29
(7.13)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
33.3%
|
6
42.9%
|
8
40%
|
| Male |
4
66.7%
|
8
57.1%
|
12
60%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
1
16.7%
|
4
28.6%
|
5
25%
|
| Not Hispanic or Latino |
5
83.3%
|
10
71.4%
|
15
75%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
| White |
6
100%
|
14
100%
|
20
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Seizure Count per Reporting Period (seizures) [Mean (Full Range) ] | |||
| Mean (Full Range) [seizures] |
23.8
|
170.7
|
127.5
|
| Barry Albright Dystonia Scale (units on a scale) [Mean (Full Range) ] | |||
| Mean (Full Range) [units on a scale] |
8.5
|
7.8
|
8
|
| PedsQL Physical Health Summary Score (units on a scale) [Mean (Full Range) ] | |||
| Mean (Full Range) [units on a scale] |
48.1
|
70.8
|
55.26
|
| PedsQL Psychosocial Health Summary Score (units on a scale) [Mean (Full Range) ] | |||
| Mean (Full Range) [units on a scale] |
64.7
|
78.6
|
69.1
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed over time reflects both subject drop out and subjects that failed to record seizure counts during the respective reporting period. |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Measure Participants | 5 | 12 |
| Mean (Full Range) [seizures/two weeks] |
4.4
|
189.5
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed over time reflects both subject drop out and subjects that failed to record seizure counts during the respective reporting period. |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Measure Participants | 5 | 6 |
| Mean (Full Range) [seizures/two weeks] |
-5.6
|
-78
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed over time reflects both subject drop out and subjects that failed to record seizure counts during the respective reporting period. |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Measure Participants | 4 | 6 |
| Mean (Full Range) [seizures/two weeks] |
-6.5
|
-110.5
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed over time reflects both subject drop out and subjects that failed to record seizure counts during the respective reporting period. |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Measure Participants | 5 | 6 |
| Mean (Full Range) [seizures/two weeks] |
-5.8
|
-112.7
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed over time reflects both subject drop out and subjects that failed to record seizure counts during the respective reporting period. |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Measure Participants | 4 | 4 |
| Mean (Full Range) [seizures/two weeks] |
-6
|
-61.25
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed over time reflects both subject drop out and subjects that failed to record seizure counts during the respective reporting period. |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Measure Participants | 4 | 3 |
| Mean (Full Range) [seizures/two weeks] |
-0.8
|
-77
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed over time reflects both subject drop out and subjects that failed to record seizure counts during the respective reporting period. |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Measure Participants | 3 | 3 |
| Mean (Full Range) [seizures/two weeks] |
-8.3
|
-80.3
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed over time reflects both subject drop out and subjects that failed to record seizure counts during the respective reporting period. |
| Arm/Group Title | Schedule A | Schedule B |
|---|---|---|
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. |
| Measure Participants | 1 | 0 |
| Mean (Full Range) [seizures/two weeks] |
23
|
Adverse Events
| Time Frame | Adverse Event data were collected for the duration of study participation for each subject from baseline through study completion or discontinuation. The longest subject participation was 5 years, 3 months. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Schedule A | Schedule B | ||
| Arm/Group Description | Subjects previously treated with triheptanoin 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. | Naïve to triheptanoin 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. | ||
All Cause Mortality |
||||
| Schedule A | Schedule B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 0/14 (0%) | ||
Serious Adverse Events |
||||
| Schedule A | Schedule B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 1/14 (7.1%) | ||
| Nervous system disorders | ||||
| Prolonged generalized tonic-clonic seizure | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Status Epilepticus | 0/6 (0%) | 0 | 1/14 (7.1%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| Schedule A | Schedule B | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 14/14 (100%) | ||
| Ear and labyrinth disorders | ||||
| Otalgia | 1/6 (16.7%) | 1 | 1/14 (7.1%) | 1 |
| Endocrine disorders | ||||
| Hirsutism | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Eye disorders | ||||
| Conjuctivitis | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal Discomfort | 1/6 (16.7%) | 1 | 8/14 (57.1%) | 8 |
| Abdominal Distention | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Constipation | 1/6 (16.7%) | 1 | 2/14 (14.3%) | 3 |
| Diarrhea | 5/6 (83.3%) | 7 | 12/14 (85.7%) | 14 |
| Emesis | 1/6 (16.7%) | 1 | 11/14 (78.6%) | 19 |
| Flatulence | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Gastric Reflux | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Gastroenteritis | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Nausea | 1/6 (16.7%) | 1 | 3/14 (21.4%) | 3 |
| Rectal Leakage | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Teething | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Tongue Pain | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| General disorders | ||||
| Fatigue | 0/6 (0%) | 0 | 3/14 (21.4%) | 3 |
| Fever | 2/6 (33.3%) | 3 | 5/14 (35.7%) | 6 |
| Lethargy | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Infections and infestations | ||||
| Abcess | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Acute Pharyngitis | 0/6 (0%) | 0 | 2/14 (14.3%) | 3 |
| Acute Tonsillitis | 0/6 (0%) | 0 | 1/14 (7.1%) | 2 |
| Acute Viral Syndrome | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Croup | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Impetigo | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Influenza | 0/6 (0%) | 0 | 3/14 (21.4%) | 5 |
| Onychomycosis | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Otitis Media | 0/6 (0%) | 0 | 5/14 (35.7%) | 5 |
| Rhinovirus | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Sinusitis | 0/6 (0%) | 0 | 2/14 (14.3%) | 2 |
| Stomach Virus | 2/6 (33.3%) | 2 | 1/14 (7.1%) | 1 |
| Strep Throat | 0/6 (0%) | 0 | 3/14 (21.4%) | 3 |
| Virus | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Fall-Witnessed | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Fracture Of Left Wrist | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Head Injury | 0/6 (0%) | 0 | 2/14 (14.3%) | 2 |
| Nasal Fracture | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Right Arm Fracture | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Right Hand Index And Middle Finger Buckle Fracture | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Right Wrist Fracture | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Investigations | ||||
| Decreased Hematocrit | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Elevated ALT | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Increased Ast | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Weight Gain | 1/6 (16.7%) | 1 | 5/14 (35.7%) | 5 |
| Weight Loss | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Decrease Carbondioxide | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Decreased Serum Carbon Dioxide | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 1/6 (16.7%) | 1 | 9/14 (64.3%) | 11 |
| Electrolyte Imbalance | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Hand Pain | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Muscle Cramps | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Nervous system disorders | ||||
| Balance Issues | 0/6 (0%) | 0 | 1/14 (7.1%) | 3 |
| Blurred Vision | 0/6 (0%) | 0 | 1/14 (7.1%) | 2 |
| Convulsive Seizures | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Headache | 2/6 (33.3%) | 2 | 4/14 (28.6%) | 4 |
| Impulsive Behavior | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Increased Seizures | 0/6 (0%) | 0 | 2/14 (14.3%) | 2 |
| Lost Ability To Independently Walk | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Poor Balance | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Seizure | 1/6 (16.7%) | 1 | 1/14 (7.1%) | 1 |
| Somnolence | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Worsening Paroxysmal Exercise Dyskinesia | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Psychiatric disorders | ||||
| Aggression | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Agitation | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Excessive Daytime Sleepiness | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Hyperactivity | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Hyperactivity (Adhd) | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Inattention | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Insomnia | 1/6 (16.7%) | 1 | 2/14 (14.3%) | 2 |
| Moodiness | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Sleep Difficulties | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Renal and urinary disorders | ||||
| Incontinence | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Urinary Incontinence | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Amenorrhea | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute Bronchitis | 0/6 (0%) | 0 | 1/14 (7.1%) | 2 |
| Rhinorrhea | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Seasonal Allergies | 0/6 (0%) | 0 | 2/14 (14.3%) | 2 |
| Upper Respiratory Infection | 1/6 (16.7%) | 1 | 2/14 (14.3%) | 2 |
| Viral Upper Respiratory Infection | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Cellulitis | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Chin Laceration | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Rash-Right Leg | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Scalp Laceration | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
| Skin Scale Hands | 1/6 (16.7%) | 1 | 0/14 (0%) | 0 |
| Vascular disorders | ||||
| Contusion of Left Foot | 0/6 (0%) | 0 | 1/14 (7.1%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Director of Research Operations |
|---|---|
| Organization | Cook Children's Health Care System |
| Phone | 682-885-2103 |
| CookChildrensResearch@cookchildrens.org |
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:
Jan 15, 2014
Last Update Posted:
Jan 28, 2021
Last Verified:
Jan 1, 2021