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

Conditions

Glucose Transporter Type-1 Deficiency Syndrome (Glut1 DS)

Keywords

Triheptanoin, Glut1 DS, Epilepsy, Seizures

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.

Related papers

No related papers found yet.

Interventions

DRUGTriheptanoin

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 design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

1 Years to 50 Years

Healthy volunteers

No

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

Design outcomes

Primary

Measure	Time frame	Description
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.

Countries

United States

Participant flow

Recruitment details

Between February 2014 and February 2019, 20 subjects enrolled on this study. Enrollment occured in the outpatient specialty clinic offices.

Participants by arm

Arm	Count
Schedule A 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.	6
Schedule B 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.	14
Total	20

Withdrawals & dropouts

Period	Reason	FG001
Overall Study	Adverse Event	2
Overall Study	Lack of Efficacy	2
Overall Study	Physician Decision	1
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Total	Schedule A	Schedule B
Age, Continuous	8.29 years STANDARD_DEVIATION 7.13	14.82 years STANDARD_DEVIATION 9.77	5.49 years STANDARD_DEVIATION 3.09
Barry Albright Dystonia Scale	8 units on a scale	8.5 units on a scale	7.8 units on a scale
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants	1 Participants	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants	5 Participants	10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
PedsQL Physical Health Summary Score	55.26 units on a scale	48.1 units on a scale	70.8 units on a scale
PedsQL Psychosocial Health Summary Score	69.1 units on a scale	64.7 units on a scale	78.6 units on a scale
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	20 Participants	6 Participants	14 Participants
Seizure Count per Reporting Period	127.5 seizures	23.8 seizures	170.7 seizures
Sex: Female, Male Female	8 Participants	2 Participants	6 Participants
Sex: Female, Male Male	12 Participants	4 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 14
other Total, other adverse events	6 / 6	14 / 14
serious Total, serious adverse events	0 / 6	1 / 14

Outcome results

Primary

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.

Time frame: Baseline and four yrs