EpilepsyPhase 1NCT03041363
Treatment Development of Triheptanoin (G1D)
A Phase 1 study testing Triheptanoin in people with Epilepsy and GLUT1DS1, run by Juan Pascual at 1 site in United States.
Trial summary
To determine the maximum tolerated dose (MTD), as a percentage of calories consumed, of triheptanoin (C7 oil; C7) in a pediatric and adult patient population genetically diagnosed with glucose transporter type 1 deficiency disorder (G1D). Read more about this study
- Who is it for?
- Ages 2 to 35 years
- Conditions the study is for
- Epilepsy, GLUT1DS1, Glut1 Deficiency Syndrome 1, Autosomal Recessive
- What is being tested?
- Triheptanoin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Mar 2017to 22 Dec 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of glucose transporter type I deficiency (G1D) confirmed by genotyping or PET scan of the brain.
- Stable on no dietary therapy other than Modified Atkins diet (i.e., on no dietary therapy for 1 month, including, but not limited to, medium chain triglyceride therapy).
- Males and females 2 years 6 months to 35 years 11 months old, inclusive.
Who cannot join
- Subjects with a history of life-threatening seizure episodes, including but not limited to status epilepticus and cardiac arrest.
- Subjects with evidence of independent, unrelated metabolic and/or genetic disease.
- Subjects with a body mass index (BMI) greater than or equal to 30.
- Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome, Crohn's disease, or colitis, which could increase the subject's risk of developing diarrhea or stomach pain.
- Subjects currently on dietary therapy (i.e., ketogenic diet, medium chain triglyceride-supplemented diets, Atkins diet, low glycemic index diet, and related diets).
- Women who are pregnant or breast-feeding may not participate.
Show all 15Show fewer
- Women who plan to become pregnant during the course of the study, or who are unwilling to use birth control to prevent pregnancy (including abstinence) may not participate.
- Females age 10 and over will be asked to provide a urine sample for a pregnancy test via dipstick.
- Subjects will be asked to agree to abstinence or another form of birth control for the duration of the study.
- Allergy/sensitivity to C7.
- Previous treatment with C7 one month prior to enrollment.
- Treatment with medium chain triglycerides in the last 30 days.
- Subjects exhibiting signs of dementia, or diagnosed with any degenerative brain disorder (such as Alzheimer's disease) that would confound assessment of cognitive changes, in the opinion of the investigator.
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- Inability or unwillingness of 1 parent or legal guardian/representative to give written informed consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment Development of Triheptanoin (C7) for Glucose Transporter Type I Deficiency (G1D): A Phase I Maximum Tolerable Dose Trial
To determine the maximum tolerated dose (MTD), as a percentage of calories consumed, of triheptanoin (C7 oil; C7) in a pediatric and adult patient population genetically diagnosed with glucose transporter type 1 deficiency disorder (G1D).
Read the detailed description
The trial will use an open-label, standard 3+3 phase I design for determining the MTD of orally-administered C7 in G1D.
Triheptanoin: a triglyceride oil containing three odd-carbon chain-length fatty acids (i.e., a triglyceride of 7-carbon heptanoic acid). Triheptanoin will be taken 4 times per day (approximately every 6 hours) by mouth. it is dosed 4 times per day, divided evenly, and the total C7 daily dose will re-place 40% or 45% (depending on group) of the daily caloric intake from fat in the usual diet, based on current protocol guidelines. The oil should be taken approximately one hour before meals, and will be mixed with fat-free, sugar-free yogurt or pudding for administration.
Up to thirty-six subjects will be enrolled in a 10-day maximum tolerable dose trial of C7. Initiation of C7 dosing will be conducted in the Children's Medical Center Dallas ambulatory Care Pavilion neurology Clinic. Subjects will be provided with C7 oil to take over the 7 days of administration.
Subjects will not be required to stop other medications. Subjects will be directed to maintain their usual medications, including rescue seizure medications, as necessary for the course of the study. Subjects may have any clinical medical records transferred back to their referring physician at completion of the study.
- Conditions
- Epilepsy, GLUT1DS1, Glut1 Deficiency Syndrome 1, Autosomal Recessive, Glucose Metabolism Disorders, Glucose Transport Defect, Glucose Transporter Type 1 Deficiency Syndrome
- Being tested
- Triheptanoin
- Medical subject headings
- Epilepsy, Glucose Metabolism Disorders, Glycogen Storage Disease Id, Glut1 Deficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TriheptanoinDrug
Also called C7
Triheptanoin will be administered for 7 days 4 times daily.
| Study group | Role | What they receive |
|---|---|---|
| Triheptanoin | Experimental | Dose 1 C7 administered as 40% daily caloric intake. Dose 2. C7 administered as 45% daily caloric intake. Receives: Drug: Triheptanoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose trial
To determine the MTD as a percentage of calories consumed in pediatric and adult patient population.
Measured: medication taken daily for 7 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2017 (estimated)
- Study start29 Mar 2017
- Primary completion22 Dec 2017
- Study completion22 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The trial will use an open-label, standard 3+3 phase 1 design for determining the MTD of orally administered C7 in G1D.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Juan Pascual
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Juan Pascual, University of Texas Southwestern Medical Center
- Investigators
- Juan Pascual, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03041363
- Sponsor's protocol ID
- STU 062016-105
- Other IDs
- R01NS094257
- Status last verified
- Dec 2022
- First submitted
- 31 Jan 2017
- Last updated
- 22 Dec 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pascual JM, Liu P, Mao D, Kelly DI, Hernandez A, Sheng M, Good LB, Ma Q, Marin-Valencia I, Zhang X, Park JY, Hynan LS, Stavinoha P, Roe CR, Lu H. Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. JAMA Neurol. 2014 Oct;71(10):1255-65. doi: 10.1001/jamaneurol.2014.1584.
PubMed 25110966Marin-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.
PubMed 23072752Pascual JM, Ronen GM. Glucose Transporter Type I Deficiency (G1D) at 25 (1990-2015): Presumptions, Facts, and the Lives of Persons With This Rare Disease. Pediatr Neurol. 2015 Nov;53(5):379-93. doi: 10.1016/j.pediatrneurol.2015.08.001. Epub 2015 Aug 10.
PubMed 26341673Malaga I, Avila A, Primeaux S, Kallem RR, Roe CR, Putnam WC, Park JY, Shinnar S, Ahn C, Pascual JM. Maximum dose, safety, tolerability and ketonemia after triheptanoin in glucose transporter type 1 deficiency (G1D). Sci Rep. 2023 Mar 1;13(1):3465. doi: 10.1038/s41598-023-30578-z.
PubMed 36859467
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Development of Triheptanoin (C7) for Glucose Transporter Type I Deficiency (G1D): A Phase I Maximum Tolerable Dose Trial
- ClinicalTrials.gov ID
- NCT03041363
- Acronym / sponsor ID
- STU 062016-105
- Conditions
- Epilepsy, GLUT1DS1, Glut1 Deficiency Syndrome 1, Autosomal Recessive, Glucose Metabolism Disorders, Glucose Transport Defect, Glucose Transporter Type 1 Deficiency Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Juan PascualUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- 29 Mar 2017 (actual)
- Primary completion
- 22 Dec 2017 (actual)
- Study completion
- 22 Dec 2017 (actual)
- First posted
- 2 Feb 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To determine the maximum tolerated dose (MTD), as a percentage of calories consumed, of triheptanoin (C7 oil; C7) in a pediatric and adult patient population genetically diagnosed with glucose transporter type 1 deficiency disorder (G1D).
Detailed description
The trial will use an open-label, standard 3+3 phase I design for determining the MTD of orally-administered C7 in G1D.
Triheptanoin: a triglyceride oil containing three odd-carbon chain-length fatty acids (i.e., a triglyceride of 7-carbon heptanoic acid). Triheptanoin will be taken 4 times per day (approximately every 6 hours) by mouth. it is dosed 4 times per day, divided evenly, and the total C7 daily dose will re-place 40% or 45% (depending on group) of the daily caloric intake from fat in the usual diet, based on current protocol guidelines. The oil should be taken approximately one hour before meals, and will be mixed with fat-free, sugar-free yogurt or pudding for administration.
Up to thirty-six subjects will be enrolled in a 10-day maximum tolerable dose trial of C7. Initiation of C7 dosing will be conducted in the Children's Medical Center Dallas ambulatory Care Pavilion neurology Clinic. Subjects will be provided with C7 oil to take over the 7 days of administration.
Subjects will not be required to stop other medications. Subjects will be directed to maintain their usual medications, including rescue seizure medications, as necessary for the course of the study. Subjects may have any clinical medical records transferred back to their referring physician at completion of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The trial will use an open-label, standard 3+3 phase 1 design for determining the MTD of orally administered C7 in G1D.
| Arm | Type | Receives |
|---|---|---|
| Triheptanoin | Experimental | Drug: TriheptanoinDose 1 C7 administered as 40% daily caloric intake. Dose 2. C7 administered as 45% daily caloric intake. |
Who may qualify
- Ages
- 2 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Diagnosis of glucose transporter type I deficiency (G1D) confirmed by genotyping or PET scan of the brain.
- Stable on no dietary therapy other than Modified Atkins diet (i.e., on no dietary therapy for 1 month, including, but not limited to, medium chain triglyceride therapy).
- Males and females 2 years 6 months to 35 years 11 months old, inclusive.
Key exclusion criteria (15 listed)
- Subjects with a history of life-threatening seizure episodes, including but not limited to status epilepticus and cardiac arrest.
- Subjects with evidence of independent, unrelated metabolic and/or genetic disease.
- Subjects with a body mass index (BMI) greater than or equal to 30.
- Subjects with a chronic gastrointestinal disorder, such as irritable bowel syndrome, Crohn's disease, or colitis, which could increase the subject's risk of developing diarrhea or stomach pain.
- Subjects currently on dietary therapy (i.e., ketogenic diet, medium chain triglyceride-supplemented diets, Atkins diet, low glycemic index diet, and related diets).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TriheptanoinAlso: C7Triheptanoin will be administered for 7 days 4 times daily. | Drug | Triheptanoin |
Primary outcome
Maximum tolerated dose trial
Time frame: medication taken daily for 7 days.
To determine the MTD as a percentage of calories consumed in pediatric and adult patient population.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2022.
- Background: PubMed 25110966Pascual JM, Liu P, Mao D, Kelly DI, Hernandez A, Sheng M, Good LB, Ma Q, Marin-Valencia I, Zhang X, Park JY, Hynan LS, Stavinoha P, Roe CR, Lu H. Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. JAMA Neurol. 2014 Oct;71(10):1255-65. doi: 10.1001/jamaneurol.2014.1584.
- Background: PubMed 23072752Marin-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.
- Background: PubMed 26341673Pascual JM, Ronen GM. Glucose Transporter Type I Deficiency (G1D) at 25 (1990-2015): Presumptions, Facts, and the Lives of Persons With This Rare Disease. Pediatr Neurol. 2015 Nov;53(5):379-93. doi: 10.1016/j.pediatrneurol.2015.08.001. Epub 2015 Aug 10.
- Derived from this study: PubMed 36859467Malaga I, Avila A, Primeaux S, Kallem RR, Roe CR, Putnam WC, Park JY, Shinnar S, Ahn C, Pascual JM. Maximum dose, safety, tolerability and ketonemia after triheptanoin in glucose transporter type 1 deficiency (G1D). Sci Rep. 2023 Mar 1;13(1):3465. doi: 10.1038/s41598-023-30578-z.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juan Pascual principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Triheptanoin in people with Epilepsy and GLUT1DS1, run by Juan Pascual at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose trial (time frame: medication taken daily for 7 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03041363, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2022.