Glucose Transporter Type 1 Deficiency SyndromePhase 1NCT02018315
Treatment Development for Glucose Transporter Type I Deficiency Syndrome (G1D)
A Phase 1 study testing Triheptanoin in people with Glucose Transporter Type 1 Deficiency Syndrome and GLUT1 Deficiency Syndrome, run by Juan Pascual at 1 site in United States.
Trial summary
The purpose of this trial is to determine if an alternative energy source will impact brain metabolism in a disorder characterized by glucose metabolism failure in the brain. The central hypothesis tested in this investigation is whether circumventing impaired glucose metabolism is feasible, safe and potentially… Read more about this study
- Who is it for?
- Ages 1 month to 20 yearsHealthy volunteers can take part
- Conditions the study is for
- Glucose Transporter Type 1 Deficiency Syndrome, GLUT1 Deficiency Syndrome
- What is being tested?
- Triheptanoin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2012to Mar 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 month to 20 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Male or Female
- Ages 1 month to <21 years of age
- Diagnosed with glucose transporter type I deficiency.
- Age matched (within 1 year) controls not diagnosed with G1D.
Who cannot join
- All subjects carrying body metal implants incompatible with the exposure to a magnetic field
- Subjects unable to tolerate the MRI and MRS procedures due to anxiety
- Subjects receiving oxygen supplementation or those confined to a bed or stretcher
- Subjects currently receiving a ketogenic diet, due to a high risk of seizure recurrence while transitioning off ketosis.
- Patients behaviorally unable to hold still for imaging procedures (rather than limited by seizure activity) will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Clinical Trial of Citric Acid Cycle Stimulation in Energy-deficiency States: Treatment Development for Glucose Transporter Type I Deficiency Syndrome (G1D) (NMTUT 2010B)
The purpose of this trial is to determine if an alternative energy source will impact brain metabolism in a disorder characterized by glucose metabolism failure in the brain.
The central hypothesis tested in this investigation is whether circumventing impaired glucose metabolism is feasible, safe and potentially promising by supplying anaplerotic precursors through metabolism of odd-carbon fatty acids that can enter the citric acid cycle (CAC) through alternative metabolic pathways.
Read the detailed description
Triheptanoin, a nutritional supplement long used in other metabolic disorders and also added to foods and cosmetics, will be used to complement any diet that G1D patients may be receiving at enrollment with the exception of the ketogenic diet.
- Being tested
- Triheptanoin
- Keywords
- G1D, Glut1 Disorder, Glucose Transporter Type 1 Disorder, Glucose Transporter Type I Disorder
- Medical subject headings
- 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, Heptanoate
Triheptanoin is a 7-carbon medium chain triglyceride
| Study group | Role | What they receive |
|---|---|---|
| Triheptanoin | Experimental | Triheptanoin (C7 oil, liquid) dosed at 1 g/kg body weight divided and administered 4 times per day via mouth or g-tube for 3 months. Receives: Drug: Triheptanoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Reduction in Spike-wave Fraction of the EEG Recording Time
Visual analysis of EEG recording to determine the fraction of spike-range within the area of recording.
Measured: 1 day
Secondary outcomes (1)
Number of Participants With Change in Brain Metabolic Rate After 3 Months
Magnetic Resonance Imaging (MRI) used to calculate brain metabolic rate. Brain metabolic rate compared before oil ingestion (Baseline), 90 minutes after oil ingestion, and after 3 months of daily oil ingestion in each participant. Triheptanoin metabolism may lead to increased oxygen consumption only while the brain undergoes a reduction of ictogenesis. We hypothesize that when ictogenesis is abolished by triheptanoin or absent at baseline, triheptanoin exerts little or no effect on CMR02.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2013 (estimated)
- Study startJan 2012
- Primary completionJan 2013
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Glucose Transporter Type 1 Deficiency SyndromeStudies 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 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 M. Pascual, MD, PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02018315
- Sponsor's protocol ID
- UTSW 122010-186
- Status last verified
- Oct 2019
- First submitted
- 11 Dec 2013
- Last updated
- 31 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23072752Marin-Valencia I, Good LB, Ma Q, Duarte J, Bottiglieri T, Sinton CM, Heilig CW, Pascual JM. Glut1 deficiency (G1D): epilepsy and metabolic dysfunction in a mouse model of the most common human phenotype. Neurobiol Dis. 2012 Oct;48(1):92-101. doi: 10.1016/j.nbd.2012.04.011. Epub 2012 Apr 23.
PubMed 22683290Marin-Valencia I, Roe CR, Pascual JM. Pyruvate carboxylase deficiency: mechanisms, mimics and anaplerosis. Mol Genet Metab. 2010 Sep;101(1):9-17. doi: 10.1016/j.ymgme.2010.05.004. Epub 2010 Jun 9.
PubMed 20598931Wang D, Sands T, Tang M, Monani U, De Vivo D. Glucose Transporter Type 1 Deficiency Syndrome. 2002 Jul 30 [updated 2025 Mar 6]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1430/
PubMed 20301603Perez-Duenas B, Prior C, Ma Q, Fernandez-Alvarez E, Setoain X, Artuch R, Pascual JM. Childhood chorea with cerebral hypotrophy: a treatable GLUT1 energy failure syndrome. Arch Neurol. 2009 Nov;66(11):1410-4. doi: 10.1001/archneurol.2009.236.
PubMed 19901175Pascual JM, Campistol J, Gil-Nagel A. Epilepsy in inherited metabolic disorders. Neurologist. 2008 Nov;14(6 Suppl 1):S2-S14. doi: 10.1097/01.nrl.0000340787.30542.41.
PubMed 19225367Pascual JM, Wang D, Hinton V, Engelstad K, Saxena CM, Van Heertum RL, De Vivo DC. Brain glucose supply and the syndrome of infantile neuroglycopenia. Arch Neurol. 2007 Apr;64(4):507-13. doi: 10.1001/archneur.64.4.noc60165. Epub 2007 Feb 12.
PubMed 17296829Pascual JM, Wang D, Lecumberri B, Yang H, Mao X, Yang R, De Vivo DC. GLUT1 deficiency and other glucose transporter diseases. Eur J Endocrinol. 2004 May;150(5):627-33. doi: 10.1530/eje.0.1500627.
PubMed 15132717Pascual JM, Wang D, Yang R, Shi L, Yang H, De Vivo DC. Structural signatures and membrane helix 4 in GLUT1: inferences from human blood-brain glucose transport mutants. J Biol Chem. 2008 Jun 13;283(24):16732-42. doi: 10.1074/jbc.M801403200. Epub 2008 Apr 3.
PubMed 18387950Pascual JM. [Glucose transport hereditary diseases]. Med Clin (Barc). 2006 Nov 11;127(18):709-14. doi: 10.1157/13095099. Spanish.
PubMed 17169300Wang D, Pascual JM, Yang H, Engelstad K, Mao X, Cheng J, Yoo J, Noebels JL, De Vivo DC. A mouse model for Glut-1 haploinsufficiency. Hum Mol Genet. 2006 Apr 1;15(7):1169-79. doi: 10.1093/hmg/ddl032. Epub 2006 Feb 23.
PubMed 16497725Wang D, Pascual JM, Yang H, Engelstad K, Jhung S, Sun RP, De Vivo DC. Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol. 2005 Jan;57(1):111-8. doi: 10.1002/ana.20331.
PubMed 15622525Pascual JM, Lecumberri B, Wang D, Yang R, Engelstad K, De Vivo DC. [Type 1 glucose transporter (Glut1) deficiency: manifestations of a hereditary neurological syndrome]. Rev Neurol. 2004 May 1-15;38(9):860-4. Spanish.
PubMed 15152356Wang D, Pascual JM, Iserovich P, Yang H, Ma L, Kuang K, Zuniga FA, Sun RP, Swaroop KM, Fischbarg J, De Vivo DC. Functional studies of threonine 310 mutations in Glut1: T310I is pathogenic, causing Glut1 deficiency. J Biol Chem. 2003 Dec 5;278(49):49015-21. doi: 10.1074/jbc.M308765200. Epub 2003 Sep 16.
PubMed 13129919Pascual JM, Van Heertum RL, Wang D, Engelstad K, De Vivo DC. Imaging the metabolic footprint of Glut1 deficiency on the brain. Ann Neurol. 2002 Oct;52(4):458-64. doi: 10.1002/ana.10311.
PubMed 12325075
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Trial of Citric Acid Cycle Stimulation in Energy-deficiency States: Treatment Development for Glucose Transporter Type I Deficiency Syndrome (G1D) (NMTUT 2010B)
- ClinicalTrials.gov ID
- NCT02018315
- Acronym / sponsor ID
- UTSW 122010-186
- Keywords
- G1D, Glut1 Disorder, Glucose Transporter Type 1 Disorder, Glucose Transporter Type I Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Juan PascualUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Jan 2013 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 23 Dec 2013 (estimated)
- Results
- Posted 31 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this trial is to determine if an alternative energy source will impact brain metabolism in a disorder characterized by glucose metabolism failure in the brain.
The central hypothesis tested in this investigation is whether circumventing impaired glucose metabolism is feasible, safe and potentially promising by supplying anaplerotic precursors through metabolism of odd-carbon fatty acids that can enter the citric acid cycle (CAC) through alternative metabolic pathways.
Detailed description
Triheptanoin, a nutritional supplement long used in other metabolic disorders and also added to foods and cosmetics, will be used to complement any diet that G1D patients may be receiving at enrollment with the exception of the ketogenic diet.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Triheptanoin | Experimental | Drug: TriheptanoinTriheptanoin (C7 oil, liquid) dosed at 1 g/kg body weight divided and administered 4 times per day via mouth or g-tube for 3 months. |
Who may qualify
- Ages
- 1 month to 20 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Male or Female
- Ages 1 month to <21 years of age
- Diagnosed with glucose transporter type I deficiency.
- Age matched (within 1 year) controls not diagnosed with G1D.
Key exclusion criteria (5 listed)
- All subjects carrying body metal implants incompatible with the exposure to a magnetic field
- Subjects unable to tolerate the MRI and MRS procedures due to anxiety
- Subjects receiving oxygen supplementation or those confined to a bed or stretcher
- Subjects currently receiving a ketogenic diet, due to a high risk of seizure recurrence while transitioning off ketosis.
- Patients behaviorally unable to hold still for imaging procedures (rather than limited by seizure activity) will be excluded.
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: C7, HeptanoateTriheptanoin is a 7-carbon medium chain triglyceride | Drug | Triheptanoin |
Primary outcome
Number of Participants With Reduction in Spike-wave Fraction of the EEG Recording Time
Time frame: 1 day
Visual analysis of EEG recording to determine the fraction of spike-range within the area of recording.
1 secondary outcome
Number of Participants With Change in Brain Metabolic Rate After 3 Months
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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 22683290Marin-Valencia I, Good LB, Ma Q, Duarte J, Bottiglieri T, Sinton CM, Heilig CW, Pascual JM. Glut1 deficiency (G1D): epilepsy and metabolic dysfunction in a mouse model of the most common human phenotype. Neurobiol Dis. 2012 Oct;48(1):92-101. doi: 10.1016/j.nbd.2012.04.011. Epub 2012 Apr 23.
- Background: PubMed 20598931Marin-Valencia I, Roe CR, Pascual JM. Pyruvate carboxylase deficiency: mechanisms, mimics and anaplerosis. Mol Genet Metab. 2010 Sep;101(1):9-17. doi: 10.1016/j.ymgme.2010.05.004. Epub 2010 Jun 9.
- Background: PubMed 20301603Wang D, Sands T, Tang M, Monani U, De Vivo D. Glucose Transporter Type 1 Deficiency Syndrome. 2002 Jul 30 [updated 2025 Mar 6]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1430/
- Background: PubMed 19901175Perez-Duenas B, Prior C, Ma Q, Fernandez-Alvarez E, Setoain X, Artuch R, Pascual JM. Childhood chorea with cerebral hypotrophy: a treatable GLUT1 energy failure syndrome. Arch Neurol. 2009 Nov;66(11):1410-4. doi: 10.1001/archneurol.2009.236.
- Background: PubMed 19225367Pascual JM, Campistol J, Gil-Nagel A. Epilepsy in inherited metabolic disorders. Neurologist. 2008 Nov;14(6 Suppl 1):S2-S14. doi: 10.1097/01.nrl.0000340787.30542.41.
- Background: PubMed 17296829Pascual JM, Wang D, Hinton V, Engelstad K, Saxena CM, Van Heertum RL, De Vivo DC. Brain glucose supply and the syndrome of infantile neuroglycopenia. Arch Neurol. 2007 Apr;64(4):507-13. doi: 10.1001/archneur.64.4.noc60165. Epub 2007 Feb 12.
- Background: PubMed 15132717Pascual JM, Wang D, Lecumberri B, Yang H, Mao X, Yang R, De Vivo DC. GLUT1 deficiency and other glucose transporter diseases. Eur J Endocrinol. 2004 May;150(5):627-33. doi: 10.1530/eje.0.1500627.
- Background: PubMed 18387950Pascual JM, Wang D, Yang R, Shi L, Yang H, De Vivo DC. Structural signatures and membrane helix 4 in GLUT1: inferences from human blood-brain glucose transport mutants. J Biol Chem. 2008 Jun 13;283(24):16732-42. doi: 10.1074/jbc.M801403200. Epub 2008 Apr 3.
- Background: PubMed 17169300Pascual JM. [Glucose transport hereditary diseases]. Med Clin (Barc). 2006 Nov 11;127(18):709-14. doi: 10.1157/13095099. Spanish.
- Background: PubMed 16497725Wang D, Pascual JM, Yang H, Engelstad K, Mao X, Cheng J, Yoo J, Noebels JL, De Vivo DC. A mouse model for Glut-1 haploinsufficiency. Hum Mol Genet. 2006 Apr 1;15(7):1169-79. doi: 10.1093/hmg/ddl032. Epub 2006 Feb 23.
- Background: PubMed 15622525Wang D, Pascual JM, Yang H, Engelstad K, Jhung S, Sun RP, De Vivo DC. Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects. Ann Neurol. 2005 Jan;57(1):111-8. doi: 10.1002/ana.20331.
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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 M. Pascual, MD, PhD 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 Glucose Transporter Type 1 Deficiency Syndrome and GLUT1 Deficiency Syndrome, 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 4 inclusion and 5 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 31 Oct 2019. 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?
Yes. Results are posted in the registry (first posted 31 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Reduction in Spike-wave Fraction of the EEG Recording Time (time frame: 1 day). 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 NCT02018315, which also lists 18 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 31 Oct 2019.