Glucose Transporter Type 1 Deficiency SyndromePhase 1/2NCT02021526
Triheptanoin (C7 Oil), a Food Supplement, for Glucose Transporter Type I Deficiency (G1D)
A Phase 1/2 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
This is a single-site, open-label, phase II trial of C7, a food supplement or medical food, for the development of treatment outcome measures for glucose transporter type I deficiency (G1D). The primary outcome measures are: 1. Read more about this study
- Who is it for?
- Ages 30 months to 55 years
- 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
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2015to Jun 2020
- Phase
- Phase 1/2
- 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 30 months to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis or suspected diagnosis of glucose transporter type I deficiency (G1D).
- On stable ketogenic diet at a ratio between 1:2.5 and 1:4 OR Stable on no dietary therapy
- Males and females 30 months to 55 years 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 a BMI (body mass index) greater than or equal to 30 will be excluded.
- Subjects currently on dietary therapy other than ketogenic diet (i.e., medium chain triglyceride-supplemented diets, Atkins diet, low glycemic index diet, etc.).
- Women who are pregnant or breast-feeding may not participate. 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.
- Allergy/sensitivity to triheptanoin.
- Previous treatment with triheptanoin.
Show all 11Show fewer
- 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.
- Patients with metal implants, experience claustrophobia, or who are behaviorally unable to be still for MRS (magnetic resonance spectroscopy) imaging (not due to seizures) will be excluded from the imaging portion of the research.
- Inability or unwillingness of subject or legal guardian/representative to give written informed consent, or assent for children age 10-17.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment Development of Triheptanoin for Glucose Transporter Type I Deficiency
This is a single-site, open-label, phase II trial of C7, a food supplement or medical food, for the development of treatment outcome measures for glucose transporter type I deficiency (G1D). The primary outcome measures are: 1. Safety and tolerability of C7 as measured by changes in comprehensive blood work, including lipid and free fatty acid panels, self-reported side effects and clinical exam; 2. Changes in brain metabolic rate by MRI and EEG measurements during C7 treatment; and 3. Maintenance of ketosis in G1D patients on ketogenic diet, as measured by serial ketone levels during treatment initiation.
- Being tested
- Triheptanoin
- Keywords
- G1D, Glut1 Deficiency, Glucose Transporter Type 1 Deficiency, Glucose Transporter Type I Deficiency
- 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, Heptanoic Acid
Triheptanoin (C7 oil) is a 7-carbon medium chain triglyceride.
| Study group | Role | What they receive |
|---|---|---|
| No Dietary Therapy | Experimental | Patients currently on no dietary therapy will receive triheptanoin (C7 oil), dosed at 1 g/kg body weight and divided into 4 doses daily, administered for 6 months Receives: Drug: Triheptanoin |
| Ketogenic Diet | Experimental | Patients on ketogenic diet will receive triheptanoin (C7 oil) in place of their usual fat intake, at a dose sufficient to maintain their ketogenic diet ratio (based on patient weight and current ratio). Patients will receive triheptanoin for 6 months. Receives: Drug: Triheptanoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in risk for Metabolic Syndrome
Triglycerides, lipid levels, and cholesterol are measured to evaluate change in risk of metabolic syndrome
Measured: Baseline, 6 months, 9 months
Change on Biomarkers
EEG and brain metabolic rate will be measured at three time points. Changes in these biomarkers indicate the utilization of triheptanoin in brain metabolism
Measured: Baseline, 6 months, 9 months
Change in Ketosis
Safety blood work (described in the first outcome measure) is measured along with ketone levels and EEG to confirm that triheptanoin is safe and does not break ketosis in patients on the ketogenic diet
Measured: baseline, 6 months, 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2013 (estimated)
- Study startDec 2015
- Primary completionJun 2020 (estimated)
- Study completionJun 2020 (estimated)
Why it stopped: NIH funding resulted in new clinical trial
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (25)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 1/2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 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, MD, PhD, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02021526
- Sponsor's protocol ID
- PASCG1D2014
- Status last verified
- Feb 2019
- First submitted
- 12 Dec 2013
- Last updated
- 15 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
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 22683290Jeffrey FM, Marin-Valencia I, Good LB, Shestov AA, Henry PG, Pascual JM, Malloy CR. Modeling of brain metabolism and pyruvate compartmentation using (13)C NMR in vivo: caution required. J Cereb Blood Flow Metab. 2013 Aug;33(8):1160-7. doi: 10.1038/jcbfm.2013.67. Epub 2013 May 8.
PubMed 23652627Xu F, Liu P, Pascual JM, Xiao G, Lu H. Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation, and oxidative metabolism. J Cereb Blood Flow Metab. 2012 Oct;32(10):1909-18. doi: 10.1038/jcbfm.2012.93. Epub 2012 Jun 27.
PubMed 22739621Marin-Valencia I, Good LB, Ma Q, Jeffrey FM, Malloy CR, Pascual JM. High-resolution detection of (1)(3)C multiplets from the conscious mouse brain by ex vivo NMR spectroscopy. J Neurosci Methods. 2012 Jan 15;203(1):50-5. doi: 10.1016/j.jneumeth.2011.09.006. Epub 2011 Sep 17.
PubMed 21946227Marin-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 20598931Perez-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, 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, 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. [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 15152356
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Development of Triheptanoin for Glucose Transporter Type I Deficiency
- ClinicalTrials.gov ID
- NCT02021526
- Acronym / sponsor ID
- PASCG1D2014
- Keywords
- G1D, Glut1 Deficiency, Glucose Transporter Type 1 Deficiency, Glucose Transporter Type I Deficiency
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: NIH funding resulted in new clinical trial
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Juan PascualUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- Jun 2020 (estimated)
- Study completion
- Jun 2020 (estimated)
- First posted
- 27 Dec 2013 (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.
This is a single-site, open-label, phase II trial of C7, a food supplement or medical food, for the development of treatment outcome measures for glucose transporter type I deficiency (G1D). The primary outcome measures are: 1. Safety and tolerability of C7 as measured by changes in comprehensive blood work, including lipid and free fatty acid panels, self-reported side effects and clinical exam; 2. Changes in brain metabolic rate by MRI and EEG measurements during C7 treatment; and 3. Maintenance of ketosis in G1D patients on ketogenic diet, as measured by serial ketone levels during treatment initiation.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No Dietary Therapy | Experimental | Drug: TriheptanoinPatients currently on no dietary therapy will receive triheptanoin (C7 oil), dosed at 1 g/kg body weight and divided into 4 doses daily, administered for 6 months |
| Ketogenic Diet | Experimental | Drug: TriheptanoinPatients on ketogenic diet will receive triheptanoin (C7 oil) in place of their usual fat intake, at a dose sufficient to maintain their ketogenic diet ratio (based on patient weight and current ratio). Patients will receive triheptanoin for 6 months. |
Who may qualify
- Ages
- 30 months to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Diagnosis or suspected diagnosis of glucose transporter type I deficiency (G1D).
- On stable ketogenic diet at a ratio between 1:2.5 and 1:4 OR Stable on no dietary therapy
- Males and females 30 months to 55 years old, inclusive.
Key exclusion criteria (11 listed)
- Subjects with a history of life-threatening seizure episodes, including but not limited to status epilepticus and cardiac arrest.
- Subjects with a BMI (body mass index) greater than or equal to 30 will be excluded.
- Subjects currently on dietary therapy other than ketogenic diet (i.e., medium chain triglyceride-supplemented diets, Atkins diet, low glycemic index diet, etc.).
- Women who are pregnant or breast-feeding may not participate. 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.
- Allergy/sensitivity to triheptanoin.
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, Heptanoate, Heptanoic AcidTriheptanoin (C7 oil) is a 7-carbon medium chain triglyceride. | Drug | Ketogenic Diet, No Dietary Therapy |
Primary outcome
Change in risk for Metabolic Syndrome
Time frame: Baseline, 6 months, 9 months
Triglycerides, lipid levels, and cholesterol are measured to evaluate change in risk of metabolic syndrome
Change on Biomarkers
Time frame: Baseline, 6 months, 9 months
EEG and brain metabolic rate will be measured at three time points. Changes in these biomarkers indicate the utilization of triheptanoin in brain metabolism
Change in Ketosis
Time frame: baseline, 6 months, 9 months
Safety blood work (described in the first outcome measure) is measured along with ketone levels and EEG to confirm that triheptanoin is safe and does not break ketosis in patients on the ketogenic diet
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2019.
- 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 23652627Jeffrey FM, Marin-Valencia I, Good LB, Shestov AA, Henry PG, Pascual JM, Malloy CR. Modeling of brain metabolism and pyruvate compartmentation using (13)C NMR in vivo: caution required. J Cereb Blood Flow Metab. 2013 Aug;33(8):1160-7. doi: 10.1038/jcbfm.2013.67. Epub 2013 May 8.
- Background: PubMed 22739621Xu F, Liu P, Pascual JM, Xiao G, Lu H. Effect of hypoxia and hyperoxia on cerebral blood flow, blood oxygenation, and oxidative metabolism. J Cereb Blood Flow Metab. 2012 Oct;32(10):1909-18. doi: 10.1038/jcbfm.2012.93. Epub 2012 Jun 27.
- Background: PubMed 21946227Marin-Valencia I, Good LB, Ma Q, Jeffrey FM, Malloy CR, Pascual JM. High-resolution detection of (1)(3)C multiplets from the conscious mouse brain by ex vivo NMR spectroscopy. J Neurosci Methods. 2012 Jan 15;203(1):50-5. doi: 10.1016/j.jneumeth.2011.09.006. Epub 2011 Sep 17.
- 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 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 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 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 17169300Pascual JM. [Glucose transport hereditary diseases]. Med Clin (Barc). 2006 Nov 11;127(18):709-14. doi: 10.1157/13095099. Spanish.
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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, 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 1/2 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 3 inclusion and 11 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: withdrawn, as of the sponsor's last update on 15 Feb 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
Change in risk for Metabolic Syndrome (time frame: Baseline, 6 months, 9 months). The study lists 3 primary outcomes in all. 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 NCT02021526, which also lists 25 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 15 Feb 2019.