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Triheptanoin (C7 Oil), a Food Supplement, for Glucose Transporter Type I Deficiency (G1D)

Primary Purpose

Glucose Transporter Type 1 Deficiency Syndrome, Glut1 Deficiency Syndrome

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Triheptanoin

About this trial

This is an interventional basic science trial for Glucose Transporter Type 1 Deficiency Syndrome focused on measuring G1D, Glut1 Deficiency, Glucose Transporter Type 1 Deficiency, Glucose Transporter Type I Deficiency

Eligibility Criteria

30 Months - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
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.

Sites / Locations

UT Southwestern Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

No Dietary Therapy

Ketogenic Diet

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Change in risk for Metabolic Syndrome

Triglycerides, lipid levels, and cholesterol are measured to evaluate change in risk of metabolic syndrome

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

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

Secondary Outcome Measures

Full Information

NCT ID

NCT02021526

First Posted

December 12, 2013

Last Updated

February 12, 2019

Sponsor

Juan Pascual

1. Study Identification

Unique Protocol Identification Number

NCT02021526

Brief Title

Triheptanoin (C7 Oil), a Food Supplement, for Glucose Transporter Type I Deficiency (G1D)

Official Title

Treatment Development of Triheptanoin for Glucose Transporter Type I Deficiency

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Withdrawn

Why Stopped

NIH funding resulted in new clinical trial

Study Start Date

December 2015 (undefined)

Primary Completion Date

June 2020 (Anticipated)

Study Completion Date

June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Juan Pascual

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glucose Transporter Type 1 Deficiency Syndrome, Glut1 Deficiency Syndrome

Keywords

G1D, Glut1 Deficiency, Glucose Transporter Type 1 Deficiency, Glucose Transporter Type I Deficiency

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

No Dietary Therapy

Arm Type

Experimental

Arm Description

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

Arm Title

Ketogenic Diet

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Triheptanoin

Other Intervention Name(s)

C7, Heptanoate, Heptanoic Acid

Intervention Description

Triheptanoin (C7 oil) is a 7-carbon medium chain triglyceride.

Primary Outcome Measure Information:

Title

Change in risk for Metabolic Syndrome

Description

Triglycerides, lipid levels, and cholesterol are measured to evaluate change in risk of metabolic syndrome

Time Frame

Baseline, 6 months, 9 months

Title

Change on Biomarkers

Description

EEG and brain metabolic rate will be measured at three time points. Changes in these biomarkers indicate the utilization of triheptanoin in brain metabolism

Time Frame

Baseline, 6 months, 9 months

Title

Change in Ketosis

Description

Time Frame

baseline, 6 months, 9 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Months

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Juan Pascual, MD, PhD

Organizational Affiliation

UT Southwestern Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

UT Southwestern Medical Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75390

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23072752

Citation

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.

Results Reference

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PubMed Identifier

22683290

Citation

Marin-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.

Results Reference

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PubMed Identifier

23652627

Citation

Jeffrey 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.

Results Reference

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PubMed Identifier

22739621

Citation

Xu 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.

Results Reference

background

PubMed Identifier

21946227

Citation

Marin-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.

Results Reference

background

PubMed Identifier

20598931

Citation

Marin-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.

Results Reference

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PubMed Identifier

19901175

Citation

Perez-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.

Results Reference

background

PubMed Identifier

19225367

Citation

Pascual 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.

Results Reference

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PubMed Identifier

15132717

Citation

Pascual 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.

Results Reference

background

PubMed Identifier

18387950

Citation

Pascual 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.

Results Reference

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PubMed Identifier

17296829

Citation

Pascual 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.

Results Reference

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PubMed Identifier

17169300

Citation

Pascual JM. [Glucose transport hereditary diseases]. Med Clin (Barc). 2006 Nov 11;127(18):709-14. doi: 10.1157/13095099. Spanish.

Results Reference

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PubMed Identifier

16497725

Citation

Wang 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.

Results Reference

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PubMed Identifier

15622525

Citation

Wang 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.

Results Reference

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PubMed Identifier

15152356

Citation

Pascual 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.

Results Reference

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PubMed Identifier

13129919

Citation

Wang 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.

Results Reference

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PubMed Identifier

12325075

Citation

Pascual 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.

Results Reference

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PubMed Identifier

12032147

Citation

Iserovich P, Wang D, Ma L, Yang H, Zuniga FA, Pascual JM, Kuang K, De Vivo DC, Fischbarg J. Changes in glucose transport and water permeability resulting from the T310I pathogenic mutation in Glut1 are consistent with two transport channels per monomer. J Biol Chem. 2002 Aug 23;277(34):30991-7. doi: 10.1074/jbc.M202763200. Epub 2002 May 24.

Results Reference

background

PubMed Identifier

12420362

Citation

De Vivo DC, Wang D, Pascual JM, Ho YY. Glucose transporter protein syndromes. Int Rev Neurobiol. 2002;51:259-88. doi: 10.1016/s0074-7742(02)51008-4. No abstract available.

Results Reference

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PubMed Identifier

11603379

Citation

Brockmann K, Wang D, Korenke CG, von Moers A, Ho YY, Pascual JM, Kuang K, Yang H, Ma L, Kranz-Eble P, Fischbarg J, Hanefeld F, De Vivo DC. Autosomal dominant glut-1 deficiency syndrome and familial epilepsy. Ann Neurol. 2001 Oct;50(4):476-85. doi: 10.1002/ana.1222.

Results Reference

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PubMed Identifier

22682223

Citation

Marin-Valencia I, Yang C, Mashimo T, Cho S, Baek H, Yang XL, Rajagopalan KN, Maddie M, Vemireddy V, Zhao Z, Cai L, Good L, Tu BP, Hatanpaa KJ, Mickey BE, Mates JM, Pascual JM, Maher EA, Malloy CR, Deberardinis RJ, Bachoo RM. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse human glioblastomas in the mouse brain in vivo. Cell Metab. 2012 Jun 6;15(6):827-37. doi: 10.1016/j.cmet.2012.05.001. Erratum In: Cell Metab. 2012 Nov 7;16(5):686.

Results Reference

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PubMed Identifier

22419606

Citation

Maher EA, Marin-Valencia I, Bachoo RM, Mashimo T, Raisanen J, Hatanpaa KJ, Jindal A, Jeffrey FM, Choi C, Madden C, Mathews D, Pascual JM, Mickey BE, Malloy CR, DeBerardinis RJ. Metabolism of [U-13 C]glucose in human brain tumors in vivo. NMR Biomed. 2012 Nov;25(11):1234-44. doi: 10.1002/nbm.2794. Epub 2012 Mar 15.

Results Reference

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PubMed Identifier

22383401

Citation

Marin-Valencia I, Cho SK, Rakheja D, Hatanpaa KJ, Kapur P, Mashimo T, Jindal A, Vemireddy V, Good LB, Raisanen J, Sun X, Mickey B, Choi C, Takahashi M, Togao O, Pascual JM, Deberardinis RJ, Maher EA, Malloy CR, Bachoo RM. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors. NMR Biomed. 2012 Oct;25(10):1177-86. doi: 10.1002/nbm.2787. Epub 2012 Mar 1.

Results Reference

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PubMed Identifier

22281806

Citation

Choi C, Ganji SK, DeBerardinis RJ, Hatanpaa KJ, Rakheja D, Kovacs Z, Yang XL, Mashimo T, Raisanen JM, Marin-Valencia I, Pascual JM, Madden CJ, Mickey BE, Malloy CR, Bachoo RM, Maher EA. 2-hydroxyglutarate detection by magnetic resonance spectroscopy in IDH-mutated patients with gliomas. Nat Med. 2012 Jan 26;18(4):624-9. doi: 10.1038/nm.2682.

Results Reference

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PubMed Identifier

21394775

Citation

Choi C, Ganji SK, DeBerardinis RJ, Dimitrov IE, Pascual JM, Bachoo R, Mickey BE, Malloy CR, Maher EA. Measurement of glycine in the human brain in vivo by 1H-MRS at 3 T: application in brain tumors. Magn Reson Med. 2011 Sep;66(3):609-18. doi: 10.1002/mrm.22857. Epub 2011 Mar 9.

Results Reference

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Links:

URL

http://www.g1dregistry.org

Description

The G1D Registry

Learn more about this trial

Triheptanoin (C7 Oil), a Food Supplement, for Glucose Transporter Type I Deficiency (G1D)

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