Treatment Development for Glucose Transporter Type I Deficiency Syndrome (G1D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02018315

Recruitment Status : Completed

First Posted : December 23, 2013

Results First Posted : October 31, 2019

Last Update Posted : October 31, 2019

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Juan Pascual, University of Texas Southwestern Medical Center

Study Description

Brief 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 promising by supplying anaplerotic precursors through metabolism of odd-carbon fatty acids that can enter the citric acid cycle (CAC) through alternative metabolic pathways.

Condition or disease	Intervention/treatment	Phase
Glucose Transporter Type 1 Deficiency Syndrome GLUT1 Deficiency Syndrome	Drug: Triheptanoin	Phase 1

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

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	14 participants
Allocation:	N/A
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
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)
Study Start Date :	January 2012
Actual Primary Completion Date :	January 2013
Actual Study Completion Date :	March 2014

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: GLUT1 deficiency syndrome

Drug Information available for: Triheptanoin

Genetic and Rare Diseases Information Center resources: Glucose Transporter Type 1 Deficiency Syndrome

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Triheptanoin 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.	Drug: Triheptanoin Triheptanoin is a 7-carbon medium chain triglyceride Other Names: C7 Heptanoate

Outcome Measures

Primary Outcome Measures :

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.

Secondary Outcome Measures :

Number of Participants With Change in Brain Metabolic Rate After 3 Months [ Time Frame: 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.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	1 Month to 20 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02018315

Locations

Layout table for location information

United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390

Sponsors and Collaborators

Juan Pascual

Investigators

Layout table for investigator information

Principal Investigator:	Juan M. Pascual, MD, PhD	UT Southwestern Medical Center

More Information

Additional Information:

The G1D Registry This link exits the ClinicalTrials.gov site

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.

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.

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.

Wang D, Pascual JM, De Vivo D. Glucose Transporter Type 1 Deficiency Syndrome. 2002 Jul 30 [updated 2018 Mar 1]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from http://www.ncbi.nlm.nih.gov/books/NBK1430/

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

Layout table for additonal information

Responsible Party:	Juan Pascual, Associate Professor, Director of the Rare Brain Disorders Program, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT02018315
Other Study ID Numbers:	UTSW 122010-186
First Posted:	December 23, 2013 Key Record Dates
Results First Posted:	October 31, 2019
Last Update Posted:	October 31, 2019
Last Verified:	October 2019

Keywords provided by Juan Pascual, University of Texas Southwestern Medical Center:


G1D Glut1 Disorder Glucose Transporter Type 1 Disorder Glucose Transporter Type I Disorder

Additional relevant MeSH terms:

Layout table for MeSH terms

Syndrome Disease Pathologic Processes

To Top