NCT02018315

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
14

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jan 2012

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2012

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2013

Completed
11 months until next milestone

First Submitted

Initial submission to the registry

December 11, 2013

Completed
12 days until next milestone

First Posted

Study publicly available on registry

December 23, 2013

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2014

Completed
5.7 years until next milestone

Results Posted

Study results publicly available

October 31, 2019

Completed
Last Updated

October 31, 2019

Status Verified

October 1, 2019

Enrollment Period

1 year

First QC Date

December 11, 2013

Results QC Date

February 12, 2019

Last Update Submit

October 8, 2019

Conditions

Glucose Transporter Type 1 Deficiency SyndromeGLUT1 Deficiency Syndrome

Keywords

G1DGlut1 DisorderGlucose Transporter Type 1 DisorderGlucose Transporter Type I Disorder

Outcome Measures

Primary Outcomes (1)

  • 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.

    1 day

Secondary Outcomes (1)

  • Number of Participants With Change in Brain Metabolic Rate After 3 Months

    3 months

Study Arms (1)

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.

Drug: Triheptanoin

Interventions

TriheptanoinDRUG

Triheptanoin is a 7-carbon medium chain triglyceride

Also known as: C7, Heptanoate
Triheptanoin

Eligibility Criteria

Age1 Month - 20 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (18)

  • 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.

    PMID: 23072752BACKGROUND

  • 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.

    PMID: 22683290BACKGROUND

  • 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.

    PMID: 20598931BACKGROUND

  • Wang 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, Pagon RA, 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/

    PMID: 20301603BACKGROUND

  • 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.

    PMID: 19901175BACKGROUND

  • 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.

    PMID: 19225367BACKGROUND

  • 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.

    PMID: 17296829BACKGROUND

  • 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.

    PMID: 15132717BACKGROUND

  • 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.

    PMID: 18387950BACKGROUND

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

    PMID: 17169300BACKGROUND

  • 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.

    PMID: 16497725BACKGROUND

  • 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.

    PMID: 15622525BACKGROUND

  • 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.

    PMID: 15152356BACKGROUND

  • 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.

    PMID: 13129919BACKGROUND

  • 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.

    PMID: 12325075BACKGROUND

  • 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.

    PMID: 12032147BACKGROUND

  • 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.

    PMID: 12420362BACKGROUND

  • 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.

    PMID: 11603379BACKGROUND

MeSH Terms

Conditions

Glut1 Deficiency Syndrome

Interventions

triheptanoin

Results Point of Contact

Title
Juan Pascual, M.D., Ph.D.
Organization
University of Texas Southwestern Medical Center
juan.pascual@utsouthwestern.edu
214-648-3550

Study Officials

  • Juan M. Pascual, MD, PhD

    University of Texas Southwestern Medical Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor, Director of the Rare Brain Disorders Program

Study Record Dates

First Submitted

December 11, 2013

First Posted

December 23, 2013

Study Start

January 1, 2012

Primary Completion

January 1, 2013

Study Completion

March 1, 2014

Last Updated

October 31, 2019

Results First Posted

October 31, 2019

Record last verified: 2019-10

Locations

US(1)