Phase II Open Label Study Using Triheptanoin in Patients With Glucose Type 1 Transporter Deficiency GLUT1-DS (GLUT-HEP)

The purpose of this project is to study the efficacy of triheptanoin oil in patients with GLUT1 deficiency syndrome.

Study Overview

• Status: Completed
• Conditions: Glut1 Deficiency Syndrome
• Intervention / Treatment: Drug: GLUT1 DS

Detailed Description

The primary objective of the study is:

- to evaluate the capacity of triheptanoïn to improve the condition of patients with GLUT1-DS

The secondary objectives of the study are:

• to confirm the short-term safety of triheptanoïn therapy in patients with GLUT1-DS
• to evaluate the short-term effects of triheptanoïn treatment on motor function, autonomy, quality of life and clinical signs of patients with GLUT1-DS
• to evaluate the effect of triheptanoïn on brain energy metabolism using non-invasive 31P-MRS spectroscopy after activation of the occipital cortex in order to measure the levels of high-energy phosphates (such as ATP and phosphocreatine)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75013
    • Brain and Spine Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Mutation in SLC2A1 gene
• Age > 3 years
• Patient with history/frequency of seizures or movement disorders documented at least 3 months prior to the beginning of the study
• Covered by french social security
• Patients who freely agree to participate in this study and understand the nature, risks and benefits of this study and give their written informed consent. (In addition to the requirement for the consent of parents or the legal representative, adolescents can provide additional informed consent to participate in clinical trials)

Exclusion Criteria:

• Evidence of psychiatric disorder
• Attendant neurological disorder
• Comorbid medical condition that would render them unsuitable for the study, e.g. HIV, diabetes
• Pregnant or parturient or lactating women
• Unwillingness to be informed in case of abnormal MRI
• Failure to give written informed consent
• Unable to understand the protocol
• Unable to participate to the whole study
• Absence of signed informed consent
• Persons deprived of their liberty by judicial or administrative decision
• Person subject to an exclusion period for another research
• Subjects with exclusion criteria required by french law

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLUT1 DS	Drug: GLUT1 DS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of paroxystic events	The number of paroxystic events, in particular abnormal movements, will be collected during trihepatnoin treatment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety	Should the whole blood levels of propionylcarnitine increase above 8 μmol/l, the dose of triheptanoin will be reduced until the decrease of whole blood propionylcarnitine is below 8 μmol/l. Should an organic acid abnormality such as an excessive urinary excretion of propionate metabolites such as 3-hydroxypropionic, 2-methylcitric, propionylglycine, tiglylglycine and/or methylmalonic acid occur, the dose of triheptanoin will be reduced until normalization of the organic acid and acylcarnitine profile. If still abnormal, patient will be excluded from the study. For GI distress, the research dietitian will instruct the patient regarding taking the dose over a longer period of time (30 minutes). If GI distress persists, triheptanoin dose will be reduced by 50% and re-increased progressively as the problems resolve with the patients working closely with research dietitian until tolerance of the full dose is achieved.	6 months
6 minutes walk test		6 months
9 hole Peg board		6 months
Clinical Global Impression Scales		6 months
Schwab-England scale		6 months
Vineland Scale		6 months
Fatigue Severity Scale		6 months
Fatigue Visual Scale		6 months
Brain 31phosphorus magnetic resonance spectroscopy	Ratio of Inorganic Phosphate (Pi) over Phosphocreatine during visual stimulation	6 months

Collaborators and Investigators

• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France
• Collaborators: Ultragenyx Pharmaceutical Inc
• Investigators: Principal Investigator: Fanny Mochel, MD, PhD, Institut National de la Santé Et de la Recherche Médicale, France

Publications and helpful links

General Publications

• Mochel F, Hainque E, Gras D, Adanyeguh IM, Caillet S, Heron B, Roubertie A, Kaphan E, Valabregue R, Rinaldi D, Vuillaumier S, Schiffmann R, Ottolenghi C, Hogrel JY, Servais L, Roze E. Triheptanoin dramatically reduces paroxysmal motor disorder in patients with GLUT1 deficiency. J Neurol Neurosurg Psychiatry. 2016 May;87(5):550-3. doi: 10.1136/jnnp-2015-311475. Epub 2015 Nov 3.
• Hainque E, Meneret A, Gras D, Atencio M, Luton MP, Barbier M, De Saint Martin A, Billette de Villemeur T, Ottolenghi C, Roze E, Mochel F. Transition from ketogenic diet to triheptanoin in patients with GLUT1 deficiency syndrome. J Neurol Neurosurg Psychiatry. 2020 Apr;91(4):444-445. doi: 10.1136/jnnp-2019-321694. Epub 2019 Nov 6. No abstract available.
• Hainque E, Gras D, Meneret A, Atencio M, Luton MP, Barbier M, Doulazmi M, Habarou F, Ottolenghi C, Roze E, Mochel F. Long-term follow-up in an open-label trial of triheptanoin in GLUT1 deficiency syndrome: a sustained dramatic effect. J Neurol Neurosurg Psychiatry. 2019 Nov;90(11):1291-1293. doi: 10.1136/jnnp-2018-320283. Epub 2019 Apr 4. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2013
• Primary Completion (Actual): July 4, 2019
• Study Completion (Actual): July 4, 2019

Study Registration Dates

• First Submitted: December 3, 2013
• First Submitted That Met QC Criteria: December 12, 2013
• First Posted (Estimated): December 18, 2013

Study Record Updates

• Last Update Posted (Estimated): October 3, 2025
• Last Update Submitted That Met QC Criteria: September 29, 2025
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glut1 Deficiency Syndrome
• Other Study ID Numbers: C13-37; 2013-A01300-45 (Registry Identifier: IDRCB)