Pilot Study of Triheptanoin in Patients With Glucose Transporter 1 Deficiency Syndrome

NCT02000960 | Unknown Phase 2 DMC

• 2 other identifiers: H13-03330VGTPH001
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Glucose transporter deficiency syndrome (Glut1-DS) is a form of pediatric epilepsy caused by a genetic mutation that disrupts the body's ability to process food from the child's diet into sugar (energy) needed to support brain function. Children with Glut1-DS experience seizures that are not controlled by anticonvulsant medications, as well as delays in cognitive and motor development. Currently, Glut1-DS is treated with the ketogenic diet, a high-fat, low-sugar diet that provides the brain with an alternate source of energy. Despite the significant improvement of seizures upon this diet, seizure control is incomplete in a majority of children, and they continue to experience problems with brain development. Our team of researchers and clinicians with expertise in metabolic diseases, neurology, pediatrics, biochemistry, and genetics believes that there is an opportunity to achieve CURE's goal of "No Seizures/No Side Effects" for children with Glut1-DS by investigating the use of a new treatment option that is designed to compensate for the underlying biochemical deficiency thought to contribute both to the seizures and to the impaired brain development associated with Glut1-DS. The proposed treatment involves incorporating a special type of oil, called triheptanoin, into the ketogenic diet as a way to make up for a specific biochemical deficit affecting kids with Glut1-DS that the standard ketogenic diet fails to address. Our goal is to do a pilot study to test the safety and effectiveness of this promising new treatment option in a small group of children with Glut1-DS.

Conditions

Glucose Transporter Type 1 Deficiency Syndrome

Keywords

Glut1 DS

Outcome Measures

Primary Outcomes (1)

• Seizure Control

  Complete seizure control (measured using seizure log book completed by the parents; defined by absence of clinical seizures and normalization of the EEG)

  8 months

Secondary Outcomes (3)

• Biochemical markers

  8 months

• Neurodevelopmental function

  8 months

• Movement Disorder

  8 months

Other Outcomes (3)

• Seizure Frequency

  8 months

• Clinical Global Impression-Improvement Scale

  8 months

• Patient specific outcomes of interest

  8 months

Study Arms (1)

Triheptanoin

EXPERIMENTAL

All subjects will receive the study treatment which includes adding triheptanoin to the ketogenic diet with a goal intake of 35% total calories provided by triheptanoin (max 100 ml oil/day.

Drug: Triheptanoin

Interventions

Triheptanoin DRUG

Triheptanoin (C7 oil) is a triglyceride of the anaplerotic odd-chain fatty acid heptonate.

Also known as: C7 oil

Triheptanoin

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Confirmed diagnosis of Glut1-DS with mutation(s) in SLC2A1 gene.
• Male or female age 1-18 years.
• Glut1-DS is currently managed with ketogenic diet for a minimum of 4 months prior to baseline visit and patient is willing to maintain this diet for the study duration..
• Inadequate response to ketogenic diet defined by clinical 'breakthrough seizures', confirmed by EEG and at least 1 clinical seizure episode documented in the seizure logbook during the baseline period.
• For participants taking anticonvulsants for their seizures, anti-seizure medication should not be changed at least 4 weeks prior to starting triheptanoin treatment and the participant is willing to maintain the same dosing of all medication(s) during study participation.
• Willing and able to provide written informed consent by parent(s) or guardian(s) or assent by the participant, depending on the age, after the nature of the study has been explained, and prior to any research related-procedures.

You may not qualify if:

• Participants with medium chain acyl-CoA dehydrogenase (MCAD) and propionyl CoA carboxylase (PCC) deficiency will be excluded from the study as MCAD and PCC are required for triheptanoin metabolism.
• A known allergy or sensitivity to any component of triheptanoin.
• The participant is using valproate for controlling his/her seizures. They are eligible for the study, if they had not taken valproate within 3 weeks prior to baseline visit and willing to not take it for the entire study duration. Valproate is an AED that partially inhibits the TCA cycle via alpha-ketoglutarate dehydrogenase, and should not be administered to subjects taking triheptanoin.
• Participant has any condition or situation which, in the investigator's opinion, places the patient at significant risk of adverse events, or may interfere significantly with their participation and compliance in the study.

Sponsors & Collaborators

• University of British Columbia: lead
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

BC Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

MeSH Terms

Conditions

Glut1 Deficiency Syndrome

Interventions

triheptanoin

Study Officials

• Sylvia Stockler

  The University of British Columbia/BC Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2013
• First Posted: December 4, 2013
• Study Start: April 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: October 1, 2016
• Last Updated: June 1, 2016

Record last verified: 2016-05

Locations

CA (1)