An Open-Label Trial of Triheptanoin in Patients With Glucose Transporter Type-1 Deficiency Syndrome
Condition: Glucose Transporter Type-1 Deficiency Syndrome (Glut1 DS)
MeSH terms: Carbohydrate Metabolism, Inborn Errors; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      This study is being done to assess the safety and long-term efficacy of triheptanoin in
      pediatric patients with Glut1 DS over a 5-year treatment period. Glut 1 is a protein that
      helps transport glucose to the brain. Glucose is the brain's primary source of energy. Glut 1
      DS prevents this protein from being effectively produced, causing deprivation of energy to
      the neurons of the of the brain.

      Glut1 DS is a severely debilitating disease characterized by seizures, developmental delay
      and movement disorder. There are currently no approved treatments specific to Glut1 DS.
      Treatment generally includes medications for control of seizures. The use of a ketogenic diet
      can be effective in controlling seizures when medications are ineffective or provide
      insufficient control. However, the ketogenic diet may be very difficult for patients to
      maintain for long periods of time, and there may be negative secondary long-term effects of
      ketogenic diet.. Triheptanoin is metabolized to molecules that can provide an alternative
      energy source to the brain, and appears to help in controlling seizures without many of the
      difficulties of the ketogenic diet.

      Eligible patients may be those who have been diagnosed with GLUT1 DS, and have discontinued
      or are not currently on ketogenic diet, or are able to tolerate triheptanoin if they have
      been treated or are currently being treated with triheptanoin and do not qualify for any
      other clinical trial.
    

Detailed description: 
      Triheptanoin is proposed for the treatment of seizures in glucose transporter type-1
      deficiency syndrome (Glut1 DS). Glut1 DS is a rare disease with an estimated US prevalence of
      ~3,300.

      The proposed study is an open-label study to assess the safety and long-term efficacy of
      triheptanoin in patients with Glut1 DS over a 5-year treatment period. Eligible patients may
      be those who are able to tolerate triheptanoin if they have been treated or are currently
      being treated with triheptanoin and do not qualify for any other clinical trial. Subjects
      previously treated with triheptanoin will continue to dose at approximately 35% of total
      daily calories (~1-4g/kg/day, depending on age). Subjects who are naïve to triheptanoin will
      begin a 2-week fixed titration schedule up until they have reached 35% of total daily
      calories.

      The primary objective of the study is to evaluate the safety of triheptanoin via adverse
      event rates and laboratory values. The secondary objective is to evaluate the long-term
      efficacy of triheptanoin as measured by the change in seizure frequency from historical
      baseline.
    

Intervention name(s): Triheptanoin
Intervention type(s): Drug
Intervention description(s): Schedule A: Subjects previously treated with triheptanoin will continue to dose at approximately 35% of total daily calories (~1-4g/kg/day, depending on age).
Schedule B: Subjects who are naïve to triheptanoin will begin a 2-week fixed titration schedule up until they have reached 35% of total daily calories (~1-4 g/kg/day depending on age). If a subject has not reached the target of 35% of total daily calories, by the end of the 2-week fixed titration period, dose titration should continue until achieved or until the maximally tolerated dose has been established.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Triheptanoin; Glut1 DS; Epilepsy; Seizures