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
Intervention: Triheptanoin
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 1 Year
Maximum age: 50 Years
Healthy volunteers: No
Keywords: Triheptanoin; Glut1 DS; Epilepsy; Seizures

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.
    

Eligibility criteria:

        Inclusion Criteria:

        Individuals eligible to participate in this study must meet all of the following criteria:

          1. Patients with GLUT1 DS by physician diagnosis

          2. Males and females, aged 1 to 50 years

          3. Allowed to be on concomitant AEDs

          4. Patients are able to tolerate triheptanoin if they have been (or are currently being)
             treated with this medication

          5. Must, in the opinion of the investigator, be willing and able to comply with study
             procedures and schedule

          6. Provide written assent (if appropriate) and written informed consent by a Legally
             Authorized Representative (LAR) after the nature of the study has been explained, and
             prior to any research-related procedures

          7. Sexually active subjects must be willing to use an acceptable method of contraception
             while participating in the study

          8. Females of childbearing potential must have a negative pregnancy test at Screening and
             be willing to have additional pregnancy tests during the study

        Exclusion Criteria:

        Individuals who meet any of the following exclusion criteria will not be eligible to
        participate in the study:

          1. Patients and their Legally Authorized Representatives (as appropriate) not willing or
             able to give written or verbal assent or written informed consent.

          2. Concomitant administration of a ketogenic diet for the treatment of GLUT1 deficiency

          3. Concomitant administration of valproic acid

          4. In the Investigator's opinion, the patient may not be compliant

          5. Pregnant or breastfeeding an infant at screening

          6. Has a concurrent disease or condition, or laboratory abnormality that, in the view of
             the Investigator, places the subject at high risk for adverse events, or introduces
             additional safety concerns

          7. History of or current suicidal ideation, behavior and attempts

          8. Patient qualifies for any other clinical trial designed to progressively evaluate the
             safety and efficacy of triheptanoin as approved by the FDA under a separate IND which
             is open at Cook Children's