Triheptanoin for Children With Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency

An Open Label, Exploratory, Proof-of Concept Study of Triheptanoin as Treatment for Patients With Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency

This is a medical research study to test a medication in patients with a disease called Pyruvate Dehydrogenase Complex (PDC) Deficiency. The medication is triheptanoin, which is currently FDA approved for the treatment of Long-Chain Fatty Acid Oxidation Disorders. Previous research suggests that triheptanoin may also be effective in the treatment PDC Deficiency. This study will investigate the safety and efficacy (how well it works) of triheptanoin in patients with PDC Deficiency.

Participation in the study will require the patient to participate in up to 10 visits over a two-year period. Five of those visits must be done at the UPMC Children's Hospital of Pittsburgh (CHP). Other visits can take place at CHP or remotely. All of these visits will include blood draws.

Triheptanoin will be added to the patients' diet and administered at least 4 times per day. The target dose will be 1.2-3.9 g of triheptanoin per kg body weight with a max goal dose of about 4 g/kg per day.

The triheptanoin will be provided to the patients at no cost. All other costs will be billed to the patients' insurance.

Inclusion Criteria:

1. Age 1 year to <18 years of age
2. Subjects with PDCD would need to have a metabolic physician following their clinical care needs prior to their enrollment in the study
3. Diagnosis of PDCD by molecular genetic confirmation of PDHA1, PDHB, DLAT, PDHX, or PDP1 mutation
4. Not pregnant or lactating
5. Parental permission and assent of minor and willingness to comply with study procedures
6. Not participating in any interventional treatment clinical trials
7. Not a recipient of gene therapy, organ transplant, or bone-marrow transplantation
8. If currently on any investigational drugs or therapies, must complete a 30-day washout period prior to Intake & Dosing (Day 1).
9. Negative pregnancy test for all female patients of childbearing age. Individuals of childbearing potential must agree to use a highly effective method of contraception, and males must agree not to father a child or donate sperm. True abstinence for the duration of the study will also be accepted.
10. Subjects are following some form or type of ketogenic diet at the time of the screening visit.

Exclusion Criteria:

1. Diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD)
2. Use of alcohol or drugs of abuse
3. Evidence of liver disease as defined by elevations of AST or ALT >2x ULN in the past 6 months
4. Pregnant, breastfeeding, or lactating females
5. On any investigational product research study (and not completed the required 30-day washout period prior to Intake & Dosing) or recipient of gene therapy or organ or bone-marrow transplantation