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.

Study Overview

• Status: Recruiting
• Conditions: Pyruvate Dehydrogenase Complex Deficiency
• Intervention / Treatment: Drug: Triheptanoin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Angela Riemenschneider; Phone Number: 412-692-5232; Email: angela.riemenschneider@chp.edu
• Study Contact Backup: Name: Jirair Bedoyan, MD, PhD; Email: bedoyanjk@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Recruiting
      • UPMC Children's Hospital of Pittsburgh
      • Principal Investigator: Jirair Bedoyan, MD, PhD
      • Contact: Jirair Bedoyan, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

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: Triheptanoin; Open label study	Drug: Triheptanoin; Open-label design with doses of triheptanoin up to 4.0 gm/kg triheptanoin; Other Names: Dojolvi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who report side-effects related to gastrointestinal (GI) distress		24 months
Normalization of biochemical markers of disease (lactate)	Change in lactate levels, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in mmol/L	24 months
Normalization of biochemical markers of disease (pyruvate)	Change in pyruvate levels, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in mg/dl	24 months
Normalization of biochemical markers of disease (β-hydroxybutyrate level)	Change in β-hydroxybutyrate levels, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in mmol/L	24 months
Normalization of biochemical markers of disease (Alanine/Leucine ratio)	Change in Alanine/Leucine ratios, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in μmol/L	24 months
Normalization of biochemical markers of disease (Alanine/Lysine ratio)	Change in Alanine/Lysine ratios, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in μmol/L	24 months
Normalization of biochemical markers of disease (Alanine/Proline ratio)	Change in Alanine/Proline ratios, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in μmol/L	24 months
More efficacious seizure control	Measured by a reduction or alteration of home antiepileptics use, from before and after triheptanoin is initiated	24 months
More efficacious metabolic control	Measured by a reduction in episodes of metabolic decompensation, from before and after triheptanoin is initiated	24 months
More efficacious disease control	Measured by a reduction in the frequency of disease related hospitalizations, from before and after triheptanoin is initiated	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improved quality of life	Measured by a change in scores on the PedsQL, from before and after trihepatnoin is initiated	24 months
Improved long-term maintenance and tolerance of diet	Measured by parental report of diet maintenance and tolerance, from before and after triheptanoin is initiated	24 months
Improved quality of life	Measured by a change in scores on the MetabQoL, from before and after trihepatnoin is initiated	24 months

Collaborators and Investigators

• Sponsor: Jirair Krikor Bedoyan
• Collaborators: Ultragenyx Pharmaceutical Inc
• Investigators: Principal Investigator: Jirair Bedoyan, MD, PhD, UPMC Children's Hospital of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: March 22, 2024
• First Submitted That Met QC Criteria: March 29, 2024
• First Posted (Actual): April 1, 2024

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 12, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Pyruvate Dehydrogenase Complex Deficiency
• Additional Relevant MeSH Terms: Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Neurobehavioral Manifestations; Heredodegenerative Disorders, Nervous System; Intellectual Disability; Genetic Diseases, X-Linked; Carbohydrate Metabolism, Inborn Errors; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Pyruvate Metabolism, Inborn Errors; Mitochondrial Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; X-Linked Intellectual Disability; Pyruvate Dehydrogenase Complex Deficiency Disease; triheptanoin
• Other Study ID Numbers: STUDY23050042; UX007-IST236 (Other Grant/Funding Number: Ultragenyx Pharmaceutical Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No