Title: Phase 2 Triheptanoin for Tx of Long-Chain Fatty Acid Oxidation Disorder Abstract: Fatty acid oxidation disorders are a family of rare inherited diseases affecting an estimated 1:9000 infants. The recent addition of the fatty acid oxidation disorders to the expanded newborn screening panel in the United States has led to the early diagnosis and treatment of this group of disorders. Presymptomatic treatment through newborn screening has decreased episodes of metabolic decompensation and nearly eliminated mortality. However, patients with a long-chain fatty acid oxidation disorders experience long-term complications such as recurrent rabdomyolysis with or without cardiomyopathy. The prevalence of this sub-group of patients with long-chain fatty acid oxidation is unknown but it is estimated to affect approximately 1000 individuals or less in the United States. Novel treatments for these diseases have lagged behind our diagnostic capabilities. We propose to test a novel treatment hypothesized to increase citric acid cycle intermediates and maximize energy production. This randomized clinical trial will examine the efficacy of triheptanoin supplementation (a heptanoate triglyceride) to treat humans with long-chain FAO disorders. Subjects with a long-chain fatty acid oxidation disorder will be randomly assigned to one of two groups: medium chain triglyceride (MCT) supplementation, the current standard of care, or triheptanoin supplementation for four months. After 4 months we will test the effects of supplement treatment on total energy expenditure, the response to a moderate intensity treadmill exercise test, cardiac function and long-chain fatty acid oxidation capacity. The goal of the project is to determine if triheptanoin therapy has a therapeutic advantage over conventional treatment for long-chain fatty acid oxidation disorders.

Public Health Relevance

Expanded newborn screening has increased our ability to diagnose and begin early treatment of infants with inherited defects in the ability to use fatty acids for energy. However, our treatments have lagged behind our ability to diagnose these diseases. This project will investigate a new therapy for children with fatty acid oxidation disorders: oral supplementation with triheptanoin, a special odd-chain fatty acid.

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project (R01)
Project #
5R01FD003895-03
Application #
8466310
Study Section
Special Emphasis Panel (ZFD1-OPD-N (01))
Project Start
2011-05-20
Project End
2014-04-30
Budget Start
2013-05-01
Budget End
2014-04-30
Support Year
3
Fiscal Year
2013
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Genetics
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239