Clinical trial NCT01461304: Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism
Official title: Dietary Therapy for Inherited Disorders of Energy Metabolism
Study type: EXPANDED_ACCESS
Overall status: NO_LONGER_AVAILABLE
Conditions: Very Long-chain acylCoA Dehydrogenase (VLCAD) Deficiency
Carnitine Palmitoyltransferase Deficiencies (CPT1, CPT2)
Mitochondrial Trifunctional Protein Deficiency
Long-chain Hydroxyacyl-CoA Dehydrogenase Deficiency
Glycogen Storage Disorders
Pyruvate Carboxylase Deficiency Disease
ACYL-CoA DEHYDROGENASE FAMILY, MEMBER 9, DEFICIENCY of
Barth Syndrome
Keywords: fatty acid oxidation
triheptanoin
long-chain fatty acid oxidation disorders
LCHADD
VLCADD
CPT1
CPT2
TFP
Glycogen Storage Disorders
GSD
Pyruvate Carboxylase
PC
ACAD9
Barth
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Ultragenyx Pharmaceutical Inc
First posted: 2011-10-28
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: This is a compassionate use study to allow patients already taking triheptanoin (C7) through previous studies to continue to receive the supplement. It will also allow triheptanoin supplementation in patients with qualifying disorders if they are failing conventional therapy.

Detailed description: This study will treat children and adults who have documented deficiencies of mitochondrial fatty acid oxidation including disorders of the following enzymes: Carnitine-Acylcarnitine Translocase (CATR), Carnitine Palmitoyltransferase I and II (CPT I, CPT II), Very-Long Chain Acyl-CoA dehydrogenase (VLCAD), L-3-Hydroxy-Acyl-CoA Dehydrogenase (LCHAD), Acyl-CoA Dehydrogenase type 9 (ACAD9) and Mitochondrial Trifunctional Protein (TFP) with triheptanoin oil. This study is also open to patients with any type of glycogen storage disease, pyruvate carboxylase deficiency, or Barth Syndrome.

Symptoms often persist with standard diet including supplementation with medium chain triglyceride oil. Preliminary data shows triheptanoin to reverse many of the clinical symptoms not well controlled by standard diet.

On study entry, clinical and laboratory assessments will be carried out with the subject on their usual home diet. A complete history and physical exam will be performed. An echocardiogram must be obtained within the past year or it will be performed on the day of study entry. Following analysis of their diet and a negative pregnancy test, subjects will receive a modified diet containing triheptanoin (up to 2 grams/kg/24 hours for most subjects; subjects who experience cardiomyopathy may receive doses up to 4 grams/kg/24 hours), or continued on their previously established triheptanoin dose; not to exceed RDA for fat, substituted for their MCT oil and/or natural fat. This will be given by g-tube or orally divided into 2 or more doses. The dose will be adjusted on the basis of safety laboratory monitoring at specific time points and for adverse symptoms. The remainder of their diet will be modified to maintain appropriate caloric intake and balance. Total calories appropriate for RDA will be prescribed.

Study subjects will continue the triheptanoin-supplemented diet for a period of 12 months and then be able to continue into an indefinite extension phase in this compassionate use study. Laboratory evaluations will take place at two, six, and twelve months, as well as every 12 months in the extension phase. Laboratory tests may be completed at a local lab and the results forwarded to the PI for review between visits in Pittsburgh. Patients will monitor their weight at home on a monthly basis. Interim metabolic evaluations will be arranged as needed on a clinical basis with the study PI or the subject's home metabolic physician. Following the initial 12 months of the protocol, subjects will be placed on a continuing schedule for maintenance of triheptanoin therapy with a yearly follow up visit for an undeterminable period of time. Echocardiograms must be completed on an annual basis and sent to the study PI to review.

Travel to Pittsburgh, PA at the start of the study and annually is the responsibility of the subjects. Additionally, there may be study costs that insurance will not cover and subjects will be responsible for covering them. Examples of out-of-pocket study costs subjects may incur in addition to travel expenses including the following: necessary laboratory testing and echocardiograms. The study medication will be provided free of charge.

Eligibility criteria: Inclusion Criteria:

* Ages 1 month and up
* Diagnosis of disorder in long chain fatty acid oxidation, glycogen storage disease, pyruvate carboxylase deficiency, or Barth Syndrome
* Currently receiving triheptanoin as result of participation in previous study will be eligible if they have one of the included diagnoses
* Prefer 2 of following 3: acylcarnitine profile, fibroblast acylcarnitine profile or positive medical genetic test

Exclusion Criteria:

* Pregnant females
* MCAD deficiency
* disorder of short and medium chain fatty acid oxidation or ketone body metabolism

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Division of Medical Genetics, Children's Hospital of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Pittsburgh, University of Pittsburgh
name: Jerry Vockley, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: