Compassionate Use of Triheptanoin (C7) for Fatty Acid Oxidation Disorders and Glycogen Storage Disease

Expanded access is currently available for this treatment.
Verified October 2013 by University of Pittsburgh
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01461304
First received: October 25, 2011
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention
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, Type B
Acyl-coA Dehydrogenase, Type 9
Drug: triheptanoin

Study Type: Expanded Access     What is Expanded Access?
Official Title: Dietary Therapy for Inherited Disorders of Mitochondrial Fatty Acid Oxidation and Glycogenosis

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Study Start Date: December 2009
Estimated Primary Completion Date: November 2019 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: triheptanoin
    subjects will receive a modified diet containing triheptanoin (up to 2 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. 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.
    Other Name: C7
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 or pyruvate carboxylase deficiency, type B.

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), 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: clinic visits, necessary laboratory testing, and echocardiograms. The study medication will be provided free of charge.

  Eligibility

Ages Eligible for Study:   1 Month and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages 1 month and up
  • Diagnosis of disorder in long chain fatty acid oxidation, glycogen storage disease, or pyruvate carboxylase deficiency, type B
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01461304

Contacts
Contact: Elizabeth McCracken, MS, CGC 412-692-5662

Locations
United States, Pennsylvania
University of Pittsburgh Division of Medical Genetics, Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
Contact: Elizabeth McCracken, MS, CGC       elizabeth.mccracken@chp.edu   
Sponsors and Collaborators
University of Pittsburgh
Ultragenyx Pharmaceutical Inc
Investigators
Principal Investigator: Jerry Vockley, MD, PhD Children's Hospital of Pittsburgh, University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01461304     History of Changes
Other Study ID Numbers: PRO08020019
Study First Received: October 25, 2011
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
fatty acid oxidation
triheptanoin
long-chain fatty acid oxidation disorders
LCHADD
VLCADD
CPT1
CPT2
TFP
Glycogen Storage Disorders
GSD
Pyruvate Carboxylase
PC
ACAD9

Additional relevant MeSH terms:
Glycogen Storage Disease
Protein Deficiency
Pyruvate Carboxylase Deficiency Disease
Lipid Metabolism, Inborn Errors
Cardiomyopathies
Rhabdomyolysis
Mitochondrial Myopathies
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Deficiency Diseases
Malnutrition
Nutrition Disorders
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Pyruvate Metabolism, Inborn Errors
Mitochondrial Diseases
Lipid Metabolism Disorders
Heart Diseases
Cardiovascular Diseases
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on August 01, 2014