Nutritional Therapy of the Deficits of Oxidation Mitochondrial of the Fatty Acids

This study has been completed.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT00328159
First received: May 18, 2006
Last updated: February 16, 2011
Last verified: March 2007
  Purpose

Usual dietary therapies of mitochondrial fatty acid oxidation disorders (FAO) are based on 3 strategies:

  • limitation of lipid intake in the diet;
  • supplementation of the diet with medium-chain triglycerides (MCT) for patients affected with disorders of long-chain FAO;
  • some specific supplementations (for example, L-carnitine).

These strategies are often ineffective. The aim of the present study is to evaluate new therapeutic ways based on the underlying energetic defect observed in these disorders. The long-term goal is to develop efficient therapies of these disorders.


Condition Intervention
Inborn Errors of Metabolism
Drug: Oil special 107 and MYGLIOL 810

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Dietary Therapy of Mitochondrial Fatty Acids Oxidation. A Clinical Study of Treatment With Odd Carbons Medium-chain Fatty Acids

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Strength tests [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Biological parameters (acylcarnitines profile, modifications of urinary organic acids) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Clinical parameters (echocardiography) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Ergometric testing [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Hepatic functions [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Hypoglycaemia [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Rhabdomyolyses [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Enrollment: 20
Study Start Date: June 2006
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Detailed Description:

The main specific aim of this study will be to determine the efficiency of odd-chain MCT: TRIHEPTANOIN (Tri-C7) and its metabolites, BETA-HYDROXYPENTANOATE (BHP) and BETA-KETOPENTANOATE (BKP), as potential treatments by orale or enteral routes. These compounds are efficiently used for energy production, despite long-chain FAO enzyme defects. They use alternative metabolic pathways and have anaplerotic effects due to propionyl-CoA production by the thiolytic cleavage of odd carbon ketone bodies.

The efficiency of these compounds will be compared with conventional diet (MCT) for each patient. Because of frequent phenotypic variations observed for each of these diseases, each patient will be his own control.

The same protocol study will be followed in 2 centers: Dallas, USA (main investigator: Dr CR Roe) and Paris, France (main investigator: Dr G TOUATI). It is planned to include 80 patients (60 in Dallas, 20 in Paris), during the next 2 years. The patients will be affected with 6 proven defects that are specific defects of long-chain FAO: carnitine palmitoyltransferase 1 (CPT1), carnitine-acylcarnitine translocase (CAT), carnitine palmitoyltransferase 2 (CPT2), very-long chain acyl-CoA dehydrogenase (VLCAD), L-3-hydroxy-acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (MTP).

The used methodology will be a control randomized study to compare the efficiency of 2 diet therapies: TRIHEPTANOIN versus conventional MCT. The studied parameters will depend on each disease and will depend on the affected organs in each patient. Main studied clinical parameters will be: survival rate, number of metabolic acute decompensation, frequency and severity of hypoglycemias, frequency and severity of rhabdomyolyses, evolution of cardiac or hepatic manifestations, muscular strength, and quality of life. Main studied biological parameters will be: TRIHEPTANOIN use during meal tests, modifications of plasma acylcarnitines profile, modifications of urinary organic acids, blood measurements of CPK and transaminases. Cardiac echographies will be performed for the follow-up of cardiomyopathies, ergometric testing and strength tests will be performed for disorders that affect muscular function.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient with an enzyme deficiency of carnitine palmitoyltransferase 1 (CPT1), carnitine-acylcarnitine translocase (CAT), carnitine palmitoyltransferase 2 (CPT2), very-long chain acyl-CoA dehydrogenase (VLCAD), L-3-hydroxy-acyl-CoA dehydrogenase (LCHAD) or trifunctional protein (MTP).
  • Covered by health and social insurance
  • Written informed consent

Exclusion Criteria:

  • Patient affected with FAO dysfunction secondary to other cause (e.g. mitochondrial respiratory chain disorders)
  • Patient with suspected FAO disorder that has not been proven (by enzymatic or molecular test)
  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: NCT00328159

Locations
France
Necker University Hospital - Metabolism Unit
Paris, France, 75743
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Guy Touati, PU-PH Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Marie CASTERA, Department of Clinical Research of developpement
ClinicalTrials.gov Identifier: NCT00328159     History of Changes
Other Study ID Numbers: P030435
Study First Received: May 18, 2006
Last Updated: February 16, 2011
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
FAO disorders
long-chain FAO enzyme defects
inborn errors of metabolism
carnitine palmitoyltransferase 1 (CPT1),
carnitine-acylcarnitine translocase (CAT),
carnitine palmitoyltransferase 2 (CPT2),
very-long chain acyl-CoA dehydrogenase (VLCAD),
L-3-hydroxy-acyl-CoA dehydrogenase (LCHAD)
or trifunctional protein (MTP).

Additional relevant MeSH terms:
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on July 28, 2014