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

Dietary Therapy of Mitochondrial Fatty Acids Oxidation. A Clinical Study of Treatment With Odd Carbons Medium-chain Fatty Acids

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.

Study Overview

• Status: Completed
• Conditions: Inborn Errors of Metabolism
• Intervention / Treatment: Drug: Oil special 107 and MYGLIOL 810

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75743
    • Necker University Hospital - Metabolism Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Strength tests	24 months
Biological parameters (acylcarnitines profile, modifications of urinary organic acids)	24 months
Clinical parameters (echocardiography)	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Ergometric testing	24 months
Hepatic functions	24 months
Hypoglycaemia	24 months
Rhabdomyolyses	24 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Guy Touati, PU-PH, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (ACTUAL): June 1, 2010
• Study Completion (ACTUAL): June 1, 2010

Study Registration Dates

• First Submitted: May 18, 2006
• First Submitted That Met QC Criteria: May 18, 2006
• First Posted (ESTIMATE): May 19, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): February 17, 2011
• Last Update Submitted That Met QC Criteria: February 16, 2011
• Last Verified: March 1, 2007

More Information

Terms related to this study

• Keywords: inborn errors of metabolism; FAO disorders; long-chain FAO enzyme defects; 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: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors
• Other Study ID Numbers: P030435