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

Inborn Errors of Metabolism Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00328159
• Other study ID #: P030435
• Status: Completed
• Phase: N/A
• First received: May 18, 2006
• Last updated: February 16, 2011
• Start date: June 2006
• Est. completion date: June 2010

Study information

• Verified date: March 2007
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Inborn Errors of Metabolism
• Metabolism, Inborn Errors

Intervention

Drug:
• Oil special 107 and MYGLIOL 810

Locations

Country	Name	City	State
France	Necker University Hospital - Metabolism Unit	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Strength tests		24 months	Yes
Primary	Biological parameters (acylcarnitines profile, modifications of urinary organic acids)		24 months	Yes
Primary	Clinical parameters (echocardiography)		24 months	Yes
Secondary	Ergometric testing		24 months	Yes
Secondary	Hepatic functions		24 months	Yes
Secondary	Hypoglycaemia		24 months	Yes
Secondary	Rhabdomyolyses		24 months	Yes