Effects of Parenteral L-carnitine Supplementation in Premature Neonates

Summary

Background: Carnitine is the essential cofactor for various enzyme activities of human metabolism, especially for the mitochondrial carnitine shuttle that transfers long-chain fatty acids as acylcarnitine esters across the inner mitochondrial membrane for Beta-oxidation and energy production. Intracellular carnitine deficiency induces an impairment of long-chain fatty acid oxidation. In human, approximately 75% of carnitine comes from the diet and 25% from endogenous liver synthesis. In the neonatal period, more specifically in the premature, liver synthesis capacity is reduced because of immaturity of the biosynthetic pathway, and carnitine levels are related to exogenous sources. Traditionally, carnitine is not added to parenteral nutrition. Indeed, without enteral feeds and carnitine supplementation of parenteral nutrition, preterm infants' plasma carnitine levels fall during the first weeks of life, particularly in subjects requiring a prolonged exclusive parenteral nutrition. The potential deleterious role of carnitine deficiency has not been clearly demonstrated in these infants. However, most patients with primary carnitine deficiency, a genetic defect of carnitine transport inducing a severe carnitine deficiency, commonly develop liver symptoms (encompassing visceral steatosis, hyperammonemia and recurrent hypoketotic hypoglycemias) and/or cardiomyopathy and myopathy. In these latter patients, carnitine supplementation improves all the symptoms.

Hypothesis: Carnitine deficiency of the premature and very low birth weight infants may be one of the factors involved in the liver disease frequently associated with prolonged parenteral nutrition, and may have deleterious effects on cardiac and muscle metabolism and functions.

Aims: To demonstrate beneficial effects of parenteral carnitine supplementation in premature neonates for liver, heart and muscle metabolism and functions.

Study Type: Multicentric prospective and randomised study

Subjects: Premature and very low birth weight neonates, defined by gestational age minor or equal to 28 weeks and/or birth weight minor or equal to 1000 grams, 80 subjects will be enrolled during 2.5 years

Interventions: Arm 1 (experimental): parenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source; Arm 2 (Placebo comparator): parenteral supplementation with an equivalent volume of sterile water.

Conditions

• Complication of Prematurity

Interventions

DRUG

Parenteral L-carnitine supplementation

Parenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source.

DRUG

Parenteral supplementation with sterile water

Parenteral supplementation with an equivalent volume of sterile water

Sponsors & Collaborators

• University Hospital, Tours

  lead OTHER

Principal Investigators

• François LABARTHE, MD · University Hospital, Tours

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

PARALLEL

Eligibility

Max Age

28 Weeks

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-07-31

Primary Completion

2013-03-31

Completion

2013-07-31

Countries

• France

Study Locations