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| Sponsor: | University Hospital, Tours |
|---|---|
| Information provided by: | University Hospital, Tours |
| ClinicalTrials.gov Identifier: | NCT00841295 |
Purpose
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.
| Condition | Intervention |
|---|---|
|
Prematurity |
Drug: Parenteral L-carnitine supplementation Drug: Parenteral supplementation with sterile water |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Prevention |
| Official Title: | Effects of Parenteral L-carnitine Supplementation in Premature Neonates |
| Estimated Enrollment: | 80 |
| Study Start Date: | July 2008 |
| Estimated Study Completion Date: | July 2013 |
| Estimated Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 1
Parenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source.
|
Drug: Parenteral L-carnitine supplementation
Parenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source.
|
|
Placebo Comparator: 2
Parenteral supplementation with an equivalent volume of sterile water
|
Drug: Parenteral supplementation with sterile water
Parenteral supplementation with an equivalent volume of sterile water
|
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.
Primary Outcome: Plasma Gamma Glutamyl Transferase level after 21 days of parenteral supplementation.
Secondary Outcomes: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcomes: 1) Liver function (levels of ammonemia, hyaluronic acid, bilirubin, prothrombin time test, ursodeoxycholic acid therapy), 2) cardiac function (echocardiography, EKG), 3) muscle integrity (CK levels), 4) neurological injuries (brain ultrasound and MRI), 5) respiratory immaturity, 6) acylcarnitine profile and other fatty acid derivatives.
Expected Findings: Systematic parenteral carnitine supplementation will prevent systemic carnitine deficiency, and will improve liver dysfunction (decreased duration and severity of liver disease) associated with prolonged parenteral nutrition, will improve cardiac and muscle functions, and will prevent cerebral injury in premature infants with very low birth weight.
Eligibility| Ages Eligible for Study: | up to 28 Weeks |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contacts and Locations| Contact: François LABARTHE, MD | +33 2 47 47 38 18 | labarthe@med.univ-tours.fr |
| France | |
| UH Porte Madeleine | Recruiting |
| Orleans, France | |
| Contact: Evelyne WERNER MELLUL, MD (33) 2.38.74.42.80 evelyne.werner@chr-orleans.fr | |
| Contact: Marie ROUJOU-GRIS, MD (33) 2 38 61 31 59 marie.roujou-gris@chr-orleans.fr | |
| Principal Investigator: Evelyne WERNER MELLUL, MD | |
| Sub-Investigator: Marie Roujou Gris, MD | |
| Hôpital Clocheville, University Hospital, Tours | Recruiting |
| Tours, France | |
| Contact: François LABARTHE, MD +33 2 47 47 38 18 labarthe@med.univ-tours.fr | |
| Principal Investigator: François LABARTHE, MD | |
| Sub-Investigator: Aude CHEMIN, MD | |
| Principal Investigator: | François LABARTHE, MD | University Hospital, Tours |
More Information
| Responsible Party: | Directrice des Affaires Médicales et de la Recherche, CHRU de Tours |
| ClinicalTrials.gov Identifier: | NCT00841295 History of Changes |
| Other Study ID Numbers: | PHRI06-FL / CARNIPREMA, N° EudraCT: 2007-002446-37, Réf.CPP: 2007-R24, Réf.Afssaps: A70583-46 |
| Study First Received: | February 10, 2009 |
| Last Updated: | May 31, 2011 |
| Health Authority: | France: Afssaps - French Health Products Safety Agency |
|
Carnitine Vitamin B Complex Vitamins Micronutrients |
Growth Substances Physiological Effects of Drugs Pharmacologic Actions |
