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Effects of Parenteral L-carnitine Supplementation in Premature Neonates (CarniPrema)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Tours
ClinicalTrials.gov Identifier:
NCT00841295
First received: February 10, 2009
Last updated: October 29, 2013
Last verified: February 2011
  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
Complication of 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Tours:

Primary Outcome Measures:
  • Plasma Gamma Glutamyl Transferase level [ Time Frame: After 21 days of parenteral supplementation. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Liver function: levels of ammonemia, hyaluronic acid, bilirubin, prothrombin time test, use of ursodeoxycholic acid therapy. [ Time Frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome ] [ Designated as safety issue: No ]
  • Cardiac function: echocardiography, EKG. [ Time Frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome ] [ Designated as safety issue: No ]
  • Muscle integrity: CK levels. [ Time Frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome ] [ Designated as safety issue: No ]
  • Neurological injuries: brain ultrasound and MRI. [ Time Frame: Short- (during parenteral supplementation, ultrasound) and long- (3 to 5 months of age, MRI) term outcome ] [ Designated as safety issue: No ]
  • Respiratory immaturity [ Time Frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome ] [ Designated as safety issue: No ]
  • Acylcarnitine profile, and other fatty acid derivative levels. [ Time Frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome ] [ Designated as safety issue: No ]

Enrollment: 53
Study Start Date: July 2008
Study Completion Date: July 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carnitine
Intervention '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 L-carnitine supplementation
Parenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source.
Placebo Comparator: Controle
Intervention 'Parenteral supplementation with sterile water'
Drug: Parenteral supplementation with sterile water
Parenteral supplementation with an equivalent volume of sterile water

Detailed Description:

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
Criteria

Inclusion Criteria:

  • Premature newborn admitted in Intensive Care Unit,
  • Gestational age minor or equal than 28 weeks and 6 days,
  • Needing prolonged parenteral nutrition through a central intravenous catheter,
  • Parenteral nutrition started before 6 days of life,
  • Both parents (or legal tutor) gave written informed consent for their children,
  • Patient affiliated to "Sécurité Sociale" of his parents.

Exclusion Criteria:

  • Severe associated disorder, with a probable short-term death,
  • Identified genetic disease,
  • Polymalformative syndrome, or severe malformation (heart, brain, others…),
  • Inborn error of metabolism,
  • Probable transfer of the subject before 25 days of life in another hospital that do not collaborate to this study.
  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: NCT00841295

Locations
France
UH Porte Madeleine
Orleans, France
Hôpital Clocheville, University Hospital, Tours
Tours, France
Sponsors and Collaborators
University Hospital, Tours
Investigators
Principal Investigator: François LABARTHE, MD University Hospital, Tours
  More Information

No publications provided

Responsible Party: University Hospital, 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: October 29, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Additional relevant MeSH terms:
Premature Birth
Obstetric Labor Complications
Obstetric Labor, Premature
Pregnancy Complications
Carnitine
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Vitamin B Complex
Vitamins

ClinicalTrials.gov processed this record on November 20, 2014