Complication of PrematurityCarniPremaNCT00841295
Effects of Parenteral L-carnitine Supplementation in Premature Neonates
A study testing Parenteral L-carnitine supplementation and Parenteral supplementation with sterile water in people with Complication of Prematurity, run by University Hospital, Tours at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 28 weeks
- Conditions the study is for
- Complication of Prematurity
- What is being tested?
- Parenteral L-carnitine supplementation and Parenteral supplementation with sterile water
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 2 sitesFrance
- Study dates
- Jul 2008to Jul 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 28 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country.
France2 sites
UH Porte Madeleine
Orléans
Hôpital Clocheville, University Hospital, Tours
Tours
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Complication of Prematurity
- Being tested
- Parenteral L-carnitine supplementation, Parenteral supplementation with sterile water
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Parenteral L-carnitine supplementationDrug
Parenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source.
Parenteral supplementation with sterile waterDrug
Parenteral supplementation with an equivalent volume of sterile water
| Study group | Role | What they receive |
|---|---|---|
| Carnitine | Experimental | Intervention 'Parenteral L-carnitine supplementation' Parenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source. Receives: Drug: Parenteral L-carnitine supplementation |
| Controle | Placebo comparator | Intervention 'Parenteral supplementation with sterile water' Receives: Drug: Parenteral supplementation with sterile water |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Gamma Glutamyl Transferase level
Measured: After 21 days of parenteral supplementation.
Secondary outcomes (6)
Liver function: levels of ammonemia, hyaluronic acid, bilirubin, prothrombin time test, use of ursodeoxycholic acid therapy.
Measured: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Cardiac function: echocardiography, EKG.
Measured: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Muscle integrity: CK levels.
Measured: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Neurological injuries: brain ultrasound and MRI.
Measured: Short- (during parenteral supplementation, ultrasound) and long- (3 to 5 months of age, MRI) term outcome
Respiratory immaturity
Measured: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Acylcarnitine profile, and other fatty acid derivative levels.
Measured: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2009 (estimated)
- Study startJul 2008
- Primary completionMar 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Complication of PrematurityStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- François LABARTHE, MD, Principal investigator, University Hospital, Tours
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00841295
- Sponsor's protocol ID
- PHRI06-FL / CARNIPREMA
- Other IDs
- N° EudraCT: 2007-002446-37, Réf.CPP: 2007-R24, Réf.Afssaps: A70583-46
- Acronym
- CarniPrema
- Status last verified
- Oct 2018
- First submitted
- 10 Feb 2009
- Last updated
- 22 Oct 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Parenteral L-carnitine Supplementation in Premature Neonates
- ClinicalTrials.gov ID
- NCT00841295
- Acronym / sponsor ID
- CarniPrema / PHRI06-FL / CARNIPREMA
- Conditions
- Complication of Prematurity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Mar 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 11 Feb 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carnitine | Experimental | Drug: Parenteral L-carnitine supplementationIntervention 'Parenteral L-carnitine supplementation' Parenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source. |
| Controle | Placebo comparator | Drug: Parenteral supplementation with sterile waterIntervention 'Parenteral supplementation with sterile water' |
Who may qualify
- Ages
- Up to 28 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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,
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Parenteral L-carnitine supplementationParenteral carnitine supplementation (9 ± 1 mg/kg/d), from day 4, until than enteral nutrition provides sufficient carnitine source. | Drug | Carnitine |
| Parenteral supplementation with sterile waterParenteral supplementation with an equivalent volume of sterile water | Drug | Controle |
Primary outcome
Plasma Gamma Glutamyl Transferase level
Time frame: After 21 days of parenteral supplementation.
6 secondary outcomes
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
Cardiac function: echocardiography, EKG.
Time frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Muscle integrity: CK levels.
Time frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Neurological injuries: brain ultrasound and MRI.
Time frame: Short- (during parenteral supplementation, ultrasound) and long- (3 to 5 months of age, MRI) term outcome
Respiratory immaturity
Time frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Acylcarnitine profile, and other fatty acid derivative levels.
Time frame: Short- (during parenteral supplementation) and long- (3 to 5 months of age) term outcome
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
François LABARTHE, MD principal investigator
University Hospital, Tours
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Parenteral L-carnitine supplementation and Parenteral supplementation with sterile water in people with Complication of Prematurity, run by University Hospital, Tours at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma Gamma Glutamyl Transferase level (time frame: After 21 days of parenteral supplementation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2018.