PrematurityPhase 2/3NCT01783041
Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
A Phase 2/3 study testing L-carnitine and 5% Dextrose in people with Prematurity and Neurodevelopmental Disorder, run by Montefiore Medical Center at 2 sites in United States.
Trial summary
Preterm infants are vulnerable to brain injury, nutritional deficiencies and poor early growth which places them at increased risk for developmental problems later in life. The micronutrient carnitine, which is present in breast milk and stored in the fetus late in pregnancy, has been shown to protect against brain… Read more about this study
- Who is it for?
- Ages 1 day to 3 days
- Conditions the study is for
- Prematurity, Neurodevelopmental Disorder, Carnitine Deficiency
- What is being tested?
- L-carnitine and 5% Dextrose
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2013to 28 Dec 2021
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 day to 3 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants born at equal to or less than 30 weeks gestation and with birth weight < 1250 grams
- Less than 72 hours of age
- Signed parental consent
Who cannot join
- Critically ill infants with life expectancy less than 72 hours
- Inability to obtain consent within 72 hours of birth
- Potentially life-threatening congenital anomalies
- Known hereditary metabolic disorders
- Known chromosomal abnormalities
- Terratogen exposure with symptomatic substance withdrawal
Show all 9Show fewer
- Congenital viral infections
- Microcephaly
- Grade IV intraventricular hemorrhage or seizures documented within the first 72 hours of life
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Montefiore Medical Center - Jack D. Weiler Division
The Bronx, New York, 10461
Montefiore Medical Center - Wakefield Division
The Bronx, New York, 10466
About this study
Official title: A Double-Blind, Controlled, Randomized Clinical Trial of the Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
Preterm infants are vulnerable to brain injury, nutritional deficiencies and poor early growth which places them at increased risk for developmental problems later in life. The micronutrient carnitine, which is present in breast milk and stored in the fetus late in pregnancy, has been shown to protect against brain injury in animal studies. Without supplementation, almost all preterm infants develop carnitine deficiency soon after birth. Thus it is important to determine if carnitine supplementation protects against brain injury and improves developmental outcomes in these vulnerable preterm infants. We hypothesize that preterm infants supplemented early with L-carnitine while receiving parenteral nutrition will not develop carnitine deficiency and will have improved growth in the first two weeks of life and higher scores on developmental tests when compared to control infants who did not receive carnitine.
Read the detailed description
Hypothesis: We hypothesize that preterm infants supplemented with early physiologic doses of L-carnitine while on parenteral nutrition will have improved short-term growth parameters and significantly higher neurobehavioral scores when compared with control infants.
Methods/Design: This is a prospective, randomized controlled clinical trial involving infants with gestational age (GA) <32 wks who are born at either the Jack D. Weiler Hospital or the Wakefield Division of Montefiore and admitted to theirNeonatal Intensive Care Unit. Informed consent will be obtained from the parents of eligible patients as early as possible within 72 hours of birth. Infants whose parents have signed an informed consent form will be randomized to receive either carnitine supplementation (50 μmol/kg/day) versus placebo within 72-96 hours of birth.
Randomization: As previously described by Pande et al., enrolled patients will be randomized to either the treatment group (L-carnitine, 50 μmol/kg/day) or placebo group (5% glucose, similar volume as the L-carnitine group).28 Patients who meet study entry criteria and have signed informed parental/guardian consent will be enrolled in the study. Because gestational age and small for gestational age (SGA) status will impact our outcome measures, we will ensure they are equally distributed in the arms of the study by stratifying based upon these variables. We will analyze the two study arms using an intent-to-treat analysis. Therefore, enrolled patients will be stratified into fourgroups: gestational age 23 to 26 6/7 weeks, gestational age 27 to 29 6/7weeks, gestational age 30 to 31 6/7 weeks and small for gestational age (SGA). Patients within each stratum will be randomized by the pharmacist using a computerized block-generation with sets of 4. In the case of multiple births, all infants must meet study criteria, and the infants will be randomized as a set. One infant of the multiple-birth set will be randomly chosen for inclusion in the analysis. A recruitment log of all screened infants will be maintained. Clinicians and the nursing staff will be unaware of the arm of the treatment protocol to which the patient is assigned. Codes will be unblinded only after all patients have reached the study end-point, or at the request of the Data Safety Monitoring Board.
Study supplementation: Infants randomized to the treatment group will receive 50 μmol/kg/day of L-carnitine intravenously for 2 weeks, and infants randomized to placebo will received 5% glucose, similar volume to the L-carnitine group. At two weeks, sufficient carnitine is provided in enteral feeds of either breast milk or infant formula. If no intravenous access is available before the supplementation endpoint, the equivalent dose of enteral study supplement (L-carnitine or placebo) will be administered.41 Parenteral and enteral nutrition will be provided according to standard NICU protocol.
Of note, as many as 10% of the infants in the study will likely continue to rely primarily on parenteral nutrition beyond the proposed two-week supplementation period. Enteral feeds may be withheld from these infants due to underlying illnesses such as sepsis or gastrointestinal disorders like necrotizing enterocolitis. Due to the presence of underlying illness, these infants are at an even higher risk for developing developmental delays. Therefore, in study patients who are not receiving adequate enteral nutrition (100 cc/kg/day of enteral intake) after 2-weeks of study supplements, carnitine supplementation will be continued until these infant are receiving adequate enteral feeds; at this point, their physiologic carnitine requirements will be met by enteral nutrition alone.
- Being tested
- L-carnitine, 5% Dextrose
- Keywords
- Prematurity, Carnitine supplementation, Neonatal Intensive Care, MRI, Amplitude-integrated EEG, NICU Network Neurobehavioral Scale, Bayley Scale of Infant Development III
- Medical subject headings
- Premature Birth, Neurodevelopmental Disorders, Systemic carnitine deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-carnitineDrug
Also called Levocarnitine, Carnitor
Infants will receive L-carnitine 50 micromoles/kg/day, divided into three doses, intravenously for a minimum of 2 weeks or until they achieve enteral feeding volume of 100 cc/kg/day. If infant is receiving 100 cc/kg/day of enteral feeds before the supplementation endpoint, an equivalent dose of enteral L-carnitine will be given to the study patients.
5% DextroseDrug
Infants will receive 5% dextrose (placebo) three times a day (volume equivalent to the experimental drug) intravenously for a minimum of 2 weeks or until they achieve enteral feeding volume of 100 cc/kg/day. If infant is receiving 100 cc/kg/day of enteral feeds before the supplementation endpoint, an equivalent volume of enteral placebo (5% Dextrose) will be given to the study patients.
| Study group | Role | What they receive |
|---|---|---|
| 5% dextrose | Placebo comparator | Infants randomized to the placebo group will receive 5% dextrose intravenously. If infant is receiving 100 cc/kg/day of enteral feeds before the supplementation endpoint, an equivalent volume of placebo (5% Dextrose) will be given to the study patients. Receives: Drug: 5% Dextrose |
| L-carnitine | Experimental | Infants randomized to the study group will receive L-carnitine intravenously. If infant is receiving 100 cc/kg/day of enteral feeds before the supplementation endpoint, an equivalent dose of enteral L-carnitine will be given to the study patients. Receives: Drug: L-carnitine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Regain Birthweight in Infants Who Receive L-carnitine Supplementation Compared to Controls
Time (in days) for infants in both arms of the study to regain birthweight - data presented as mean +/- SD.
Measured: up to 3 weeks of age
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
NICU Network Neurobehavioral Scale (NNNS) was administered to study participants at term equivalent age (38 weeks +/-1 week corrected age). The NNNS is a 128-item standardized assessment to evaluate the neurobehavioral status of healthy and high-risk infants. Summary scores include: Attention (range 2.25-8; higher score better), Arousal (range 2-5; lower score better), Regulation (range 3.31-6.92; higher score better), Handling (range 0-0.88; lower score better), Quality of movement (range 3-6; higher score better), Excitability (range 0-9; lower score better), Lethargy (range 0-12; lower score better), Nonoptimal reflexes (range 0-10; lower score better), Asymmetric reflexes (range 0-6; lower score better), Hypertonicity (range 0-2; lower score better), Hypotonicity (range 0-3; lower score better), and Stress/abstinence scale (range 0-0.22; lower score better).
Measured: at term equivalent age (38 weeks +/-1 week corrected age)
Secondary outcomes (2)
Brain Volumes in Infants Who Received L-carnitine Supplementation Compared to Controls
Brain MRI findings including brain volumes of the cerebellum, thalamus and basal ganglia were compared in infants who received L-carnitine supplementation compared to controls.
Measured: at corrected age (38 weeks +/- 1 week)
Rate of Head Growth in Infants Who Receive L-carnitine Supplementation Compared to Controls
Head circumference was measured at 36 weeks corrected age in both study groups (L-carnitine vs. placebo).
Measured: 36 weeks corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2013 (estimated)
- Study startJan 2013
- Primary completionDec 2020
- Study completion28 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for PrematurityStudies of the same condition, open and under way.
- More trials run by Montefiore Medical CenterThe 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 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montefiore Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Gerber Foundation
- Responsible party
- Sponsor
- Investigators
- Mamta Fuloria, MD, Principal investigator, Montefiore Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01783041
- Sponsor's protocol ID
- 12-07-234
- Status last verified
- Feb 2023
- First submitted
- 25 Jan 2013
- Last updated
- 8 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Controlled, Randomized Clinical Trial of the Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
- ClinicalTrials.gov ID
- NCT01783041
- Acronym / sponsor ID
- 12-07-234
- Keywords
- Prematurity, Carnitine supplementation, Neonatal Intensive Care, MRI, Amplitude-integrated EEG, NICU Network Neurobehavioral Scale, Bayley Scale of Infant Development III
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Montefiore Medical CenterUniversity, hospital or other
- Collaborators
- The Gerber Foundation
- Study start
- Jan 2013
- Primary completion
- Dec 2020 (actual)
- Study completion
- 28 Dec 2021 (actual)
- First posted
- 4 Feb 2013 (estimated)
- Results
- Posted 8 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Preterm infants are vulnerable to brain injury, nutritional deficiencies and poor early growth which places them at increased risk for developmental problems later in life. The micronutrient carnitine, which is present in breast milk and stored in the fetus late in pregnancy, has been shown to protect against brain injury in animal studies. Without supplementation, almost all preterm infants develop carnitine deficiency soon after birth. Thus it is important to determine if carnitine supplementation protects against brain injury and improves developmental outcomes in these vulnerable preterm infants. We hypothesize that preterm infants supplemented early with L-carnitine while receiving parenteral nutrition will not develop carnitine deficiency and will have improved growth in the first two weeks of life and higher scores on developmental tests when compared to control infants who did not receive carnitine.
Detailed description
Hypothesis: We hypothesize that preterm infants supplemented with early physiologic doses of L-carnitine while on parenteral nutrition will have improved short-term growth parameters and significantly higher neurobehavioral scores when compared with control infants.
Methods/Design: This is a prospective, randomized controlled clinical trial involving infants with gestational age (GA) <32 wks who are born at either the Jack D. Weiler Hospital or the Wakefield Division of Montefiore and admitted to theirNeonatal Intensive Care Unit. Informed consent will be obtained from the parents of eligible patients as early as possible within 72 hours of birth. Infants whose parents have signed an informed consent form will be randomized to receive either carnitine supplementation (50 μmol/kg/day) versus placebo within 72-96 hours of birth.
Randomization: As previously described by Pande et al., enrolled patients will be randomized to either the treatment group (L-carnitine, 50 μmol/kg/day) or placebo group (5% glucose, similar volume as the L-carnitine group).28 Patients who meet study entry criteria and have signed informed parental/guardian consent will be enrolled in the study. Because gestational age and small for gestational age (SGA) status will impact our outcome measures, we will ensure they are equally distributed in the arms of the study by stratifying based upon these variables. We will analyze the two study arms using an intent-to-treat analysis. Therefore, enrolled patients will be stratified into fourgroups: gestational age 23 to 26 6/7 weeks, gestational age 27 to 29 6/7weeks, gestational age 30 to 31 6/7 weeks and small for gestational age (SGA). Patients within each stratum will be randomized by the pharmacist using a computerized block-generation with sets of 4. In the case of multiple births, all infants must meet study criteria, and the infants will be randomized as a set. One infant of the multiple-birth set will be randomly chosen for inclusion in the analysis. A recruitment log of all screened infants will be maintained. Clinicians and the nursing staff will be unaware of the arm of the treatment protocol to which the patient is assigned. Codes will be unblinded only after all patients have reached the study end-point, or at the request of the Data Safety Monitoring Board.
Study supplementation: Infants randomized to the treatment group will receive 50 μmol/kg/day of L-carnitine intravenously for 2 weeks, and infants randomized to placebo will received 5% glucose, similar volume to the L-carnitine group. At two weeks, sufficient carnitine is provided in enteral feeds of either breast milk or infant formula. If no intravenous access is available before the supplementation endpoint, the equivalent dose of enteral study supplement (L-carnitine or placebo) will be administered.41 Parenteral and enteral nutrition will be provided according to standard NICU protocol.
Of note, as many as 10% of the infants in the study will likely continue to rely primarily on parenteral nutrition beyond the proposed two-week supplementation period. Enteral feeds may be withheld from these infants due to underlying illnesses such as sepsis or gastrointestinal disorders like necrotizing enterocolitis. Due to the presence of underlying illness, these infants are at an even higher risk for developing developmental delays. Therefore, in study patients who are not receiving adequate enteral nutrition (100 cc/kg/day of enteral intake) after 2-weeks of study supplements, carnitine supplementation will be continued until these infant are receiving adequate enteral feeds; at this point, their physiologic carnitine requirements will be met by enteral nutrition alone.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5% dextrose | Placebo comparator | Drug: 5% DextroseInfants randomized to the placebo group will receive 5% dextrose intravenously. If infant is receiving 100 cc/kg/day of enteral feeds before the supplementation endpoint, an equivalent volume of placebo (5% Dextrose) will be given to the study patients. |
| L-carnitine | Experimental | Drug: L-carnitineInfants randomized to the study group will receive L-carnitine intravenously. If infant is receiving 100 cc/kg/day of enteral feeds before the supplementation endpoint, an equivalent dose of enteral L-carnitine will be given to the study patients. |
Who may qualify
- Ages
- 1 day to 3 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Infants born at equal to or less than 30 weeks gestation and with birth weight < 1250 grams
- Less than 72 hours of age
- Signed parental consent
Key exclusion criteria (9 listed)
- Critically ill infants with life expectancy less than 72 hours
- Inability to obtain consent within 72 hours of birth
- Potentially life-threatening congenital anomalies
- Known hereditary metabolic disorders
- Known chromosomal abnormalities
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 |
|---|---|---|
| L-carnitineAlso: Levocarnitine, CarnitorInfants will receive L-carnitine 50 micromoles/kg/day, divided into three doses, intravenously for a minimum of 2 weeks or until they achieve enteral feeding volume of 100 cc/kg/day. If infant is receiving 100 cc/kg/day of enteral feeds before the supplementation endpoint, an equivalent dose of enteral L-carnitine will be given to the study patients. | Drug | L-carnitine |
| 5% DextroseInfants will receive 5% dextrose (placebo) three times a day (volume equivalent to the experimental drug) intravenously for a minimum of 2 weeks or until they achieve enteral feeding volume of 100 cc/kg/day. If infant is receiving 100 cc/kg/day of enteral feeds before the supplementation endpoint, an equivalent volume of enteral placebo (5% Dextrose) will be given to the study patients. | Drug | 5% dextrose |
Primary outcome
Time to Regain Birthweight in Infants Who Receive L-carnitine Supplementation Compared to Controls
Time frame: up to 3 weeks of age
Time (in days) for infants in both arms of the study to regain birthweight - data presented as mean +/- SD.
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Time frame: at term equivalent age (38 weeks +/-1 week corrected age)
NICU Network Neurobehavioral Scale (NNNS) was administered to study participants at term equivalent age (38 weeks +/-1 week corrected age). The NNNS is a 128-item standardized assessment to evaluate the neurobehavioral status of healthy and high-risk infants. Summary scores include: Attention (range 2.25-8; higher score better), Arousal (range 2-5; lower score better), Regulation (range 3.31-6.92; higher score better), Handling (range 0-0.88; lower score better), Quality of movement (range 3-6; higher score better), Excitability (range 0-9; lower score better), Lethargy (range 0-12; lower score better), Nonoptimal reflexes (range 0-10; lower score better), Asymmetric reflexes (range 0-6; lower score better), Hypertonicity (range 0-2; lower score better), Hypotonicity (range 0-3; lower score better), and Stress/abstinence scale (range 0-0.22; lower score better).
2 secondary outcomes
Brain Volumes in Infants Who Received L-carnitine Supplementation Compared to Controls
Time frame: at corrected age (38 weeks +/- 1 week)
Rate of Head Growth in Infants Who Receive L-carnitine Supplementation Compared to Controls
Time frame: 36 weeks corrected age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Mamta Fuloria, MD principal investigator
Montefiore Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing L-carnitine and 5% Dextrose in people with Prematurity and Neurodevelopmental Disorder, run by Montefiore Medical Center at 2 sites in United States.
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 3 inclusion and 9 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 8 Mar 2023. 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 United States. 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.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Regain Birthweight in Infants Who Receive L-carnitine Supplementation Compared to Controls (time frame: up to 3 weeks of age). The study lists 2 primary outcomes in all. 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 8 Mar 2023.