Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants

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.

Study Overview

• Status: Completed
• Conditions: Prematurity; Neurodevelopmental Disorder; Carnitine Deficiency
• Intervention / Treatment: Drug: 5% Dextrose; Drug: L-carnitine

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center - Jack D. Weiler Division
    • Bronx, New York, United States, 10466
      • Montefiore Medical Center - Wakefield Division

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 3 days (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Congenital viral infections
• Microcephaly
• Grade IV intraventricular hemorrhage or seizures documented within the first 72 hours of life

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 5% dextrose; 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.	Drug: 5% Dextrose; 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.
Experimental: L-carnitine; 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.	Drug: L-carnitine; 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.; Other Names: Carnitor; Levocarnitine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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).	at term equivalent age (38 weeks +/-1 week corrected age)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
White Matter Development, Brain Volumes and Brain Metabolism in Infants Who Received L-carnitine Supplementation Compared to Controls	Brain MRI findings including white matter development and brain metabolism were compared in infants who received L-carnitine supplementation compared to controls.	Data being analyzed, will be updated by December, 2022
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).	36 weeks corrected age

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: The Gerber Foundation
• Investigators: Principal Investigator: Mamta Fuloria, MD, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 28, 2021

Study Registration Dates

• First Submitted: January 25, 2013
• First Submitted That Met QC Criteria: January 31, 2013
• First Posted (Estimate): February 4, 2013

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 22, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: MRI; Prematurity; Carnitine supplementation; Neonatal Intensive Care; Amplitude-integrated EEG; NICU Network Neurobehavioral Scale; Bayley Scale of Infant Development III
• Additional Relevant MeSH Terms: Mental Disorders; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Neurodevelopmental Disorders
• Other Study ID Numbers: 12-07-234

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• product manufactured in and exported from the U.S.: Yes