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

NCT01783041 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 12-07-234
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Prematurity; Neurodevelopmental Disorder; Carnitine Deficiency

Keywords

Prematurity; Carnitine supplementation; Neonatal Intensive Care; MRI; Amplitude-integrated EEG; NICU Network Neurobehavioral Scale; Bayley Scale of Infant Development III

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Brain Volumes in Infants Who Received L-carnitine Supplementation Compared to Controls

  at corrected age (38 weeks +/- 1 week)

• Rate of Head Growth in Infants Who Receive L-carnitine Supplementation Compared to Controls

  36 weeks corrected age

Study Arms (2)

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.

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.

Drug: L-carnitine

Interventions

L-carnitine DRUG

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.

Also known as: Levocarnitine, Carnitor

L-carnitine

5% Dextrose DRUG

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.

5% dextrose

Eligibility Criteria

• Age: 1 Day - 3 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Montefiore Medical Center: lead
• The Gerber Foundation: collaborator

Study Sites (2)

Montefiore Medical Center - Jack D. Weiler Division

The Bronx, New York, 10461, United States

Location

Montefiore Medical Center - Wakefield Division

The Bronx, New York, 10466, United States

Location

MeSH Terms

Conditions

Premature Birth; Neurodevelopmental Disorders; Systemic carnitine deficiency

Interventions

Carnitine; Glucose

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Hexoses; Monosaccharides; Sugars; Carbohydrates

Limitations and Caveats

This is a single center study.

Results Point of Contact

• Title: Mamta Fuloria
• Organization: Children's Hospital at Montefiore, Albert Einstein College of Medicine

mfuloria@montefiore.org

718-904-4105

Study Officials

• Mamta Fuloria, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2013
• First Posted: February 4, 2013
• Study Start: January 1, 2013
• Primary Completion: December 1, 2020
• Study Completion: December 28, 2021
• Last Updated: March 8, 2023
• Results First Posted: March 8, 2022

Record last verified: 2023-02

Locations

US (2)