Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
Sponsor
Montefiore Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT01783041
Collaborator
The Gerber Foundation (Other)
144
2
2
107.9
72
0.7
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2/Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
144 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
A Double-Blind, Controlled, Randomized Clinical Trial of the Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
Study Start Date
:
Jan 1, 2013
Actual Primary Completion Date
:
Dec 1, 2020
Actual Study Completion Date
:
Dec 28, 2021
Arms and Interventions
| 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:
|
Outcome Measures
Primary Outcome Measures
- Time to Regain Birthweight in Infants Who Receive L-carnitine Supplementation Compared to Controls [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) [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).
Secondary Outcome Measures
- White Matter Development, Brain Volumes and Brain Metabolism in Infants Who Received L-carnitine Supplementation Compared to Controls [Data being analyzed, will be updated by December, 2022]
Brain MRI findings including white matter development and brain metabolism were compared in infants who received L-carnitine supplementation compared to controls.
- Rate of Head Growth in Infants Who Receive L-carnitine Supplementation Compared to Controls [36 weeks corrected age]
Head circumference was measured at 36 weeks corrected age in both study groups (L-carnitine vs. placebo).
Eligibility Criteria
Criteria
Ages Eligible for Study:
1 Day
to 3 Days
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Montefiore Medical Center - Jack D. Weiler Division | Bronx | New York | United States | 10461 |
| 2 | Montefiore Medical Center - Wakefield Division | Bronx | New York | United States | 10466 |
Sponsors and Collaborators
- Montefiore Medical Center
- The Gerber Foundation
Investigators
- Principal Investigator: Mamta Fuloria, MD, Montefiore Medical Center
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Montefiore Medical Center
ClinicalTrials.gov Identifier:
NCT01783041
Other Study ID Numbers:
- 12-07-234
First Posted:
Feb 4, 2013
Last Update Posted:
Jul 28, 2022
Last Verified:
Jul 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Montefiore Medical Center
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Infants born at <32 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) at Weiler and Wakefield Divisions of Montefiore Medical Center were enrolled in this study. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 5% Dextrose | L-carnitine |
|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. |
| Period Title: First 2 Weeks of Life | ||
| STARTED | 72 | 72 |
| COMPLETED | 69 | 71 |
| NOT COMPLETED | 3 | 1 |
| Period Title: First 2 Weeks of Life | ||
| STARTED | 69 | 71 |
| COMPLETED | 60 | 59 |
| NOT COMPLETED | 9 | 12 |
Baseline Characteristics
| Arm/Group Title | 5% Dextrose | L-carnitine | Total |
|---|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. | Total of all reporting groups |
| Overall Participants | 72 | 72 | 144 |
| Age (Count of Participants) | |||
| <=18 years |
72
100%
|
72
100%
|
144
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
36
50%
|
34
47.2%
|
70
48.6%
|
| Male |
36
50%
|
38
52.8%
|
74
51.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
35
48.6%
|
37
51.4%
|
72
50%
|
| Not Hispanic or Latino |
33
45.8%
|
32
44.4%
|
65
45.1%
|
| Unknown or Not Reported |
4
5.6%
|
3
4.2%
|
7
4.9%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
2
2.8%
|
3
4.2%
|
5
3.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
30
41.7%
|
28
38.9%
|
58
40.3%
|
| White |
38
52.8%
|
40
55.6%
|
78
54.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
2
2.8%
|
1
1.4%
|
3
2.1%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
72
100%
|
72
100%
|
144
100%
|
Outcome Measures
| Title | Time to Regain Birthweight in Infants Who Receive L-carnitine Supplementation Compared to Controls |
|---|---|
| Description | Time (in days) for infants in both arms of the study to regain birthweight - data presented as mean +/- SD. |
| Time Frame | up to 3 weeks of age |
Outcome Measure Data
| Analysis Population Description |
|---|
| The discrepancy in the number of infants enrolled in each arm of the study and the number with data for this outcome is because of early deaths in the study as well as some parents withdrawing consent from the study. |
| Arm/Group Title | 5% Dextrose | L-carnitine |
|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. |
| Measure Participants | 68 | 68 |
| Mean (Standard Deviation) [days] |
8.12
(3.5)
|
8.4
(3.3)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 5% Dextrose, L-carnitine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | These are calculated p values. | |
| Method | ANOVA | |
| Comments | Differences in continuous and categorical variables were compared using ANOVA and either Chi square test or Fisher's exact test, respectively. | |
| Title | Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS) |
|---|---|
| Description | 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). |
| Time Frame | at term equivalent age (38 weeks +/-1 week corrected age) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The discrepancy in the numbers analyzed for this outcome compared to the enrolled participants in each study arm is related to: (1) mortality, (2) parents revoking consent, and (3) some patients were too sick for this evaluation to be performed. |
| Arm/Group Title | 5% Dextrose | L-carnitine |
|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. |
| Measure Participants | 60 | 59 |
| Attention |
4.66
(1.62)
|
4.29
(1.41)
|
| Stress abstinence |
0.073
(0.074)
|
0.079
(0.064)
|
| Quality of Movement |
4.6
(0.63)
|
4.6
(0.64)
|
| Arousal |
3.95
(0.6)
|
3.93
(0.61)
|
| Regulation |
5.5
(0.77)
|
5.5
(0.84)
|
| Handling |
0.35
(0.28)
|
0.36
(0.23)
|
| Hypertonicity |
0.12
(0.32)
|
0.14
(0.43)
|
| Hypotonicity |
0.57
(0.87)
|
0.22
(0.46)
|
| Asymmetrical Reflexes |
0.35
(0.79)
|
0.37
(0.72)
|
| Non-Optimal Reflexes |
3.95
(2.25)
|
4.2
(2.2)
|
| Excitability |
2.6
(2)
|
2.59
(1.99)
|
| Lethargy |
4.8
(3)
|
5.2
(2.6)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 5% Dextrose, L-carnitine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | These are calculated p values. | |
| Method | Wilcoxon (Mann-Whitney) | |
| Comments | This analysis applies to all sub-scales that were compared between the 2 study groups. | |
| Title | White Matter Development, Brain Volumes and Brain Metabolism in Infants Who Received L-carnitine Supplementation Compared to Controls |
|---|---|
| Description | Brain MRI findings including white matter development and brain metabolism were compared in infants who received L-carnitine supplementation compared to controls. |
| Time Frame | Data being analyzed, will be updated by December, 2022 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Rate of Head Growth in Infants Who Receive L-carnitine Supplementation Compared to Controls |
|---|---|
| Description | Head circumference was measured at 36 weeks corrected age in both study groups (L-carnitine vs. placebo). |
| Time Frame | 36 weeks corrected age |
Outcome Measure Data
| Analysis Population Description |
|---|
| The discrepancy in the number of infants enrolled in each arm of the study and the number with data for this outcome is because of early deaths in the study as well as some parents withdrawing consent from the study. |
| Arm/Group Title | 5% Dextrose | L-carnitine |
|---|---|---|
| Arm/Group Description | 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. 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. | 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. 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. |
| Measure Participants | 68 | 68 |
| Mean (Standard Deviation) [centimeters] |
30.6
(1.68)
|
30.4
(1.76)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 5% Dextrose, L-carnitine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.05 |
| Comments | These are calculated p values. | |
| Method | ANOVA | |
| Comments | Differences in continuous and categorical variables were compared using ANOVA and either Chi square test or Fisher's exact test, respectively. | |
Adverse Events
| Time Frame | Until hospital discharge, generally upto approximately 44 weeks post-menstrual age. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | 5% Dextrose | L-carnitine | ||
| Arm/Group Description | 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. 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. | 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. 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. | ||
All Cause Mortality |
||||
| 5% Dextrose | L-carnitine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/72 (4.2%) | 1/72 (1.4%) | ||
Serious Adverse Events |
||||
| 5% Dextrose | L-carnitine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/72 (25%) | 24/72 (33.3%) | ||
| Cardiac disorders | ||||
| Patent ductus arteriosus | 18/72 (25%) | 18 | 24/72 (33.3%) | 24 |
| Gastrointestinal disorders | ||||
| Surgical necrotizing entercolitis | 0/72 (0%) | 0 | 1/72 (1.4%) | 1 |
| Nervous system disorders | ||||
| Intraventricular hemorrhage | 3/72 (4.2%) | 3 | 3/72 (4.2%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchopulmonary Dysplasia | 14/72 (19.4%) | 14 | 23/72 (31.9%) | 23 |
Other (Not Including Serious) Adverse Events |
||||
| 5% Dextrose | L-carnitine | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/72 (5.6%) | 9/72 (12.5%) | ||
| Infections and infestations | ||||
| Blood culture positive sepsis | 4/72 (5.6%) | 4 | 9/72 (12.5%) | 9 |
Limitations/Caveats
This is a single center study.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Mamta Fuloria |
|---|---|
| Organization | Children's Hospital at Montefiore, Albert Einstein College of Medicine |
| Phone | 718-904-4105 |
| mfuloria@montefiore.org |
Responsible Party:
Montefiore Medical Center
ClinicalTrials.gov Identifier:
NCT01783041
Other Study ID Numbers:
- 12-07-234
First Posted:
Feb 4, 2013
Last Update Posted:
Jul 28, 2022
Last Verified:
Jul 1, 2022