Trial Outcomes & Findings for Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants (NCT NCT01783041)
NCT ID: NCT01783041
Last Updated: 2023-03-08
Results Overview
Time (in days) for infants in both arms of the study to regain birthweight - data presented as mean +/- SD.
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
144 participants
Primary outcome timeframe
up to 3 weeks of age
Results posted on
2023-03-08
Participant Flow
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.
Participant milestones
| Measure |
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.
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.
|
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.
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.
|
|---|---|---|
|
First 2 Weeks of Life
STARTED
|
72
|
72
|
|
First 2 Weeks of Life
COMPLETED
|
69
|
71
|
|
First 2 Weeks of Life
NOT COMPLETED
|
3
|
1
|
|
NNNS Examination at Term Equivalent Age
STARTED
|
69
|
71
|
|
NNNS Examination at Term Equivalent Age
COMPLETED
|
60
|
59
|
|
NNNS Examination at Term Equivalent Age
NOT COMPLETED
|
9
|
12
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
Baseline characteristics by cohort
| Measure |
5% Dextrose
n=72 Participants
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.
|
L-carnitine
n=72 Participants
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
n=144 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
72 Participants
n=93 Participants
|
72 Participants
n=4 Participants
|
144 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=93 Participants
|
34 Participants
n=4 Participants
|
70 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
36 Participants
n=93 Participants
|
38 Participants
n=4 Participants
|
74 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
35 Participants
n=93 Participants
|
37 Participants
n=4 Participants
|
72 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=93 Participants
|
32 Participants
n=4 Participants
|
65 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
30 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
58 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
38 Participants
n=93 Participants
|
40 Participants
n=4 Participants
|
78 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
72 participants
n=93 Participants
|
72 participants
n=4 Participants
|
144 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: up to 3 weeks of agePopulation: 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.
Time (in days) for infants in both arms of the study to regain birthweight - data presented as mean +/- SD.
Outcome measures
| Measure |
5% Dextrose
n=68 Participants
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.
|
L-carnitine
n=68 Participants
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.
|
|---|---|---|
|
Time to Regain Birthweight in Infants Who Receive L-carnitine Supplementation Compared to Controls
|
8.12 days
Standard Deviation 3.5
|
8.4 days
Standard Deviation 3.3
|
PRIMARY outcome
Timeframe: at term equivalent age (38 weeks +/-1 week corrected age)Population: 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.
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).
Outcome measures
| Measure |
5% Dextrose
n=60 Participants
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.
|
L-carnitine
n=59 Participants
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.
|
|---|---|---|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Non-Optimal Reflexes
|
3.95 score on a scale
Standard Deviation 2.25
|
4.2 score on a scale
Standard Deviation 2.2
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Attention
|
4.66 score on a scale
Standard Deviation 1.62
|
4.29 score on a scale
Standard Deviation 1.41
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Stress abstinence
|
0.073 score on a scale
Standard Deviation 0.074
|
0.079 score on a scale
Standard Deviation 0.064
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Quality of Movement
|
4.6 score on a scale
Standard Deviation 0.63
|
4.6 score on a scale
Standard Deviation 0.64
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Arousal
|
3.95 score on a scale
Standard Deviation 0.6
|
3.93 score on a scale
Standard Deviation 0.61
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Regulation
|
5.5 score on a scale
Standard Deviation 0.77
|
5.5 score on a scale
Standard Deviation 0.84
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Handling
|
0.35 score on a scale
Standard Deviation 0.28
|
0.36 score on a scale
Standard Deviation 0.23
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Hypertonicity
|
0.12 score on a scale
Standard Deviation 0.32
|
0.14 score on a scale
Standard Deviation 0.43
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Hypotonicity
|
0.57 score on a scale
Standard Deviation 0.87
|
0.22 score on a scale
Standard Deviation 0.46
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Asymmetrical Reflexes
|
0.35 score on a scale
Standard Deviation 0.79
|
0.37 score on a scale
Standard Deviation 0.72
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Excitability
|
2.6 score on a scale
Standard Deviation 2
|
2.59 score on a scale
Standard Deviation 1.99
|
|
Neurodevelopment Indices in Infants Who Receive L-carnitine Supplementation Compared to Controls (NNNS)
Lethargy
|
4.8 score on a scale
Standard Deviation 3
|
5.2 score on a scale
Standard Deviation 2.6
|
SECONDARY outcome
Timeframe: at corrected age (38 weeks +/- 1 week)Population: Not all enrolled subjects had brain MRIs performed - 63 infants in both study arms had brain MRIs where brain volumes could be calculated.
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.
Outcome measures
| Measure |
5% Dextrose
n=63 Participants
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.
|
L-carnitine
n=63 Participants
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.
|
|---|---|---|
|
Brain Volumes in Infants Who Received L-carnitine Supplementation Compared to Controls
Cerebellar volume
|
19372 milliliters
Standard Deviation 5806
|
18189 milliliters
Standard Deviation 3826
|
|
Brain Volumes in Infants Who Received L-carnitine Supplementation Compared to Controls
Thalamus volume
|
6050 milliliters
Standard Deviation 1139
|
5832 milliliters
Standard Deviation 897
|
|
Brain Volumes in Infants Who Received L-carnitine Supplementation Compared to Controls
Basal ganglia volume
|
8611 milliliters
Standard Deviation 1460
|
8217 milliliters
Standard Deviation 1192
|
SECONDARY outcome
Timeframe: 36 weeks corrected agePopulation: 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.
Head circumference was measured at 36 weeks corrected age in both study groups (L-carnitine vs. placebo).
Outcome measures
| Measure |
5% Dextrose
n=68 Participants
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.
|
L-carnitine
n=68 Participants
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.
|
|---|---|---|
|
Rate of Head Growth in Infants Who Receive L-carnitine Supplementation Compared to Controls
|
30.6 centimeters
Standard Deviation 1.68
|
30.4 centimeters
Standard Deviation 1.76
|
Adverse Events
5% Dextrose
Serious events: 18 serious events
Other events: 4 other events
Deaths: 3 deaths
L-carnitine
Serious events: 24 serious events
Other events: 9 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
5% Dextrose
n=72 participants at risk
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.
|
L-carnitine
n=72 participants at risk
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.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary Dysplasia
|
19.4%
14/72 • Number of events 14 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
31.9%
23/72 • Number of events 23 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
|
Cardiac disorders
Patent ductus arteriosus
|
25.0%
18/72 • Number of events 18 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
33.3%
24/72 • Number of events 24 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
|
Nervous system disorders
Intraventricular hemorrhage
|
4.2%
3/72 • Number of events 3 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
4.2%
3/72 • Number of events 3 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
|
Gastrointestinal disorders
Surgical necrotizing entercolitis
|
0.00%
0/72 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
1.4%
1/72 • Number of events 1 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
Other adverse events
| Measure |
5% Dextrose
n=72 participants at risk
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.
|
L-carnitine
n=72 participants at risk
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.
|
|---|---|---|
|
Infections and infestations
Blood culture positive sepsis
|
5.6%
4/72 • Number of events 4 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
12.5%
9/72 • Number of events 9 • Until hospital discharge, generally upto approximately 44 weeks post-menstrual age.
|
Additional Information
Mamta Fuloria
Children's Hospital at Montefiore, Albert Einstein College of Medicine
Phone: 718-904-4105
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place