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Effect of Caffeine on Heart Rate Variability in Newborns

Primary Purpose

Caffeine, Heart Rate Variability, Apnoea of Newborn

Status
Completed
Phase
Not Applicable
Locations
Slovenia
Study Type
Interventional
Intervention
Electrocardiogram
Monitoring of vital functions
Caffeine Citrate 5 mg/kg
Sponsored by
University of Ljubljana
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Caffeine focused on measuring newborn, heart rate variability, caffeine, bed tilt, autonomic nervous system

Eligibility Criteria

undefined - 4 Weeks (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • newborns with apnoea treated with caffeine citrate
  • newborns whose parents have signed the informed consent form

Exclusion Criteria:

  • severe perinatal hypoxia
  • infection
  • liver or renal insufficiency
  • neurological disorders
  • congenital anomalies

Sites / Locations

  • University Medical Centre Ljubljana

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

On Caffeine, maintenance dose

Off caffeine

Arm Description

During receiving maintenance dose of 5 mg/kg caffeine citrate (i.e. 2,5 mg/kg caffeine) in the form of solution, orally or intravenously, Holter electrocardiogram and vital functions were monitored for 40 minutes.

100 hours after caffeine withdrawal Holter electrocardiogram and vital functions were monitored for 40 minutes.

Outcomes

Primary Outcome Measures

Association between caffeine treatment and total power (TP) spectrum of HRV
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. TP (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.
Association between caffeine treatment and high frequency (HF) spectrum of HRV
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. HF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.
Association between caffeine treatment and low frequency (LF) spectrum of HRV
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. LF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.

Secondary Outcome Measures

The correlation between postmenstrual age and total power (TP) spectrum of HRV
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. TP (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.
The correlation between postmenstrual age and high frequency (HF) spectrum of HRV
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. HF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.
The correlation between postmenstrual age and low frequency (LF) spectrum of HRV
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. LF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.
The effect of caffeine on heart rate
Heart rate (beats per minute) was obtained from the segments, recorded by ECG Holter and analysed by the Vision Premier Programme. The selected segments corresponded to the segments HRV parameters were obtained for each bed tilt. The values were compared across the two arms of the study.
The effect of caffeine on breathing frequency
Breathing frequency (breaths per minute) was determined manually by observing the chest movement. The measurement was performed three times while the newborn was sleeping for each bed tilt. The values were compared across the two arms of the study.
The effect of caffeine on arterial oxygen saturation
Arterial oxygen saturation (percent) was performed by a pulse oximeter attached to the right hand. The arterial oxygen saturation value was noted three times with the corresponding breathing frequency while the newborn was sleeping for each bed tilt. The values were compared across the two arms of the study.
The effect of caffeine on body temperature
Body temperature (degree Celsius) was measured by a frontal non-contact infrared thermometer three times for each bed tilt while the newborn was sleeping. The values were compared across the two arms of the study.

Full Information

First Posted
March 20, 2021
Last Updated
April 27, 2021
Sponsor
University of Ljubljana
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1. Study Identification

Unique Protocol Identification Number
NCT04869176
Brief Title
Effect of Caffeine on Heart Rate Variability in Newborns
Official Title
Effect of Caffeine for Apnoea Treatment on Heart Rate Variability in Newborns
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
November 17, 2017 (Actual)
Primary Completion Date
July 31, 2018 (Actual)
Study Completion Date
July 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Ljubljana

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of this study was to evaluate the impact of caffeine treatment, given either orally or intravenously, on heart rate variability in newborns. In addition, the investigators sought for a potential association between caffeine treatment and vital functions.
Detailed Description
At Neonatal Department of University Medical Centre Ljubljana caffeine is used to treat neonatal apnoea. It has known affects on central nervous and cardiovascular systems, but little is known about the impact of caffeine intake on heart rate variability (HRV) in newborns. In this study, the investigators performed measurements on one sample of 25 newborns with apnoea who had been admitted to the Neonatal Department of University Medical Centre Ljubljana and treated with caffeine citrate. The treatment regimen consisted of caffeine citrate of a loading dose of 20 mg/kg of body mass, followed by a daily maintenance dose of 5 mg/kg after 24 hours. The investigators measured parameters of HRV in two situations: while the treatment with caffeine citrate was ongoing and after the treatment was withdrawn. The newborns served as controls. Electrical activity of the heart was measured with a Holter ECG while the newborn was sleeping in supine position, first without a bed tilt and afterwards with a 30° head-up tilt. Simultaneously was evaluated the alertness of the newborn and measured their physiological variables (the breathing frequency, the heart rate, the arterial oxygen saturation, and the body temperature). All parents were given their written consent for their child to participate in the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Caffeine, Heart Rate Variability, Apnoea of Newborn, Newborn
Keywords
newborn, heart rate variability, caffeine, bed tilt, autonomic nervous system

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
On Caffeine, maintenance dose
Arm Type
Experimental
Arm Description
During receiving maintenance dose of 5 mg/kg caffeine citrate (i.e. 2,5 mg/kg caffeine) in the form of solution, orally or intravenously, Holter electrocardiogram and vital functions were monitored for 40 minutes.
Arm Title
Off caffeine
Arm Type
Experimental
Arm Description
100 hours after caffeine withdrawal Holter electrocardiogram and vital functions were monitored for 40 minutes.
Intervention Type
Diagnostic Test
Intervention Name(s)
Electrocardiogram
Other Intervention Name(s)
Holter ECG
Intervention Description
Recording of the electrical activity of the heart during sleep; sleep phases were evaluated. The bed was initially in horizontal position and tilted for 30° head-up after 20 minutes of continuous tracing.
Intervention Type
Diagnostic Test
Intervention Name(s)
Monitoring of vital functions
Intervention Description
Measuring of heart rate, breathing frequency, arterial oxygen saturation and body temperature while recording ECG.
Intervention Type
Drug
Intervention Name(s)
Caffeine Citrate 5 mg/kg
Intervention Description
Caffeine in the form of suspension was given to the newborns.
Primary Outcome Measure Information:
Title
Association between caffeine treatment and total power (TP) spectrum of HRV
Description
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. TP (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.
Time Frame
During Procedure
Title
Association between caffeine treatment and high frequency (HF) spectrum of HRV
Description
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. HF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.
Time Frame
During Procedure
Title
Association between caffeine treatment and low frequency (LF) spectrum of HRV
Description
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. LF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The values were compared across the two arms of the study, using student's t-test for comparisons of normally distributed variables, and Wilcoxon signed-rank test for abnormally distributed data.
Time Frame
During Procedure
Secondary Outcome Measure Information:
Title
The correlation between postmenstrual age and total power (TP) spectrum of HRV
Description
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. TP (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.
Time Frame
During Procedure
Title
The correlation between postmenstrual age and high frequency (HF) spectrum of HRV
Description
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. HF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.
Time Frame
During Procedure
Title
The correlation between postmenstrual age and low frequency (LF) spectrum of HRV
Description
While the newborn was sleeping, the electrical activity of the heart was recorded by using ECG Holter. LF (ms2) was obtained from a suitable 5-minute ECG segment analysed by fast Fourier transform, using the Vision Premier Programme for each bed tilt. The correlation between HRV parameters and postmenstrual age was tested with the Pearson correlation coefficient.
Time Frame
During Procedure
Title
The effect of caffeine on heart rate
Description
Heart rate (beats per minute) was obtained from the segments, recorded by ECG Holter and analysed by the Vision Premier Programme. The selected segments corresponded to the segments HRV parameters were obtained for each bed tilt. The values were compared across the two arms of the study.
Time Frame
During Procedure
Title
The effect of caffeine on breathing frequency
Description
Breathing frequency (breaths per minute) was determined manually by observing the chest movement. The measurement was performed three times while the newborn was sleeping for each bed tilt. The values were compared across the two arms of the study.
Time Frame
During Procedure
Title
The effect of caffeine on arterial oxygen saturation
Description
Arterial oxygen saturation (percent) was performed by a pulse oximeter attached to the right hand. The arterial oxygen saturation value was noted three times with the corresponding breathing frequency while the newborn was sleeping for each bed tilt. The values were compared across the two arms of the study.
Time Frame
During Procedure
Title
The effect of caffeine on body temperature
Description
Body temperature (degree Celsius) was measured by a frontal non-contact infrared thermometer three times for each bed tilt while the newborn was sleeping. The values were compared across the two arms of the study.
Time Frame
During Procedure

10. Eligibility

Sex
All
Maximum Age & Unit of Time
4 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: newborns with apnoea treated with caffeine citrate newborns whose parents have signed the informed consent form Exclusion Criteria: severe perinatal hypoxia infection liver or renal insufficiency neurological disorders congenital anomalies
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Petja Fister, MD, PhD
Organizational Affiliation
University Medical Centre Ljubljana
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Centre Ljubljana
City
Ljubljana
Country
Slovenia

12. IPD Sharing Statement

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Effect of Caffeine on Heart Rate Variability in Newborns

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