Continuous Glucose Monitoring and Cerebral Oxygenation in Preterm Infants (Glucolight)

November 20, 2020 updated by: Alfonso Galderisi, University Hospital Padova

Impact of Continuous Glucose Monitoring on Cerebral Oxygenation in Preterm Infants (the Babyglucolight Trial)

Neonatal hypoglicaemia is associated with impaired neurodevelopment outcomes in preterm infants. Thus, hypoglicemic events should be diagnosed and treated promptly. Unfortunately, hypo- and hyperglicaemia management is still controversial.

The investigators aim to assess if a continuous glucose monitor (CGM) impacts on both short-term and long-term neurodevelopment. Primary outcome is the effect of CGM coupled with a control algorithm for glucose infusion on the number of hemodynamic significant events (defined as hypoglycemic events associated with DOT-detectable reduction of brain oxygenation).

It will be enrolled newborns ≤32 weeks gestational age and/or of birthweight ≤1500 g, they will be randomized in two study arms, both of them will wear Medtronic CGM during the first 5 days of life: 1) Blinded group (B): the device monitor will be switched off, glucose infusion rate will be modified according to the daily capillary glucose tests. 2) Unblinded group (UB): the device monitor will be visibile, alarms for hypos/hyper will be active and glucose infusion rate will be modulated according to CGM and PID control algorithm.

Enrolled newborns will also be monitored with near-infrared diffuse optical tomography (DOT) during the first 5 days from enrollment.

Follow-up will be performed at 12, 18, 24 months and 5 years by neurodevleopmental scale (Bailey III until 24 months; Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years).

The estimated numerosity is 60 patients (30 for each arm).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Background - Hypoglycaemia is a very common event during the first week of life, it affects up to 15% of term newborns and it is more frequent in preterm and IUGR (Intrauterine Growth Restriction with birth weight <10th percentile) infants.

Repeated and prolonged hypoglicemic events are associated with impaired neurodevelopment outcomes in preterm infants and should be diagnosed and treated promptly (Tam EWY et al, J Pediatrics 2012; Duvanel et al, J Ped 1999; Lucas et al BMJ; 1988; Filam PM et al, J Pediatr 2006).

Unfortunately, the management of hypo / hyperglycaemias in these groups is still controversial due to the lack of Continuous Glucose Monitoring System's (CGMS) efficacy assessments in the Neonatal Care Intensive Units.

Nevertheless, recent studies indicate that CGMS is reliable and can identify a significant number of hypoglycaemias (<40mg / dl, duration> 30 minutes) which could not be recognized through traditional glycemic monitoring (Pertierra Cortada et al, J Ped 2014; Beardsall et al, Arch Dis Child Fetal&Neonatal Ed 2013).

The reliability of data provided by CGMS were highlighted by Beardsall and colleagues (Beardsall et al, Arch Dis Child Fetal & Neonatal Ed 2013) on a population of newborns with an average birth weight of 1007 gr (SD 0.27) and a gestational age of 28.36 SG (SD 2.26), the study showed a high correlation (0.94) between capillary monitoring data (traditional) and data provided by the CGMS.

However, the effects of these CGMS-based approaches on short and long-term neurodevelopment are still unknown, as well as the real impact of these glycemic variations and the maintenance of euglycemia on cerebral hemodynamics.

Indeed, every treatment proposed in this fragile population must have, as its ultimate aim, the improvement of its neuro-cognitive development in order to be considered effective and useful.

Aim - The study the Investigators are going to conduct is aimed to evaluate if CGM, as driver of therapeutic decisions in preterm newborns (birthweight ≤1500g, gestational age ≤32 weeks) during the first week of life, may be able to improve both short-term and long-term neurodevelopment.

Study design - Randomized Controlled Trial

  • Patients: newborns with GA ≤32weeks and/or BW≤ 1500 g. They will be enrolled within the first 48 hours of life
  • Intervention group: Unblinded CGM + Proportional integrative Derivative algorithm (PID) to adequate daily glucose intake
  • Control group: Blinded CGM with daily glucose intake adequated according to SMBG (=2 blood glucose/day) using standard of care (ESPGHAN) intakes
  • Primary Outcome: to evaluate if the use of CGMS (Continuous glucose monitoring system) combined with an algorithm for glucose infusion reduces the number of hemodynamically significant hypoglycemic events during the first week of life

Matherials and Methods - Continuous glucose sensor (Medtronic guardian) will be applied within 48 hours from birth to the study population on the lateral side of thigh, after parents' consent collection.

All the patients will be randomized to the blinded or unblinded group before the application of CGM. Randomization will be performed using a randomization list electronically generated.

Near-infrared diffuse optical tomography (DOT) will be used for brain monitoring. The instrumentation consists of:

  • A cap, similar to the one we already created and used in a pilot study in this population (Galderisi et al., Neurophotonics 2016)
  • Optical fibers, connected to the instrumentation and inserted into specific holes for optodes placed in the cap
  • An external device containing lasers and detectors, controlled by a portable personal computer

Blinded group: they will wear CGM for 5 days, the alarms and the CGM monitor will be switched off. The daily amount of carbohydrates will be decided according to blood glucose tests (at least 2 per day).

Unblinded group (intervention/open CGM group): they will wear CGM for 5 days, the alarms of CGM will be switched on. The daily intake of carbohydrates will be adapted according to CGM data. In case of reported hypoglicaemia (<47 mg/dl), the data will be confirmed by capillary / catheter blood sampling and it wil be treated with Dextrose 40% gel (200 mg/kg) or 2 mg/kg 10% glucose solution.

Glucose adjustment for values out of the target tight glycemic range (72-144mg/dL) will be decided according to the PID algorithm and performed every 3 hours as suggested by the algorithm.

Numerosity: the estimated numerosity is 60 patients. (30 per arm)

Reasons for study interruption: local and/or systemic complication due to the application of device, transfer of patient to another center of care, withdrawal of consent, death, malfunction of device. Reasons for interruption of monitoring will be specified in the final report.

Risks and benefits analysis - The open CGM is expected to decrease the duration and number of hypoglicemic episodes. Early detection of the hypoglicemic events helps reducing their frequency, while adaptation of carbohydrate intake based on CGM data will prevent further hypoglycemic episodes during the observation period.

In addition, this device permits to reduce the number of blood sampling in the U-CGM group, reducing a painful (heel stick) and potentially dangerous (catheter sampling) procedure.

Even though the risk of local reaction is conceivable, it has never been described in studies conducted in newborns. If a local reaction occurs, the device will be removed and the trial will end for the patient.

Perspective and limits - Although the use of the CGMS in preterm infants has been well described, its efficacy in improving short-term and long-term neurodevelopment has never been established, as well as the connection between glycaemic variations and cerebral activity in this population. Only by achieving this goal the real efficacy and utility of CGMS in this population will be clear.

The study has been designed as a no-profit research project by the Principal Investigators and Collaborators of Neonatal Intensive Care Unit of University of Padua.

Interim assessment: after 20 participants enrolled; subsequent interim assessment have been planned every 20 participants enrolled. Study will be interrupted if >10% difference in primary outcome.

Funding: STARS grant from University of Padova (Italy); Penta Foundation; CARIPARO

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
      • Padua, Italy, 35128
        • Recruiting
        • Neonatal Intensive Care Unit - University Hospital of Padua
        • Contact:
        • Principal Investigator:
          • Alfonso Galderisi, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 hours to 2 days (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • <= 32 weeks gestation
  • birthweight <1500 g

Exclusion Criteria:

  • birthweight <500g
  • congenital pathologies
  • lack of parental consent
  • perinatal maternal infections
  • albinism

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Unblinded CGM
CGM data will be "unblinded", with Hypo/hyperglycemia alarms on. Data will be recorded from CGM every three hours and intervention to adequate glucose intake will be performed to keep glycemia in normal range (72-144mg/dl) if necessary.
Device: Unblinded - CGM (Medtronic Guardian)
Data from device will be readable and alarms on
OTHER: Blinded CGM
Hypo/hyper alarms are off. CGM data will be blinded. Glucose intake will be adequate according to at least 2 capillary glycemic tests per day.
Device: Blinded - CGM (Medtronic Guardian)
Data from device will be blinded and alarms off

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CGMS and brain hemodynamic (posterior areas)
Time Frame: 5 days
Number of hypoglycemic events henomdynamically significant. Hypoglycemic events are defined as any value <72mg/dL (mild hypo) or <47mg/dL (severe hypo). They are classified as "significant" in the presence of a reduction from baseline HbT >=15% (posterior areas)
5 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CGMS and brain hemodynamic (overall)
Time Frame: 5 days
Number of hypoglycemic events henomdynamically significant. Hypoglycemic events are defined as any value <72mg/dL (mild hypo) or <47mg/dL (severe hypo). They are classified as "significant" in the presence of a reduction from baseline HbT >=15% (average of tested areas)
5 days
Long-term neurodevelopment
Time Frame: 24 months
Effect of CGM based intervention on Bayley III performance at 24 months
24 months
Long-term neurodevelopment 2
Time Frame: 12 months
Effect of CGM based intervention on Bayley III performance at 12 months
12 months
Long-term neurodevelopment 3
Time Frame: 18 months
Long-term neurodevelopment on Bayley III performance at 18 months
18 months
Long-term neurodevelopment 4
Time Frame: 36 months
Long-term neurodevelopment on Bayley III performance at 36 months
36 months
Long-term neurodevelopment 4
Time Frame: 50 months
Long-term neurodevelopment on Bayley III performance at 50 months
50 months
CGMS and brain hemodynamic (overall-hyperglycemia)
Time Frame: 5 days
Effect of Hyperglycemia (>144mg/dL and >180mg/dL) on brain hemodynamic
5 days
Intervention and brain hemodynamic
Time Frame: 5 days
effect of intervention on overall brain hemodynamic (baseline vs end of study monitoring DOT)
5 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Padova

Collaborators

University of Padova

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 24, 2020

Primary Completion (ANTICIPATED)

April 30, 2022

Study Completion (ANTICIPATED)

April 30, 2025

Study Registration Dates

First Submitted

April 12, 2020

First Submitted That Met QC Criteria

April 12, 2020

First Posted (ACTUAL)

April 15, 2020

Study Record Updates

Last Update Posted (ACTUAL)

November 25, 2020

Last Update Submitted That Met QC Criteria

November 20, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOP1813

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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