ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12615000986572

Ethics application status

Approved

Date submitted

27/07/2015

Date registered

22/09/2015

Date last updated

26/09/2017

Type of registration

Prospectively registered

Titles & IDs

Public title

Glucose in Well Babies Study (GLOW): An observational study to determine the glucose profile in healthy babies within the first five postnatal days.

Scientific title

In healthy newborns, what are the blood glucose, lactate, and, ketone concentrations in the first five postnatal days measured by blood samples and by continuous interstitial monitoring.

Secondary ID [1]

Nil

Universal Trial Number (UTN)

Trial acronym

Glucose in Well Babies (GLOW)

Linked study record

Health condition

Health condition(s) or problem(s) studied:

To describe the normal concentrations of blood glucose, lactate and ketones within the first five postnatal days.

Condition category

Condition code

Metabolic and Endocrine

Normal metabolism and endocrine development and function

Reproductive Health and Childbirth

Childbirth and postnatal care

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

The study period is from immediately after birth until the completion of the first five postnatal days.

Blood glucose, lactate and beta-hydroxybutyrate analysis

The first blood sample will be taken from the umbilical cord immediately after birth. All other sampling will be sampled from the babies’ heel just prior to a feed is being initiated, in order to reduce the pain of heel lance. The heel will be warmed, in order to reduce the pain and to aid blood flow. Less than 1 ml (small drop) of blood will be taken.
The blood will be analysed for glucose and lactate using glucose oxidase and lactate oxidase on the portable epoc 'Registered Trademark' analyser (Epocal Inc. Ottawa. Canada). Beta-hydroxybutyrate will be analysed using the hand held StatStrip 'Registered Trademark' meter (Nova Biomedical, Waltham, MA, USA), which uses a beta-hydroxybutyrate dehydrogenase reaction for analysis. The results will be blinded to the researcher processing the blood sample and not available to any of the research team until the completion of the study. Experienced neonatal nurses or nurse practitioners will perform the heel lances.

Timing of the heel-lance blood samples

Day One. (Mirroring routine screening)
Immediately after birth a cord blood sample will be taken.
Heel-lance blood samples will commence at approximately one hour after birth, in accordance with the blood glucose screening protocol at Waikato Hospital, followed by three more samples, at least three to four hours apart.

Days Two to Five. Heel-lance samples will be measured every 8 to 10 hours (a 16 maximum of heel-lances will be performed). It is standard practice for the Newborn Screening Card to be collected on Day 3 after birth. Every attempt will be made to link this heel lance with the study blood sampling.
Continuous glucose monitor

As soon after birth as possible an Ipro2 continuous glucose monitor (Medtronic, Minimed `Registered Trademark', Northridge, USA) will be inserted subcutaneously into the baby’s thigh using the insertion device and remain in place for five days. The sensor will be secured with a transparent dressing.

The Ipro 2 does not prevent any normal activities of daily living. The baby can be bathed with the sensor in place. The sensor and dressing will be removed after five completed days, at time which is convenient to the parents. A Remove ' Registered Trademark' (Smith & Nephew, Inc., St Petersburg, USA) wipe will be used to remove the dressing, in order to decrease the potential discomfort. Following removal of the continuous glucose sensor the skin underneath the sensor will be assessed and cleaned. In the event of the sensor becoming dislodged, we will ask the parents if the sensor can be replaced. If the sensor requires replacement, an addition heel lance blood test will be required 1 to 2 hours after the insertion of the new sensor.

Feeding data

Parents will be encouraged to enter all feeds (breast or bottle) into a commonly used breastfeeding software application (Feed Baby Pro, Penguin Apps, Version 21.0.5, Victoria. Australia) on a small hand held computer device. At the completion of the five-day study period, data will be exported as a CVS file and stored in a secure database, for later analysis. If the parents wish to have a copy of the feeding data, in order to continue using the application on a personal device, we will email the information.

Daily Review

At enrolment each family will receive an individualised plan, which will indicate the time frames in which the research staff will be visiting the baby to perform the blood tests and daily review. A member of the research team will be on call for the parents at all times. In the unlikely event of a baby becoming unwell for any reason, the baby will be assessed and referred for treatment. A clinician, who is not part of the study team, will provide treatment. The principal investigator will also be notified. Any required blood samples will be taken as clinical indicated, independent of the study protocol. All babies will remain in the study, unless the parents request otherwise.

Intervention code [1]

Not applicable

Comparator / control treatment

Not applicable - observational study

Control group

Uncontrolled

Outcomes

Primary outcome [1]

To determine the range and variation of blood glucose concentrations.

Timepoint [1]

within the first five postnatal days.

Primary outcome [2]

To determine the range and variation of interstitial glucose concentrations within the first five postnatal days.

Timepoint [2]

Within the first five postnatal days

Secondary outcome [1]

To determine the incidence of blood glucose concentrations < 2.6mM within the first 48 hours after birth

Timepoint [1]

Within the first 48 hours after birth

Secondary outcome [2]

To determine the range and variation of blood lactate concentrations.

Timepoint [2]

Within the first five postnatal days

Secondary outcome [3]

To determine the range and variation of blood ketone concentrations.

Timepoint [3]

Within the first five postnatal days

Secondary outcome [4]

To determine the differences, if any, between breast-fed and formula fed babies in blood glucose concentrations.

Timepoint [4]

Within the first five postnatal days

Secondary outcome [5]

To determine the differences, if any, between breast-fed and formula fed babies in blood lactate concentrations.

Timepoint [5]

within the first five postnatal days

Secondary outcome [6]

To determine the differences, if any, between breast-fed and formula fed babies in blood ketone concentrations.

Timepoint [6]

Within the first five postnatal days

Eligibility

Key inclusion criteria

Babies who are
1. 37 to 42 weeks’ gestation and assessed as appropriate for gestational age at birth.
2. Appropriate weight for gestational age (birth weight > 10th centime and < 90th centile).
3. Singletons
4. Living within 20 kilometers of Waikato Hospital
5. English-speaking parents

Minimum age

0 Hours

Maximum age

6 Days

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Babies will be excluded who have any of the following
1. Birthweight < 2500g or > 4500 g
2. Apgar score < 7 at five minutes of age
3. Skin conditions preventing the attachment of the continuous glucose monitor
4. Unwell for any reason
5. Major congenital abnormalities or terminal conditions.
6. Born to mothers with an antenatal history of diabetes, hypertension, drug dependency, or using medications, which may affect the newborns blood glucose concentration, e.g. corticosteroids, sodium valproate.
7. Born to mothers with a Body Mass Index < 18.5 or > 30 kg/m2

Study design

Purpose

Natural history

Duration

Longitudinal

Selection

Defined population

Timing

Prospective

Statistical methods / analysis

Power and Sample size

Approximately 5,800 babies are born within the Waikato region each year. Of these babies 30 % are likely to be at risk of hypoglycaemia and therefore excluded from our possible study population, leaving approximately 4060 babies.

To reliably describe the range and variation of blood glucose in healthy term babies within the first five postnatal days, we have also used data from the CHLYD study. Glucose profiles from the 258 term babies within the CHYLD study showed the mean glucose concentration at 12 hours of age were 3.3 mM (SD 0.7). In order to have a 95% level of confidence to detect a difference of 0.17mM in the mean blood glucose concentration, between the at-risk babies within the CHYLD study and the healthy term babies we would need to recruit 50 babies.

However, we expect some families not to complete the study. Allowing for a 25% withdrawal we will need to recruit 63 babies. Due to equipment and staff availability only two babies will be enrolled in GLOW at any time. We aim to start recruiting to GLOW in October 2015 and will complete the data collection phase of the study within a one-year period.

To determine the incidence of neonatal hypoglycaemia within the first 48 hours, using the current definition of 2.6mM. Of the 404 at-risk babies recruited to the CHYLD Study, 258 were term babies and of these babies 240 (56 %) became hypoglycaemic (< 2.6mM). Authors from previous reports have reported the incidence of hypoglycaemia in the healthy newborn population is 15%. Using a two-tailed design with alpha at 0.05 and beta at 0.2 we will therefore need 19 babies for the sample size.

Data Analysis

Categorical variables will be analysed using number and percent. Continuous variables will be analysed to determine the distribution, range, and variance.
Interstitial blood glucose concentration profiles will be examined for episodes of hypoglycaemia, and quantified for frequency, duration, and severity. Each baby will have electronic feeding data, which will be time matched with the interstitial glucose concentrations profiles and examined for feed-related variation using regression analysis, box plots and area under the curve analyses.

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/10/2015

Actual

21/11/2015

Date of last participant enrolment

Anticipated

30/04/2017

Actual

25/08/2017

Date of last data collection

Anticipated

30/06/2017

Actual

31/08/2017

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Waikato Medical Research Foundation

Address [1]

Peter Rothwell Academic Centre
Waikato Hospital
Pembroke Street
Private Bag 3200
Waikato Mail Centre
Hamilton 3240

Country [1]

New Zealand

Primary sponsor type

Hospital

Name

Waikato District Health Board

Address

Corner Selwyn and Pembroke Street
Hamilton
West Hamilton
New Zealand 3204

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

University

Name [1]

Liggins Institute, Auckland University

Address [1]

The University of Auckland
Private Bag 92019
Victoria Street West
Auckland 1142

Country [1]

New Zealand

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Health and Disability Ethics Committee of New Zealand

Ethics committee address [1]

Ministry of Health
Freyberg Building
20 Aitken Street
P O Box 5013
Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

30/07/2015

Approval date [1]

19/08/2015

Ethics approval number [1]

15/NTA/104

Summary

Brief summary

Neonatal hypoglycaemia is important because it is linked with poor neurological outcome.  In recent years, there has been considerable interest in the detection and management of neonatal hypoglycaemia.  Babies who are identified as being at risk are screened using heel-lance blood tests for the first days after birth.  If hypoglycaemia is diagnosed, then treatment is usually provided.  Glucose is the primary cerebral fuel and the aim of treatment is to increase the blood glucose concentration to ensure adequate cerebral energy supply.  

The definition of neonatal hypoglycaemia has caused considerable controversy.  The current accepted definition < 2.6mM has been determined using limited, but the only available data.  However, the normal glucose profile of healthy appropriately grown term newborns has never been reliably described, and it is possible that many babies are being unnecessarily treated.  Babies have been shown to use alternative cerebral fuels, primarily lactate and ketones.  The profiles of blood lactate and ketone blood concentrations in healthy newborns within the first week are also unclear.

We propose a prospective observational cohort study in healthy appropriately grown term newborns to describe the normal glucose, lactate and ketone concentration profiles over the first five postnatal days.  Babies enrolled in the study will be cared for as normal newborns, largely by the parents as they progress from hospital, or birthing centre and home.  Parents to capture data about every feed electronically.  

Analysis of the blood will begin as soon as possible after birth, umbilical cord blood will be sampled for the measurement of glucose, lactate and ketones.  During the first 24 hours, each baby will have three heel-lance blood tests for the measurement of glucose, lactate and ketones.  The timing of these initial blood tests will mirror the current screening protocol for at-risk babies.  Following which, babies will have heel-lances blood tests at 8 to 10 hourly intervals (maximum of 16 blood tests over the 5 day period).  The results of the blood tests will not be available until the study is completed. In addition a continuous interstitial glucose monitor will be placed subcutaneously, into the baby’s thigh and remain in place for the five days.
 
If “neonatal hypoglycaemia” as currently defined is shown to be part of normal metabolic transition, it is likely that current clinical management will significantly change.

Trial website

Trial related presentations / publications

Public notes

Attachments [1]

/AnzctrAttachments/367993-3 Sept GLOW Protocol Version 2..docx

Contacts

Principal investigator

Name

Dr Deborah Harris

Address

Newborn Intensive Care Unit
Waikato Hospital
Private Bag 3200
Hamilton
New Zealand 3204

Country

New Zealand

Phone

+64 21 471 790

Fax

Deborah.Harris@waikatodhb.health.nz

Contact person for public queries

Name

Deborah Harris

Address

Newborn Intensive Care Unit
Waikato Hospital
Private Bag 3200
Hamilton
New Zealand 3204

Country

New Zealand

Phone

+64 21 471 790

Fax

Deborah.Harris@waikatodhb.health.nz

Contact person for scientific queries

Name

Deborah Harris

Address

Newborn Intensive Care Unit
Waikato Hospital
Private Bag 3200
Hamilton
New Zealand 3204

Country

New Zealand

Phone

+64 07 8398899 ex 96750

Fax

+64 07 8398742

Deborah.Harris@waikatodhb.health.nz

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Glucose Profiles in Healthy Term Infants in the First 5 Days: The Glucose in Well Babies (GLOW) Study.	2020	https://dx.doi.org/10.1016/j.jpeds.2020.02.079
Embase	Alternative Cerebral Fuels in the First Five Days in Healthy Term Infants: The Glucose in Well Babies (GLOW) Study.	2021	https://dx.doi.org/10.1016/j.jpeds.2020.12.063

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically