Continuous Glucose Monitoring in At-Risk Newborns

Neonatal Hypoglycemia Clinical Trial

Official title:

Continuous Glucose Monitoring in At-Risk Newborns: A Feasibility Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04386005
• Other study ID #: 00014068
• Status: Recruiting
• Phase: N/A
• Start date: August 9, 2021
• Est. completion date: July 2024

Study information

• Verified date: August 2023
• Source: Milton S. Hershey Medical Center
• Contact: Jeffrey R. Kaiser, MD, MA
• Phone: 717-531-8413
• Email: jkaiser2[@]pennstatehealth.psu.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hypoglycemia (low blood glucose) is a very common problem in newborns, and has been associated with poor neurodevelopment, cognition, and school performance. At-risk newborns (infants of diabetic mothers [IDM], large [LGA] and small [SGA] for gestational age infants, and late preterm [LPT] infants) undergo a hypoglycemia screening protocol that involves numerous intermittent needle sticks to test glucose levels on bedside glucometers; however, continuous glucose monitoring (CGM, currently not approved for clinical use in babies), via a small sensor placed in the thigh (only 1 needle stick), would likely decrease pain while providing continuous glucose levels. This study will evaluate the feasibility, safety, and precision of CGM in at-risk newborns, and determine if this method would decrease the amount of painful procedures and episodes of hypoglycemia missed by intermittent sampling.

As part of regular medical care, participants will undergo intermittent blood glucose screening with heel sticks as per the current hospital standard of care protocol. Regular medical care involves checking the participant's blood glucose via heel stick every few hours using a bedside glucometer, with another heel stick to confirm low values in the laboratory. If the participant has low values, he/she may be treated with oral glucose gel, feedings of breast milk or formula, or intravenous (IV) fluids in the Neonatal Intensive Care Unit (NICU). This research study involves placing a CGM device in addition to undergoing the current blood glucose screening protocol and treatment.

As soon as possible after birth, a continuous glucose monitoring device (Dexcom G7) will be placed on the participant's thigh by a research team member, and will blindly continuously record glucose levels that will be analyzed after discharge. Everyone who agrees to participate in this study will have placement of this experimental device.

The investigational device will stay in place for the same amount of time that a participant is undergoing blood glucose monitoring as per the current standard of care protocol, for a maximum of 7 days. A participant may need to have his/her blood glucose checked after 7 days for regular medical care (and not for research), because his/her glucose concentrations are still low. Being in the research study will not affect a participant's medical care, and will not affect how long he/she needs blood glucose monitoring or treatment.

A research team member will place and remove the CGM. Nurses will evaluate the site of the device for signs of irritation, infection, bleeding, and any other issues at least 3 times per day. After discharge from the hospital, data will be collected from the participant's medical record and participant's mother's medical record, including the participant's sex and birth weight, blood glucose values, details of feedings, treatments given for low glucose concentrations, and NICU admission data. Data that will be collected from the participant's mother's medical record includes age and race, prenatal data, medical history, and medication use. The participant's parents will be asked to fill out a short survey about their experience with this device when it is removed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: July 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Minute to 2 Weeks

Eligibility

Inclusion Criteria:

• At-risk newborns (<48 hours old, all sexes) admitted to the Newborn Nursery or the NICU who meet any of the below criteria:

1. Infant of a diabetic mother (IDM, pre-existing or gestational diabetes)

2. Large for gestational age (LGA, >90th percentile [sex-specific])

3. Small for gestational age (SGA, <10th percentile [sex-specific])

4. Late preterm (LPT, 34 0/7 to 36 6/7 weeks' gestation)

• Any newborn undergoing routine blood glucose screening in the newborn nursery per the Neonatal Hypoglycemia protocol (includes newborns of mothers taking oral hypoglycemic agents, beta-blocker medications, or systemic steroids within 7 days before delivery; and newborns with clinical manifestations of hypoglycemia)

Exclusion Criteria:

• Birth weight <2kg

• hypoxic-ischemic encephalopathy

• a contraindication to oral feeding

• abnormal skin that will preclude placement of the CGM (e.g., skin on the thigh that is not intact)

• chromosomal abnormalities or severe congenital anomalies identified ante- or postnatally

• infants who are not expected to survive or who are in extremis

• additional risk of immunocompromise, including:

1. Skin infections, such as staphylococcus or streptococcus skin infections and herpes (skin, eye, and mouth disease) infection

2. Skin diseases that add additional risk, such as epidermolysis bullosa, ichthyosis, peeling skin syndrome, and hemangiomas

3. Systemic sepsis, viral syndromes

4. Immune diseases such as severe combined immunodeficiency, cancer, T-cell or B-cell deficiencies, inborn errors of metabolism, chromosomal abnormalities, glycogen storage diseases, genetic diseases

5. Abdominal wall defects

Related Conditions & MeSH terms

• Hypoglycemia
• Neonatal Hypoglycemia

Intervention

Device:
• Continuous Glucose Monitoring Device
The Dexcom G7 Glucose Monitoring System (San Diego, CA) reports continuous interstitial blood glucose concentrations every 5 minutes, does not require calibration, and involves only 1 needle stick to place the sensor. The manufacturer recommends that a single sensor may be used for up to 10 days. The Dexcom G7 system is the only FDA approved CGM system for children (age >2 years).

Locations

Country	Name	City	State
United States	Penn State Health Milton S Hershey Medical Center	Hershey	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	Children's Miracle Network, DexCom, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (13)

Agus MSD, Wypij D, Nadkarni, VM. Tight Glycemic Control in Critically Ill Children. N Engl J Med. 2017 Jun 8;376(23):e48. doi: 10.1056/NEJMc1703642. No abstract available. — View Citation

Anand KJ, Coskun V, Thrivikraman KV, Nemeroff CB, Plotsky PM. Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav. 1999 Jun;66(4):627-37. doi: 10.1016/s0031-9384(98)00338-2. — View Citation

Beardsall K, Vanhaesebrouck S, Ogilvy-Stuart AL, Vanhole C, Palmer CR, van Weissenbruch M, Midgley P, Thompson M, Thio M, Cornette L, Ossuetta I, Iglesias I, Theyskens C, de Jong M, Ahluwalia JS, de Zegher F, Dunger DB. Early insulin therapy in very-low-birth-weight infants. N Engl J Med. 2008 Oct 30;359(18):1873-84. doi: 10.1056/NEJMoa0803725. — View Citation

Committee on Fetus and Newborn; Adamkin DH. Postnatal glucose homeostasis in late-preterm and term infants. Pediatrics. 2011 Mar;127(3):575-9. doi: 10.1542/peds.2010-3851. Epub 2011 Feb 28. — View Citation

Galderisi A, Facchinetti A, Steil GM, Ortiz-Rubio P, Cavallin F, Tamborlane WV, Baraldi E, Cobelli C, Trevisanuto D. Continuous Glucose Monitoring in Very Preterm Infants: A Randomized Controlled Trial. Pediatrics. 2017 Oct;140(4):e20171162. doi: 10.1542/peds.2017-1162. Epub 2017 Sep 15. — View Citation

Harris DL, Battin MR, Weston PJ, Harding JE. Continuous glucose monitoring in newborn babies at risk of hypoglycemia. J Pediatr. 2010 Aug;157(2):198-202.e1. doi: 10.1016/j.jpeds.2010.02.003. Epub 2010 Mar 24. — View Citation

Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr. 2012 Nov;161(5):787-91. doi: 10.1016/j.jpeds.2012.05.022. Epub 2012 Jun 23. — View Citation

Hay WW Jr, Raju TN, Higgins RD, Kalhan SC, Devaskar SU. Knowledge gaps and research needs for understanding and treating neonatal hypoglycemia: workshop report from Eunice Kennedy Shriver National Institute of Child Health and Human Development. J Pediatr. 2009 Nov;155(5):612-7. doi: 10.1016/j.jpeds.2009.06.044. No abstract available. — View Citation

Kaiser JR, Bai S, Gibson N, Holland G, Lin TM, Swearingen CJ, Mehl JK, ElHassan NO. Association Between Transient Newborn Hypoglycemia and Fourth-Grade Achievement Test Proficiency: A Population-Based Study. JAMA Pediatr. 2015 Oct;169(10):913-21. doi: 10.1001/jamapediatrics.2015.1631. — View Citation

Shah R, McKinlay CJD, Harding JE. Neonatal hypoglycemia: continuous glucose monitoring. Curr Opin Pediatr. 2018 Apr;30(2):204-208. doi: 10.1097/MOP.0000000000000592. — View Citation

Stechova K, Cerny M, Brabec R, Ulmannova T, Bartaskova D, Spalova I, Zoban P. Experience with real time continuous glucose monitoring in stabilising fluctuating glycaemia during intensive care of the preterm infant of a diabetic mother. J Matern Fetal Neonatal Med. 2014 Sep;27(13):1389-91. doi: 10.3109/14767058.2013.858686. Epub 2013 Nov 13. — View Citation

Uettwiller F, Chemin A, Bonnemaison E, Favrais G, Saliba E, Labarthe F. Real-time continuous glucose monitoring reduces the duration of hypoglycemia episodes: a randomized trial in very low birth weight neonates. PLoS One. 2015 Jan 15;10(1):e0116255. doi: 10.1371/journal.pone.0116255. eCollection 2015. — View Citation

Wackernagel D, Dube M, Blennow M, Tindberg Y. Continuous subcutaneous glucose monitoring is accurate in term and near-term infants at risk of hypoglycaemia. Acta Paediatr. 2016 Aug;105(8):917-23. doi: 10.1111/apa.13479. Epub 2016 Jun 8. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Agreement of blood glucose concentrations from CGM vs intermittent monitoring	Bland-Altman analysis to evaluate bias and the agreement interval between CGM and intermittent testing	1-7 days
Primary	Likert-scale questionnaire results from parents, nurses, and research team	Feasibility of the CGM device will be evaluated by administering Likert-scale questionnaire results from parents, nurses, and research team. Questionnaires will assess acceptability of using the device by parents, nurses, and researchers; and ease of use, placement, and maintenance of the device.	7 days
Primary	Difference in number of needle sticks with CGM vs intermittent glucose monitoring	The total number of estimated needle sticks with GCM will be compared to the total number of needle sticks from intermittent monitoring, using t-test.	1-7 days
Primary	Difference in number of episodes of hypoglycemia diagnosed with CGM vs intermittent glucose monitoring	Total number of hypoglycemic episodes (blood glucose concentration <40 mg/dL at <4 hours, and <45 mg/dL thereafter) from GCM (episodes lasting >10 minutes) will be compared to the total number of hypoglycemic episodes from intermittent monitoring using t-test. Area under curve analysis will be completed to evaluate duration and severity of hypoglycemic episodes from CGM vs intermittent monitoring, as well as the response to treatment (feedings, dextrose gel, IV dextrose boluses, and dextrose infusions) and timing to normalization of glucose concentrations.	1-7 days
Secondary	Number of participants with adverse outcomes at the device site	Safety of CGM device will be evaluated by examinations for the presence of irritation, infection, cellulitis, bleeding, or other concerns at the device site.	3 times per day for 1-7 days

External Links

•   5. "Births and Natality." National Center for Health Statistics, Centers for Disease Control and Prevention
•   Get Started with Dexcom CGM. Provides information about the Dexcom G6 device