Clinical trial NCT05902104: CGM-Assisted Management of PN
Official title: CAMP: CGM-Assisted Management of PN
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Intestinal Failure
Hypoglycemia
Hyperglycemia
Keywords: Intestinal Failure
Parenteral Nutrition
Continuous Glucose Monitoring
Hypoglycemia
Hyperglycemia
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: DexCom, Inc.
First posted: 2023-06-13
Enrollment: 10
Sex: ALL
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Inpatients at Boston Children's Hospital (BCH) with intestinal failure dependent on PN followed by the Home Parenteral Nutrition (HPN) and/or Center for Advanced Intestinal Rehabilitation (CAIR) program at BCH.

Brief summary: The purpose of this study is to learn more about changes in glucose levels in hospitalized infants with intestinal failure receiving parenteral nutrition or PN (nutrients delivered intravenously), as they transition from continuous PN (given 24 hours a day) to cycled PN (given less than 24 hours a day).

There is an increased risk of glucose abnormalities with cycled PN, which can be harmful to infant growth and brain health. Continuous glucose monitors (CGM) will be used to measure interstitial glucose levels (in the tissue under the skin), which are similar to blood glucose levels. CGM is a small, minimally-invasive sensor worn on the thigh, which gives a glucose measurement every 5 minutes, and can help us understand changes in blood sugar levels without having to do a blood draw or fingerstick. CGM will be used during PN cycling for up to 30 days or until hospital discharge. If target GIR cycled PN is not reached following 3 sensor periods (up to 10 days per sensor), the parent/guardian will be approached to accept or decline participation in an optional extension phase. In the extension phase, the primary study will be repeated and CGM monitoring will continue until target GIR cycled PN is reached, up to an additional 3 sensor placements. CGM data will be hidden from the clinical team, there will be no change to routine clinical care. CGM may provide false low glucose readings when the tissue around the sensor is compressed (compression lows), such as when laying on the sensor during sleep. We will generate data during the study to help identify and filter the final dataset to remove likely compression lows.

This study may help us understand how cycled PN affects glucose levels in infants with intestinal failure, which may help other children treated with cycled PN in the future.

Detailed description: The objective of this investigation is to quantify dysglycemia associated with cycled parenteral nutrition (PN) and elevated glucose infusion rates (GIR) in infants with intestinal failure and PN-dependence, leveraging high-frequency continuous glucose monitor (CGM) sensor glucose values in a prospective, observational study.

Intestinal failure is a malabsorptive state which necessitates PN in its most severe form. PN is ideally transitioned from continuous (24 hr/day) to cycled PN (\<24 hr/day), requiring higher glucose infusion rates (GIR) to provide the same nutrition content over a shorter time-period. Patients on cycled PN, especially infants, are vulnerable to dysglycemia (abnormal glucose levels), specifically hyperglycemia during PN infusions (due to inadequate insulin relative to high GIR) and hypoglycemia when PN is cycled off (due to delayed insulin suppression after PN suspension). There is no established pediatric GIR threshold above which the risk of abnormal glucose levels significantly increases.

While current practice relies on intermittent blood glucose checks, continuous glucose monitors (CGM) measure high-frequency glucose profiles via minimally-invasive sensors, and are capable of precisely detecting clinically-actionable trends that may otherwise go unrecognized. The CGM sensor measures interstitial glucose, an accepted proxy for blood glucose in patients \> 2 years old with diabetes or glycemic variability. CGM has been successfully used in infants and can fulfill the need for greater quantitative insight into glucose trends in metabolically and neurologically fragile populations, including infants with intestinal failure.

The investigators hypothesize that during high-GIR, cycled PN: a) trough glucose while PN is suspended is less than normal (statistically defined as 100 mg/dL), and b) average glucose while receiving the target (highest) GIR is greater than normal (statistically defined as 120 mg/dL).

Eligible infants will be identified among hospitalized infants at Boston Children's Hospital and followed by the Home Parenteral Nutrition (HPN) program and the Center for Advanced Intestinal Rehabilitation (CAIR). All enrolled participants will have a Dexcom G6 Pro CGM placed within 1 week prior to the anticipated initiation of PN cycling, and CGM will be worn using blinded mode for up to 30 days until target GIR cycled PN is reached (3 sensors maximum). If target GIR cycled PN is not reached following 3 sensor periods (up to 10 days per sensor), the parent/guardian will be approached to accept or decline participation in an optional extension phase. In the extension phase, the primary study will be repeated and CGM monitoring will continue until target GIR cycled PN is reached, up to an additional 3 sensor placements. No CGM will remain in place at the time of discharge.

The CGM readings will remain blinded to the clinical staff members, no real-time CGM alerts will be provided to the clinical staff. The clinical team will manage PN cycling and clinical blood glucose monitoring as per routine clinical practice. Chart review will occur throughout the study period to abstract necessary information about the participant's medical history and interval clinical events.

An initial CGM data review will be conducted by the research team within 72 hours of each sensor removal. The clinical team will be notified if there were intervals meeting the criteria of sustained sensor readings \< 50 mg/dL for greater than or equal to 15 minutes. The clinical team will be provided with the criteria for notification, the date/time stamps associated with those event(s), and information about interpreting CGM readings. We will provide this limited information to the clinical team because sustained CGM sensor readings \< 50 mg/dL may signify that the participant is at increased risk for hypoglycemia (blood glucose \< 70 mg/dL) on cycled PN. The study protocol does not require any blood glucose measurements or other clinical interventions.

Additionally, CGM may provide false low glucose readings when the tissue around the sensor is compressed (compression lows) such as when laying on the sensor during sleep. During study enrollment, a controlled amount of pressure will be applied to the CGM devices worn by CAMP participants during brief testing periods, which will be used to derive a mathematical model of compression lows in infants. These false low readings will be filtered out of the data for accurate data analysis of true low CGM readings. Specifically, the study team will perform brief tests applying pressure to the CGM device and a force sensor will be used to measure the force being applied to the CGM. Up to 1kg force will be applied to the CGM per attempt. There will be up to 2 attempts to apply force and measure a response per day, 3 days of attempts, 6 attempts total, for no more than 20 minutes per attempt. A successful response is defined as a drop in sensor glucose of at least 15 mg/dL sustained until pressure is released.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of intestinal failure with PN dependence
* Hospitalized at Boston Children's Hospital
* Age: 60 days to 18 months
* Corrected gestational age: greater than or equal to 40 weeks
* Weight: greater than or equal to 4kg
* Likely to proceed to PN cycling within the next month, as assessed by the clinical team

Exclusion Criteria:

* Underlying medical conditions or medications that predispose to hypoglycemia or hyperglycemia (e.g. insulin administration, systemic glucocorticoids, hyperinsulinism, adrenal insufficiency, other metabolic diseases)
* Diffuse skin disease such that placement of a CGM sensor would be unsafe or difficult to secure
* Known history of allergy or severe reaction to the adhesive/tape that is used to secure the CGM
* Diffuse body edema that would limit accuracy of CGM sensor
* Poor peripheral perfusion or use of vasoactive agents that would limit accuracy of CGM sensor
* Use of medications that interfere with CGM accuracy (e.g. Hydroxyurea, acetaminophen at more than a maximum dose of 1 g every 6 hours up to 4 g every 24 hours)
* Enrolled in competing clinical trial
* Ward of the state

Primary outcomes:
measure: Trough glucose while PN is suspended
timeFrame: Through study completion, up to 30 days
measure: Average glucose while receiving the target GIR
timeFrame: Through study completion, up to 30 days
Secondary outcomes:
measure: Measures of dysglycemia
timeFrame: Through study completion, up to 30 days
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
Study officials:
affiliation: Boston Children's Hospital
name: Michael SD Agus, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bendorf K, Friesen CA, Roberts CC. Glucose response to discontinuation of parenteral nutrition in patients less than 3 years of age. JPEN J Parenter Enteral Nutr. 1996 Mar-Apr;20(2):120-2. doi: 10.1177/0148607196020002120.
citation: Beltrand J, Colomb V, Marinier E, Daubrosse C, Alison M, Burcelin R, Cani PD, Chevenne D, Marchal CL. Lower insulin secretory response to glucose induced by artificial nutrition in children: prolonged and total parenteral nutrition. Pediatr Res. 2007 Nov;62(5):624-9. doi: 10.1203/PDR.0b013e3181559d5c.
citation: Austhof SI, DeChicco R, Cresci G, Corrigan ML, Lopez R, Steiger E, Kirby DF. Expediting Transition to Home Parenteral Nutrition With Fast-Track Cycling. JPEN J Parenter Enteral Nutr. 2017 Mar;41(3):446-454. doi: 10.1177/0148607115595620. Epub 2016 Sep 29.
citation: Yanagisawa R, Takeuchi K, Komori K, Fujihara I, Hidaka Y, Morita D, Futatsugi A, Ono T, Hidaka E, Sakashita K, Shiohara M. Hypoglycemia During the Temporary Interruption of Parenteral Nutrition Infusion in Pediatric Hematopoietic Stem Cell Transplantation. JPEN J Parenter Enteral Nutr. 2017 Nov;41(8):1414-1418. doi: 10.1177/0148607116665797. Epub 2016 Aug 23.