Continuous Glucose Monitoring Alerts, Accuracy, and Patient Outcomes in Adults With Inherited Metabolic Disorders

Continuous Glucose Monitoring Alerts, Accuracy, and Patient Outcomes in Adults With Inherited Metabolic Disorders Prone to Hypoglycemia

The goal of this clinical trial is to learn if a continuous glucose monitor (CGM) with predictive alerts works better than a CGM with standard alerts to prevent low blood sugar (hypoglycemia) in adults with inherited metabolic disorders (IMDs), such as glycogen storage disorders (GSDs) and congenital hyperinsulinism (CH).

The main questions it aims to answer are:

Does a CGM with predictive alerts lower the time spent with low blood sugar compared to a CGM with standard alerts? Do participants feel better and behave differently when using a CGM with predictive alerts? How accurate are the two CGM devices in this group of people? Researchers will compare two CGM devices - Dexcom G7 (with predictive and standard alerts) and Dexcom ONE+ (with standard alerts only) - to see if predictive alerts help reduce low blood sugar episodes and improve quality of life.

Participants will:

Wear each CGM device for 30 days Have a 30-day break between the two devices Check blood sugar levels and record food intake Complete questionnaires about their experience with each device

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Glycogen Storage Disease; Congenital Hyperinsulinism (CHI)
• Intervention / Treatment: Device: Continuous glucose monitor with threshold and predictive alerts (Dexcom G7); Device: Continuous glucose monitor with threshold-only alerts (Dexcom ONE+)

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Padova
    • Padova, Padova, Italy, 35128
      • University Hospital of Padova

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 years or older
• Genetic or biochemical diagnosis of Glycogen Storage Disease (GSD) or Congenital Hyperinsulinism (CH)
• At least one clinical and biochemical follow-up at the hospital outpatient service within the last one or two years
• Ability to sign informed consent and comply with study procedures

Exclusion Criteria:

• Inability to sign informed consent or comply with study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dexcom G7 (Threshold + Predictive Alerts)	Device: Continuous glucose monitor with threshold and predictive alerts (Dexcom G7); The Dexcom G7 is a CE-marked continuous glucose monitoring (CGM) device worn for 30 days. It provides real-time interstitial glucose readings every 5 minutes. The device offers both threshold-based alerts, activated when glucose levels fall below or rise above pre-set values, and predictive alerts, activated when glucose levels are predicted to reach a threshold within 20 minutes. The low glucose alert threshold was set at 70 mg/dL for all participants.
Active Comparator: Dexcom ONE+ (Threshold-Only Alerts)	Device: Continuous glucose monitor with threshold-only alerts (Dexcom ONE+); The Dexcom ONE+ is a CE-marked continuous glucose monitoring (CGM) device worn for 30 days. It provides real-time interstitial glucose readings every 5 minutes. The device offers threshold-based alerts only, activated when glucose levels fall below or rise above pre-set values, without predictive alert functionality. The low glucose alert threshold was set at 70 mg/dL for all participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Below Range (TBR)	Percentage of time spent with interstitial glucose levels below 70 mg/dL, as measured by continuous glucose monitoring (CGM). TBR is reported at two thresholds: TBR1 (54-69 mg/dL) and TBR2 (<54 mg/dL), both expressed as percentage of monitoring time (%), over 30 days for each device. Unit of Measure: % of monitoring time	30 days per device (total study duration: approximately 90 days including washout period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in Range (TIR)	Percentage of time spent with interstitial glucose levels within the target range of 70-140 mg/dL, as measured by CGM over 30 days for each device. Expressed as percentage of monitoring time (%). Unit of Measure: % of monitoring time	Time Frame: 30 days per device
Time Above Range (TAR)	Percentage of time spent with interstitial glucose levels above 140 mg/dL, as measured by CGM over 30 days for each device. Expressed as percentage of monitoring time (%). Unit of Measure: % of monitoring time	Time Frame: 30 days per device
Mean Glucose Level	Mean interstitial glucose levels calculated over 24 hours and during nighttime (00:00-07:00), as measured by CGM over 30 days for each device. Unit of Measure: mg/dL	Time Frame: 30 days per device
Sensor Accuracy - median absolute relative difference (MARD)	Accuracy of CGM readings compared to capillary blood glucose reference values (Accu-Check Instant, Roche), expressed as Median Absolute Relative Difference (MARD). Capillary and CGM values matched within a ±5-minute time window. Unit of Measure: %	30 days per device
Dietary Intake Assessment	Total daily energy intake measured during each device wear period Unit of Measure: kcal/day Total daily macronutrient intake measured during each device wear period Unit of Measure: grams/day Daily uncooked cornstarch intake measured during each device wear period Unit of Measure: grams/day All dietary intakes were assessed by 7-day food diary analyzed with Metadieta® software (Meteda Srl, Italy), completed during CGM monitoring and reviewed by an experienced metabolic dietitian.	7 days per device
Hypoglycemia Fear and Protective Behaviors Assessment	Assessed using the Hypoglycemia Fear Survey (HFS), comprising two subscales: Worry (HFS-W) and Behavior (HFS-B). Each item scored 0-4; total range 0-132; higher scores indicate greater fear of hypoglycemia and more behaviors engaged to avoid hypoglycemic episodes. Unit of Measure: Score (0-132)	baseline and after 30 days per device
Hypoglycemia Awareness Assessment	Assessed using the Clarke Hypoglycemia Awareness Questionnaire (CHAQ), comprising 8 items on hypoglycemia awareness and recognition. Range 0-7; scores ≥4 indicate impaired awareness of hypoglycemia; higher scores indicate worse hypoglycemia awareness. Unit of Measure: Score (0-7)	baseline and after 30 days per device
Sleep Quality Assessment	assessed using the Pittsburgh Sleep Quality Index (PSQI), a self-report questionnaire assessing sleep quality and disturbances over the previous month. Global score ranges from 0 to 21; scores >5 indicate poor sleep quality; higher scores indicate worse sleep quality. Unit of Measure: Score (0-21)	Baseline and after 30 days per device
Health-Related Quality of Life Assessment	Assessed using the 12-Item Short Form Health Survey (SF-12), yielding Physical Component Summary (PCS) and Mental Component Summary (MCS) standardized scores. Higher scores indicate better quality of life. Unit of Measure: Standardized score for Italian population	Baseline and after 30 days per device
Body Mass Index (BMI)	Height measured at baseline; weight measured at the start and end of each CGM period using a calibrated mechanical scale (Seca 700). BMI calculated as weight (kg)/height² (m²), interpreted according to WHO classification: <18.5 underweight; 18.5-25 healthy weight; 25-30 overweight; >30 obesity. Unit of Measure: kg/m²	Baseline and after 30 days per device

Collaborators and Investigators

• Sponsor: University Hospital Padova
• Collaborators: University of Padova

Publications and helpful links

General Publications

• Gugelmo G, Maines E, Boscari F, Lenzini L, Fadini GP, Burlina A, Avogaro A, Vitturi N. Continuous glucose monitoring in patients with inherited metabolic disorders at risk for Hypoglycemia and Nutritional implications. Rev Endocr Metab Disord. 2024 Oct;25(5):897-910. doi: 10.1007/s11154-024-09903-y. Epub 2024 Oct 1.
• Rossi A, Venema A, Haarsma P, Feldbrugge L, Burghard R, Rodriguez-Buritica D, Parenti G, Oosterveer MH, Derks TGJ. A Prospective Study on Continuous Glucose Monitoring in Glycogen Storage Disease Type Ia: Toward Glycemic Targets. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3612-e3623. doi: 10.1210/clinem/dgac411.
• Overduin RJ, Venema A, Lubout CMA, Fokkert-Wilts MJ, De Boer F, Schreuder AB, Rossi A, Derks TGJ. Continuous glucose monitoring metrics in people with liver glycogen storage disease and idiopathic ketotic hypoglycemia: A single-center, retrospective, observational study. Mol Genet Metab. 2024 Sep-Oct;143(1-2):108573. doi: 10.1016/j.ymgme.2024.108573. Epub 2024 Aug 30.
• Peeks F, Hoogeveen IJ, Feldbrugge RL, Burghard R, de Boer F, Fokkert-Wilts MJ, van der Klauw MM, Oosterveer MH, Derks TGJ. A retrospective in-depth analysis of continuous glucose monitoring datasets for patients with hepatic glycogen storage disease: Recommended outcome parameters for glucose management. J Inherit Metab Dis. 2021 Sep;44(5):1136-1150. doi: 10.1002/jimd.12383. Epub 2021 May 5.
• Ferreira CR, Rahman S, Keller M, Zschocke J; ICIMD Advisory Group. An international classification of inherited metabolic disorders (ICIMD). J Inherit Metab Dis. 2021 Jan;44(1):164-177. doi: 10.1002/jimd.12348.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2025
• Primary Completion (Actual): July 31, 2025
• Study Completion (Actual): September 30, 2025

Study Registration Dates

• First Submitted: May 15, 2026
• First Submitted That Met QC Criteria: May 21, 2026
• First Posted (Actual): May 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 21, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Digestive System Diseases; Infant, Newborn, Diseases; Glucose Metabolism Disorders; Pancreatic Diseases; Hyperinsulinism; Carbohydrate Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hypoglycemia; Glycogen Storage Disease; Congenital Hyperinsulinism
• Other Study ID Numbers: CET 6104/AO/24, URC AOP3544

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No