Effect of Continuous Glucose Monitoring on Hypoglycemia in Adults With Pancreatogenic Diabetes

This study will investigate the effect of continuous glucose monitoring (CGM) (compared to self-monitoring) on hypoglycemia and glycemic control in patients with insulin-treated pancreatogenic diabetes.

Study Overview

• Status: Completed
• Conditions: Pancreatogenic Type 3C Diabetes Mellitus
• Intervention / Treatment: Device: Continuous glucose monitoring

Detailed Description

The use of CGM in people with type 1 or type 2 diabetes receiving multiple daily insulin injections improves glycemic control and reduces time spent in hypoglycemia compared to self-monitoring. These beneficial effects of CGM are likely also present in people with pancreatogenic diabetes but have only been sparsely investigated.

In this study, the investigators, therefore, aim to investigate the effects of CGM (compared to self-monitoring) on hypoglycemia and glycemic control in patients with pancreatogenic diabetes. Patients with chronic pancreatitis and insulin-treated diabetes will be randomized 1:1 to receive 50 days of CGM followed by 50 days of self-monitoring or vice versa. Each study period is preceded by 20 days of masked CGM assessment, which also serves as the washout period between the two study periods. Furthermore, the self-monitoring group will use masked CGM for the last 20 days of the study period to monitor glucose levels for comparison with the unmasked CGM period. Thus, each study period lasts a total of 70 days.

The investigators hypothesize that the use of CGM vs self-monitoring of blood glucose in patients with pancreatogenic diabetes will lead to decreased time spent with a glucose value <3.0 mmol/l and increased time in glycemic range.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9000
    • Department of Gastroenterology, Aalborg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent before any study specific procedures
• Able to read and understand Danish
• Male or female age ≥ 18 ≤ 85 years
• A definitive diagnosis of chronic pancreatitis based on the M-ANNHEIM criteria
• A diagnosis of insulin treated pancreatogenic diabetes based on the World Health Organization criteria for diabetes (HbA1c ≥6.5 % (48 mmol/mol) and/or fasting plasma glucose ≥126 mg/dl (7.0 mmol/l)) >3 months after diagnosis of pancreatitis

Exclusion Criteria:

• Known or suspected abdominal cancer (incl. intestine, pancreas, and the hepato-biliary system)
• Severe pre-existing comorbidities (assessed by investigator upon inclusion)
• Attack of acute on chronic pancreatitis requiring admission within four weeks prior to inclusion
• Use of glucocorticoid medications within four weeks prior to inclusion, with the exception of inhaled glucocorticoids in the treatment of chronic pulmonary diseases.
• Presence of autoimmune antibodies suggestive of type 1 diabetes
• Prior pancreatic surgery (including total pancreatectomy, pancreaticoduodenectomy, distal pancreatectomy, pancreaticojejunostomy, enucleation, or Frey procedure)
• Prior gastric surgery or vagotomy
• Autoimmune pancreatitis

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Continuous glucose monitoring; Participants will monitor their glucose levels using CGM with access to interstitial glucose levels continuously throughout the day. Each study period is preceded by 20 days of masked CGM assessment.	Device: Continuous glucose monitoring; Continuous glucose monitoring for 50 days; Other Names: CGM
No Intervention: Self-monitoring of blood glucose; Participants will monitor their blood glucose levels using a glucometer and a capillary blood sample from finger-pricking. Participants will in addition use masked CGM for the last 20 days of the study period to monitor glucose levels for comparison. Each study period is preceded by 20 days of masked CGM assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time spent with glucose value <3.0 mmol/l (level 2 hypoglycemia)	The difference between CGM and self-monitoring of blood glucose in time spent with glucose value <3.0 mmol/l (level 2 hypoglycemia) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in range (glucose value 3.9 - 10.0 mmol/l)	The difference between CGM and self-monitoring of blood glucose in time in range (glucose value 3.9 - 10.0 mmol/L) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Time below range (glucose <3.9 mmol/L)	The difference between CGM and self-monitoring of blood glucose in time below range (glucose value < 3.9 mmol/L) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Time above range (glucose >10.0 mmol/L)	The difference between CGM and self-monitoring of blood glucose in time above range (glucose value >10.0 mmol/L) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Mean glucose (mmol/L)	The difference between CGM and self-monitoring of blood glucose in mean glucose (mmol/L) measured by CGM.	The last 20 ±2 days of each study period
Mean amplitude of glycemic excursions [MAGE]	The difference between CGM and self-monitoring of blood glucose in mean amplitude of glycemic excursions [MAGE] measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Continuous overall net glycemic action [CONGA]	The difference between CGM and self-monitoring of blood glucose in continuous overall net glycemic action [CONGA] measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Insulin dose (unit)	The difference in the mean insulin dose between CGM and self-monitoring of blood glucose.	The last 20 ±2 days of each study period
Standard deviation (mmol/L)	The difference between CGM and self-monitoring of blood glucose in standard deviation of mean glucose (mmol/L) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Coefficient of variance (%)	The difference between CGM and self-monitoring of blood glucose in coefficient of variance of mean glucose (mmol/L) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Time below range (glucose 3.0-3.8 mmol/L, hypoglycaemia level 1)	The difference between CGM and self-monitoring of blood glucose in time below range (glucose value 3.0-3.8 mmol/L) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Time above range (glucose 10.1-13.9 mmol/L, hyperglycaemia level 1)	The difference between CGM and self-monitoring of blood glucose in time above range (glucose value 10.1-13.9 mmol/L) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Time above range (glucose >13.9 mmol/L, hyperglycaemia level 2)	The difference between CGM and self-monitoring of blood glucose in time above range (glucose value >13.9 mmol/L) measured by CGM.	In period 1, the observation period begins on day 50 ±2 days of the study and ends on day 70 ±2 days. In period 2, the observation period starts on day 120 ±2 days and ends on day 140 ±2 days.
Quality of life (EORTC QLQ-C30)	Difference between CGM and self-monitoring of blood glucose in quality of life assessed by EORTC QLQ-C30 questionnaire. The questionnaire has been validated for assessment of quality of life in patients with chronic pancreatitis and is composed of single-item measures and multi-item scales with scores ranging from 0 to 100 after linear transformation of the raw score. A high score for a functional scale represents a high level of functioning, as does a high score for the global health status, while a high score for the symptom items represents a high level of symptomatology.	At the end of each study period (day 70 ±2 and 140 ±2).
Patient global impression of change score (PGIC)	Difference between CGM and self-monitoring of blood glucose in Patient global impression of change score (PGIC). The PGIC is a self-reported measure used to assess a patient's overall perception of improvement or change in their condition over time. It uses a 7-point scale, ranging from "very much improved" to "very much worse". A score ≤3 means that the condition has improved.	At the end of each study period (day 70 ±2 and 140 ±2).
Hypoglycemia awareness	The difference between CGM and self-monitoring of blood glucose in hypoglycemia awareness assessed by the Clarke Hypoglycemia Awareness Survey. It comprises eight questions characterizing the participant's exposure to episodes of moderate and severe hypoglycemia. It also examines the glycemic threshold for, and symptomatic responses to, hypoglycemia. A score of four or more implies impaired awareness of hypoglycemia.	At the end of each study period (day 70 ±2 and 140 ±2).
HbA1c (mmol/L)	The difference between CGM and self-monitoring of blood glucose in HbA1c mmol/L.	At the end of each study period (day 70 ±2 and 140 ±2).
HbA1c (percentage)	The difference between CGM and self-monitoring of blood glucose in HbA1c (percentage).	At the end of each study period (day 70 ±2 and 140 ±2).

Collaborators and Investigators

• Sponsor: Aalborg University Hospital
• Investigators: Principal Investigator: Søren S Olesen, Professor, Mech-Sense, Department of Gastroenterology, Aalborg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2022
• Primary Completion (Actual): June 5, 2024
• Study Completion (Actual): June 5, 2024

Study Registration Dates

• First Submitted: September 15, 2022
• First Submitted That Met QC Criteria: September 19, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): October 4, 2024
• Last Update Submitted That Met QC Criteria: October 3, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes; Continuous Glucose Monitoring; Digestive System Diseases; Chronic pancreatitis; Pancreatic Diseases
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemia
• Other Study ID Numbers: N-20210064 (Other Identifier: North Denmark Region Committee in Health Research Ethics)

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