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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pancreatogenic Type 3C Diabetes Mellitus

Intervention / Treatment
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* Device: Continuous glucose monitoring


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent before any study specific procedures Able to read and understand Danish Male or female age ≥ 18 ≤ 80 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 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous glucose monitoring<br>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<br>* Continuous glucose monitoring for 50 days<br>* Other names: CGM;|
| No Intervention: Self-monitoring of blood glucose<br>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?
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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. | The observation period starts on day 50 after the start of the study period and ends after 20 days (day 70 - end of the study period) | 

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. | The observation period starts on day 50 after the start of the study period and ends after 20 days (day 70 - end of the study period) | 
| 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. | The observation period starts on day 50 after the start of the study period and ends after 20 days (day 70 - end of the study period) | 
| 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. | The observation period starts on day 50 after the start of the study period and ends after 20 days (day 70 - end of the study period) | 
| 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 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. | The observation period starts on day 50 after the start of the study period and ends after 20 days (day 70 - end of the study period) | 
| 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. | The observation period starts on day 50 after the start of the study period and ends after 20 days (day 70 - end of the study period) | 
| Insulin dose (unit) | The difference in the mean insulin dose between CGM and self-monitoring of blood glucose. | From baseline till the end of each study period (70 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 baseline and the end of each study period (day 70). | 
| 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 baseline and the end of each study period (day 70). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic pancreatitis, Pancreatic Diseases, Digestive System Diseases, Diabetes, Continuous Glucose Monitoring