Prevention of Mild-to-moderate Hypoglycemia in Type 1 Diabetes

Study Overview
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Brief Summary
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According to guidelines, when a mild-to-moderate hypoglycemia occurs (capillary blood glucose < 4.0 mmol/L), 15-20g of rapidly absorbed carbohydrates should be ingested. Patients should re-test and re-ingest 15-20g carbohydrates every 15 minutes until they recover from hypoglycemia. These recommendations were principally based on two studies conducted in the 80s before the introduction of intensive insulin therapy. In practice, only 32-50% of patients follow the current guidelines. In addition, recent studies suggest that under current intensive insulin therapies, an initial correction with 15g of oral glucose may be insufficient to rapidly correct mild-to-moderate hypoglycemia. With the development and increasing usage of newer glucose monitoring technologies, the community is witnessing a shift in hypoglycemia management, from a reactive to a proactive approach (e.g., prevent imminent episodes rather than treating established episodes).

Official Title
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Towards Prevention of Mild-to-moderate Hypoglycemia in Type 1 Diabetes With Oral Glucose at a Higher Blood Glucose Threshold

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Other: Test to induce a decline in plasma glucose
* Device: Dexcom G6
* Other: Dex4
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years old Clinical diagnosis of type 1 diabetes for at least one year Treatment with multiple daily insulin injections or insulin pump therapy with insulin analogs (rapid, ultra-rapid and basal insulin) A glycated hemoglobin A1c ≤ 10% Exclusion Criteria: Clinically significant microvascular complications: nephropathy (eGFR < 40 ml/min), severe proliferative retinopathy as judged by the investigator, neuropathy (particularly diagnosed gastroparesis) Recent (< 3 months) acute macrovascular event (e.g., acute coronary syndrome or cardiac surgery) Known significant cardiac rhythm abnormality based on investigator's judgement Known significant neurological abnormality (e.g., seizure disorder) based on investigator's judgement Ongoing pregnancy or breastfeeding Severe hypoglycemia episode within 1 month of screening Known uncorrected hypokalemia within the past 3 months (potassium < 3.5 mmol/L)

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: 16g of carbohydrates - Plasma glucose < 4.0 mmol/L<br>16g of carbohydrates will be given when glucose levels are below 4.0 mmol/L (management per guidelines) | Other: Test to induce a decline in plasma glucose<br>* Participants will be admitted at the research center at 7:00 after an overnight fast. A venous catheter will be inserted into an arm vein for blood sampling purposes. A subcutaneous insulin bolus will be administered to bring plasma glucose to the glycemic threshold. Oral carbohydrates (16g) will be given when plasma glucose levels are at the target threshold. Sixty minutes after carbohydrates consumption, a standardized meal will be provided and participants will be discharged 90 minutes after the meal.<br>Device: Dexcom G6<br>* Participants will have to wear a Dexcom G6 during study interventions<br>Other: Dex4<br>* When the glycemic threshold is reach, participants will be given 16g of Dex4<br>Drug: Insulin<br>* A subcutaneous insulin bolus will be given to induce a decline in plasma glucose and reach the glycemic threshold.<br>|
| Active Comparator: 16g of carbohydrates - Plasma glucose ≤ 4.5 mmol/L<br>16g of carbohydrates will be given when glucose levels are equal or below 4.5 mmol/L. | Other: Test to induce a decline in plasma glucose<br>* Participants will be admitted at the research center at 7:00 after an overnight fast. A venous catheter will be inserted into an arm vein for blood sampling purposes. A subcutaneous insulin bolus will be administered to bring plasma glucose to the glycemic threshold. Oral carbohydrates (16g) will be given when plasma glucose levels are at the target threshold. Sixty minutes after carbohydrates consumption, a standardized meal will be provided and participants will be discharged 90 minutes after the meal.<br>Device: Dexcom G6<br>* Participants will have to wear a Dexcom G6 during study interventions<br>Other: Dex4<br>* When the glycemic threshold is reach, participants will be given 16g of Dex4<br>Drug: Insulin<br>* A subcutaneous insulin bolus will be given to induce a decline in plasma glucose and reach the glycemic threshold.<br>|
| Active Comparator: 16g of carbohydrates - Plasma glucose ≤ 5.0 mmol/L<br>16g of carbohydrates will be given when glucose levels are equal or below 5.0 mmol/L. | Other: Test to induce a decline in plasma glucose<br>* Participants will be admitted at the research center at 7:00 after an overnight fast. A venous catheter will be inserted into an arm vein for blood sampling purposes. A subcutaneous insulin bolus will be administered to bring plasma glucose to the glycemic threshold. Oral carbohydrates (16g) will be given when plasma glucose levels are at the target threshold. Sixty minutes after carbohydrates consumption, a standardized meal will be provided and participants will be discharged 90 minutes after the meal.<br>Device: Dexcom G6<br>* Participants will have to wear a Dexcom G6 during study interventions<br>Other: Dex4<br>* When the glycemic threshold is reach, participants will be given 16g of Dex4<br>Drug: Insulin<br>* A subcutaneous insulin bolus will be given to induce a decline in plasma glucose and reach the glycemic threshold.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time spent of glucose levels < 4.0 mmol/L |  | 60 minutes after carbohydrates consumption | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma glucose levels at 5 minutes after carbohydrates consumption |  | 5 minutes after carbohydrates consumption | 
| Plasma glucose levels at 10 minutes after carbohydrates consumption |  | 10 minutes after carbohydrates consumption | 
| Plasma glucose levels at 15 minutes after carbohydrates consumption |  | 15 minutes after carbohydrates consumption | 
| Plasma glucose levels at 20 minutes after carbohydrates consumption |  | 20 minutes after carbohydrates consumption | 
| Plasma glucose levels at 30 minutes after carbohydrates consumption |  | 30 minutes after carbohydrates consumption | 
| Plasma glucose levels at 45 minutes after carbohydrates consumption |  | 45 minutes after carbohydrates consumption | 
| Plasma glucose levels at 60 minutes after carbohydrates consumption |  | 60 minutes after carbohydrates consumption | 
| Lowest plasma glucose level eached after CHO consumption |  | 60 minutes after carbohydrates consumption | 
| Time from CHO consumption to the lowest plasma glucose level reached |  | 60 minutes after carbohydrates consumption | 
| Time from CHO consumption to plasma glucose < 3.5 mmol/L |  | 60 minutes after carbohydrates consumption | 
| Percentage of participants reaching hypoglycemia (< 4.0 mmol/L) after CHO consumption |  | 60 minutes after carbohydrates consumption | 
| Percentage of participants for whom hypoglycemia was corrected at 10 minutes after CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 10 minutes after carbohydrates consumption | 
| Percentage of participants for whom hypoglycemia was corrected at 15 minutes after CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 15 minutes after carbohydrates consumption | 
| Percentage of participants for whom hypoglycemia was corrected at 20 minutes after CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 20 minutes after carbohydrates consumption | 
| Percentage of participants for whom hypoglycemia was corrected at 25 minutes after CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 25 minutes after carbohydrates consumption | 
| Percentage of participants for whom hypoglycemia was corrected at 30 minutes after CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 30 minutes after carbohydrates consumption | 
| Percentage of participants for whom hypoglycemia was corrected at 35 minutes after CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 35 minutes after carbohydrates consumption | 
| Percentage of hypoglycemic events that were corrected at 10 minutes after CHO consumption | Only calculated for events with glucose level < 4.0 mmol/L | 10 minutes after carbohydrates consumption | 
| Percentage of hypoglycemic events that were corrected at 15 minutes after CHO consumption | Only calculated for events with glucose level < 4.0 mmol/L | 15 minutes after carbohydrates consumption | 
| Percentage of hypoglycemic events that were corrected at 20 minutes after CHO consumption | Only calculated for events with glucose level < 4.0 mmol/L | 20 minutes after carbohydrates consumption | 
| Percentage of hypoglycemic events that were corrected at 25 minutes after CHO consumption | Only calculated for events with glucose level < 4.0 mmol/L | 25 minutes after carbohydrates consumption | 
| Percentage of hypoglycemic events that were corrected at 30 minutes after CHO consumption | Only calculated for events with glucose level < 4.0 mmol/L | 30 minutes after carbohydrates consumption | 
| Percentage of hypoglycemic events that were corrected at 35 minutes after CHO consumption | Only calculated for events with glucose level < 4.0 mmol/L | 35 minutes after carbohydrates consumption | 
| Percentage of participants requiring a second treatment with carbohydrates at 20 minutes after the first CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 20 minutes after carbohydrates consumption | 
| Percentage of participants requiring a second treatment with carbohydrates at 40 minutes after the first CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 40 minutes after carbohydrates consumption | 
| Percentage of participants requiring a second treatment with carbohydrates at 60 minutes after the first CHO consumption | Only calculated for participants who will have glucose levels < 4.0 mmol/L | 60 minutes after carbohydrates consumption | 
| Percentage of participants experiencing a rebound hyperglycemia (≥ 10.0 mmol/L) within the first hour following the first carbobydrates consumption |  | 60 minutes after carbohydrates consumption | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoglycemia, Type 1 diabetes, Carbohydrates