Treatment of Hypoglycemia in Type 1 Diabetes

Study Overview
=================
Brief Summary
-----------------
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 secondary to the DCCT trial and with insulin formulations with largely different pharmacokinetic profiles from current insulin analogs. Recent studies suggest that with current insulin analogs and intensive therapeutic approach, 15g of carbohydrates may be insufficient to rapidly correct an important proportion of hypoglycemic episodes. It is thus important to determine if the recommended hypoglycemia treatment remains the recommendation.

Official Title
-----------------
Treatment of Mild-to-moderate Hypoglycemia in Adults With Type 1 Diabetes: a Validation Study

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Other: Induced-hypoglycemia test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females ≥ 18 years of old. Clinical diagnosis of type 1 diabetes for at least one year. Treatment with multiple daily insulin injections or insulin pump therapy and using insulin analogs (rapid, ultra-rapid and basal). HbA1c ≤ 10%. Exclusion Criteria: Clinically significant microvascular complications: nephropathy (estimated glomerular filtration rate below 40 ml/min), neuropathy (especially diagnosed gastroparesis) or severe proliferative retinopathy as judged by the investigator. Recent (< 3 months) acute macrovascular event e.g. acute coronary syndrome or cardiac surgery. Known significant cardiac rhythm abnormality based on investigator judgment. Abnormal blood panel and/or anemia (Hb < 100g/L). Ongoing pregnancy or breastfeeding. Severe hypoglycemic episode within 1 month of screening. Known uncorrected hypokalemia (potassium < 3.5 mmol/L; available within the past 3 months).

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 - Glucose levels < 3.0 mmol/L<br>Hypoglycemia treatment with 16g of carbohydrates will be given when glucose levels are below 3.0 mmol/L. | Other: Induced-hypoglycemia test<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 induce hypoglycemia. Oral treatment (16g of carbohydrates or 32g of carbohydrates) will be given when plasma glucose levels are at the target threshold of < 3.0 mmol/L or 3.0-3.5 mmol/L. Hypoglycemia symptoms will be assessed every 10 minutes by the participant using a validated scale starting from the time of insulin bolus until hypoglycemia recovery. One hour after hypoglycemia recovery, a standardized meal will be given.<br>|
| Active Comparator: 16g of carbohydrates - Glucose levels 3.0-3.5 mmol/L<br>Hypoglycemia treatment with 16g of carbohydrates will be given when glucose levels are between 3.0 and 3.5 mmol/L. | Other: Induced-hypoglycemia test<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 induce hypoglycemia. Oral treatment (16g of carbohydrates or 32g of carbohydrates) will be given when plasma glucose levels are at the target threshold of < 3.0 mmol/L or 3.0-3.5 mmol/L. Hypoglycemia symptoms will be assessed every 10 minutes by the participant using a validated scale starting from the time of insulin bolus until hypoglycemia recovery. One hour after hypoglycemia recovery, a standardized meal will be given.<br>|
| Active Comparator: 32g of carbohydrates - Glucose levels < 3.0 mmol/L<br>Hypoglycemia treatment with 32g of carbohydrates will be given when glucose levels are below 3.0 mmol/L | Other: Induced-hypoglycemia test<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 induce hypoglycemia. Oral treatment (16g of carbohydrates or 32g of carbohydrates) will be given when plasma glucose levels are at the target threshold of < 3.0 mmol/L or 3.0-3.5 mmol/L. Hypoglycemia symptoms will be assessed every 10 minutes by the participant using a validated scale starting from the time of insulin bolus until hypoglycemia recovery. One hour after hypoglycemia recovery, a standardized meal will be given.<br>|
| Active Comparator: 32g of carbohydrates - Glucose levels 3.0-3.5 mmol/L<br>Hypoglycemia treatment with 32g of carbohydrates will be given when glucose levels are between 3.0 and 3.5 mmol/L. | Other: Induced-hypoglycemia test<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 induce hypoglycemia. Oral treatment (16g of carbohydrates or 32g of carbohydrates) will be given when plasma glucose levels are at the target threshold of < 3.0 mmol/L or 3.0-3.5 mmol/L. Hypoglycemia symptoms will be assessed every 10 minutes by the participant using a validated scale starting from the time of insulin bolus until hypoglycemia recovery. One hour after hypoglycemia recovery, a standardized meal will be given.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glucose levels 15 minutes after hypoglycemic treatment | Change in glucose levels 15 minutes after hypoglycemic treatment (16g vs. 32g of carbohydrates) when glucose levels at the time of treatment are below 3.0 mmol/L or between 3.0 and 3.5 mmol/L. | 15 minutes after hypoglycemic treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in glucose levels 20 minutes after hypoglycemic treatment | Change in glucose levels 20 minutes after hypoglycemic treatment (16g vs. 32g of carbohydrates) when glucose levels at the time of treatment are below 3.0 mmol/L or between 3.0 and 3.5 mmol/L. | 20 minutes after hypoglycemic treatment | 
| Change in glucose levels 30 minutes after hypoglycemic treatment | Change in glucose levels 30 minutes after hypoglycemic treatment (16g vs. 32g of carbohydrates) when glucose levels at the time of treatment are below 3.0 mmol/L or between 3.0 and 3.5 mmol/L. | 30 minutes after hypoglycemic treatment | 
| Change in glucose levels 45 minutes after hypoglycemic treatment | Change in glucose levels 45 minutes after hypoglycemic treatment (16g vs. 32g of carbohydrates) when glucose levels at the time of treatment are below 3.0 mmol/L or between 3.0 and 3.5 mmol/L. | 45 minutes after hypoglycemic treatment | 
| Change in glucose levels 60 minutes after hypoglycemic treatment | Change in glucose levels 60 minutes after hypoglycemic treatment (16g vs. 32g of carbohydrates) when glucose levels at the time of treatment are below 3.0 mmol/L or between 3.0 and 3.5 mmol/L. | 60 minutes after hypoglycemic treatment | 
| Number of participants with glucose levels above 8.0 mmol/L 1 hour after hypoglycemia correction |  | 60 minutes after hypoglycemia correction | 
| Number of participants with glucose levels above 10.0 mmol/L 1 hour after hypoglycemia correction |  | 60 minutes after hypoglycemia correction | 
| Glucose levels 60 minutes after meal consumption |  | 60 minutes after meal consumption | 
| Glucose levels 90 minutes after meal consumption |  | 90 minutes after meal consumption | 
| Number of patients for whom hypoglycemia was corrected 10 minutes after hypoglycemic treatment |  | 10 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia was corrected 15 minutes after hypoglycemic treatment |  | 15 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia was corrected 20 minutes after hypoglycemic treatment |  | 20 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia was corrected 25 minutes after hypoglycemic treatment |  | 25 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia was corrected 30 minutes after hypoglycemic treatment |  | 30 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia was corrected 35 minutes after hypoglycemic treatment |  | 35 minutes after hypoglycemic treatment | 
| Number of hypoglycemic events corrected 10 minutes after hypoglycemic treatment |  | 10 minutes after hypoglycemic treatment | 
| Number of hypoglycemic events corrected 15 minutes after hypoglycemic treatment |  | 15 minutes after hypoglycemic treatment | 
| Number of hypoglycemic events corrected 20 minutes after hypoglycemic treatment |  | 20 minutes after hypoglycemic treatment | 
| Number of hypoglycemic events corrected 25 minutes after hypoglycemic treatment |  | 25 minutes after hypoglycemic treatment | 
| Number of hypoglycemic events corrected 30 minutes after hypoglycemic treatment |  | 30 minutes after hypoglycemic treatment | 
| Number of hypoglycemic events corrected 35 minutes after hypoglycemic treatment |  | 35 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia symptoms disappeared 10 minutes after hypoglycemic treatment |  | 10 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia symptoms disappeared 15 minutes after hypoglycemic treatment |  | 15 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia symptoms disappeared 20 minutes after hypoglycemic treatment |  | 20 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia symptoms disappeared 25 minutes after hypoglycemic treatment |  | 25 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia symptoms disappeared 30 minutes after hypoglycemic treatment |  | 30 minutes after hypoglycemic treatment | 
| Number of patients for whom hypoglycemia symptoms disappeared 35 minutes after hypoglycemic treatment |  | 35 minutes after hypoglycemic treatment | 
| Number of patients requiring a second treatment 40 minutes after the first hypoglycemic treatment |  | 40 minutes after the first hypoglycemic treatment | 
| Number of patients requiring a second treatment 15 minutes after the first hypoglycemic treatment |  | 15 minutes after the first hypoglycemic treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hypoglycemia, carbohydrates