Updating Preventive and Treatment Guidelines for Hypoglycemia in Individuals Living With Type 1 Diabetes

Not Applicable

Not yet recruiting

• Conditions: Type 1 Diabetes

• Registration Number: NCT06683391
• Lead Sponsor: Institut de Recherches Cliniques de Montreal

Brief Summary

The REMODAL trial is a randomized crossover study aiming to update treatment guidelines for mild hypoglycemia in people with Type 1 diabetes using continuous glucose monitoring (CGM) technology. The study will assess whether treating mild hypoglycemia proactively (at a glucose threshold of 5.0 mmol/L) with lower doses of carbohydrate (CHO) is more effective than the traditional reactive approach (treatment at \< 4.0 mmol/L). The goal is to reduce hypoglycemia frequency and improve quality of life, while minimizing caloric intake and rebound hyperglycemia.

Detailed Description

The REMODAL trial explores an individualized, proactive approach to treat mild hypoglycemia in individuals with Type 1 diabetes (T1D) who use CGM. Traditional guidelines, established in the 1980s, recommend the "15g/15min rule" - consuming 15g of CHO every 15 minutes for glucose levels below 4.0 mmol/L. However, these guidelines may no longer be optimal with the advancements in insulin therapies and CGM, which provide real-time glucose data and predict glucose trends.

In this study, 32 adult participants with T1D will receive three interventions to test different amounts and timing of CHO intake under real-life conditions. These are as follows:

1. 8g of CHO at a threshold of 5.0 mmol/L (proactive approach).

2. 16g of CHO at a threshold of 5.0 mmol/L (proactive approach).

3. 16g of CHO at a threshold of \< 4.0 mmol/L (traditional reactive approach).

The primary outcome is the prevention rate of hypoglycemic episodes under each intervention, with additional measures on glucose levels, time spent in hypoglycemia, and rebound hyperglycemia. The study also considers differences in glucose management between multiple daily injections, continuous subcutaneous insulin infusion, and automated insulin delivery systems, which may affect CHO needs. This study hopes to redefine effective hypoglycemia management in the modern era of diabetes care, providing personalized recommendations to improve glycemic control and overall quality of life.

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-06
• Study First Submitted QC: 2024-11-08
• Last Update Submitted: 2024-11-08
• Study First Posted: 2024-11-11
• Last Update Posted: 2024-11-11
• Study Start: 2025-01-06
• Primary Completion: 2026-12-31
• Study Completion: 2027-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 32

Inclusion Criteria

• Adults aged 18 years and older
• Clinical diagnosis of Type 1 diabetes for at least 1 year
• Currently treated with multiple daily insulin injections (MDI), continuous subcutaneous insulin infusion (CSII), or automated insulin delivery (AID) systems
• HbA1c level below 9.0%
• Equal distribution of male and female participants, as well as MDI/CSII and AID users

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Exclusion Criteria

• Gastroparesis
• Significant cardiac rhythm abnormalities
• Clinically significant microvascular complications such as nephropathy (eGFR < 40 ml/min) or severe proliferative retinopathy
• Diagnosis of epilepsy
• Pregnancy or currently breastfeeding
• Severe hypoglycemic episode within 1 month prior to inclusion
• Macrovascular events or uncorrected hypokalemia (K+ < 3.5 mmol/L) within 3 months prior to inclusion
• Anticipated treatment changes during the trial period
• Inability to provide informed consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Percentage of Hypoglycemia Prevention with 16g CHO at 5.0 mmol/L	60 minutes	The primary outcome will measure the percentage of hypoglycemic episodes prevented when participants consume 16 grams of carbohydrate (CHO) at a proactive threshold of 5.0 mmol/L, as indicated by continuous glucose monitoring (CGM) readings. Prevention is defined by the avoidance of any CGM interstitial glucose reading below 4.0 mmol/L following the CHO intake. Measured for each intervention visit within 60 minutes after CHO ingestion.

Secondary Outcome Measures

Name	Time	Method
CGM Interstitial Glucose Levels Post-CHO Intake	10, 15, 20, 30, and 60 minutes	Continuous glucose monitoring will be used to measure interstitial glucose values at intervals of 10, 15, 20, 30, and 60 minutes after the initial CHO intake. This will assess the glucose response and stability following different CHO dosages and thresholds. Measured post-CHO ingestion during each intervention.
Lowest CGM Glucose Value Post-CHO Intake	60 minutes	This outcome will record the lowest CGM glucose reading within 60 minutes following the initial CHO intake for each intervention. This helps determine the effectiveness of the intervention in preventing deep hypoglycemia. Measured within 60 minutes of CHO ingestion during each intervention.
Time Spent in Hypoglycemia Following CHO Intake	60 minutes	The duration, in minutes, spent in hypoglycemia (CGM readings \< 4.0 mmol/L) within 60 minutes after the initial CHO ingestion will be recorded. This will assess how well each intervention prevents prolonged hypoglycemia. Measured within 60 minutes post-CHO ingestion during each intervention.
Percentage of Episodes Corrected by CHO at Specific Time Intervals	10, 15, 20, and 30 minutes	The proportion of hypoglycemic episodes (CGM readings \< 4.0 mmol/L) corrected at 10, 15, 20, and 30 minutes after CHO intake will be measured to evaluate the effectiveness of each CHO intervention. Measured at 10, 15, 20, and 30 minutes after CHO ingestion for each intervention.
Number of Episodes Requiring Additional CHO Treatment	60 minutes	The number of hypoglycemic episodes that require additional CHO intake after the initial dose will be recorded. This assesses whether the initial CHO intake was sufficient to correct hypoglycemia. Measured within 60 minutes post-CHO ingestion during each intervention.
Incidence of Rebound Hyperglycemia (≥ 10.0 mmol/L)	60 minutes	The occurrence of rebound hyperglycemia (CGM reading ≥ 10.0 mmol/L) within 60 minutes following the initial CHO intake will be documented to assess the risk of overcorrection leading to hyperglycemia. Measured within 60 minutes post-CHO ingestion during each intervention.
Total CHO Consumption per Intervention	60 minutes	The cumulative amount of CHO consumed per intervention will be recorded to analyze CHO requirements and efficiency across different intervention arms.
Safety Endpoint - Plasma Glucose and CGM Lag-Time Analysis	5, 10, 15, 20, and 30 minutes	Plasma glucose levels at specified intervals (5, 10, 15, 20, and 30 minutes after CHO intake) will be compared to CGM readings to assess the lag time between plasma and interstitial glucose during hypoglycemia correction. Measured at 5, 10, 15, 20, and 30 minutes post-CHO ingestion for each intervention.

Trial Locations

Locations (1)

Institut de recherches cliniques de Montréal; 🇨🇦 Montreal, Quebec, Canada