Back to resultsPrevention of Mild-to-moderate Hypoglycemia in Type 1 Diabetes (REVERSIBLE)
Primary Purpose
Type 1 Diabetes
Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Test to induce a decline in plasma glucose
Dexcom G6
Dex4
Insulin
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes focused on measuring Hypoglycemia, Type 1 diabetes, Carbohydrates
Eligibility Criteria
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)
Sites / Locations
- Montreal Clinical Research Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
16g of carbohydrates - Plasma glucose < 4.0 mmol/L
16g of carbohydrates - Plasma glucose ≤ 4.5 mmol/L
16g of carbohydrates - Plasma glucose ≤ 5.0 mmol/L
Arm Description
16g of carbohydrates will be given when glucose levels are below 4.0 mmol/L (management per guidelines)
16g of carbohydrates will be given when glucose levels are equal or below 4.5 mmol/L.
16g of carbohydrates will be given when glucose levels are equal or below 5.0 mmol/L.
Outcomes
Primary Outcome Measures
Time spent of glucose levels < 4.0 mmol/L
Secondary Outcome Measures
Plasma glucose levels at 5 minutes after carbohydrates consumption
Plasma glucose levels at 10 minutes after carbohydrates consumption
Plasma glucose levels at 15 minutes after carbohydrates consumption
Plasma glucose levels at 20 minutes after carbohydrates consumption
Plasma glucose levels at 30 minutes after carbohydrates consumption
Plasma glucose levels at 45 minutes after carbohydrates consumption
Plasma glucose levels at 60 minutes after carbohydrates consumption
Lowest plasma glucose level eached after CHO consumption
Time from CHO consumption to the lowest plasma glucose level reached
Time from CHO consumption to plasma glucose < 3.5 mmol/L
Percentage of participants reaching hypoglycemia (< 4.0 mmol/L) after CHO 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
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
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
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
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
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
Percentage of hypoglycemic events that were corrected at 10 minutes after CHO consumption
Only calculated for events with glucose level < 4.0 mmol/L
Percentage of hypoglycemic events that were corrected at 15 minutes after CHO consumption
Only calculated for events with glucose level < 4.0 mmol/L
Percentage of hypoglycemic events that were corrected at 20 minutes after CHO consumption
Only calculated for events with glucose level < 4.0 mmol/L
Percentage of hypoglycemic events that were corrected at 25 minutes after CHO consumption
Only calculated for events with glucose level < 4.0 mmol/L
Percentage of hypoglycemic events that were corrected at 30 minutes after CHO consumption
Only calculated for events with glucose level < 4.0 mmol/L
Percentage of hypoglycemic events that were corrected at 35 minutes after CHO consumption
Only calculated for events with glucose level < 4.0 mmol/L
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
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
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
Percentage of participants experiencing a rebound hyperglycemia (≥ 10.0 mmol/L) within the first hour following the first carbobydrates consumption
Full Information
NCT ID
NCT04876079
First Posted
May 3, 2021
Last Updated
August 29, 2023
Sponsor
Institut de Recherches Cliniques de Montreal
1. Study Identification
Unique Protocol Identification Number
NCT04876079
Brief Title
Prevention of Mild-to-moderate Hypoglycemia in Type 1 Diabetes
Acronym
REVERSIBLE
Official Title
Towards Prevention of Mild-to-moderate Hypoglycemia in Type 1 Diabetes With Oral Glucose at a Higher Blood Glucose Threshold
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
June 1, 2021 (Actual)
Primary Completion Date
June 1, 2023 (Actual)
Study Completion Date
June 30, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institut de Recherches Cliniques de Montreal
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes
Keywords
Hypoglycemia, Type 1 diabetes, Carbohydrates
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
16g of carbohydrates - Plasma glucose < 4.0 mmol/L
Arm Type
Active Comparator
Arm Description
16g of carbohydrates will be given when glucose levels are below 4.0 mmol/L (management per guidelines)
Arm Title
16g of carbohydrates - Plasma glucose ≤ 4.5 mmol/L
Arm Type
Active Comparator
Arm Description
16g of carbohydrates will be given when glucose levels are equal or below 4.5 mmol/L.
Arm Title
16g of carbohydrates - Plasma glucose ≤ 5.0 mmol/L
Arm Type
Active Comparator
Arm Description
16g of carbohydrates will be given when glucose levels are equal or below 5.0 mmol/L.
Intervention Type
Other
Intervention Name(s)
Test to induce a decline in plasma glucose
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Dexcom G6
Intervention Description
Participants will have to wear a Dexcom G6 during study interventions
Intervention Type
Other
Intervention Name(s)
Dex4
Intervention Description
When the glycemic threshold is reach, participants will be given 16g of Dex4
Intervention Type
Drug
Intervention Name(s)
Insulin
Intervention Description
A subcutaneous insulin bolus will be given to induce a decline in plasma glucose and reach the glycemic threshold.
Primary Outcome Measure Information:
Title
Time spent of glucose levels < 4.0 mmol/L
Time Frame
60 minutes after carbohydrates consumption
Secondary Outcome Measure Information:
Title
Plasma glucose levels at 5 minutes after carbohydrates consumption
Time Frame
5 minutes after carbohydrates consumption
Title
Plasma glucose levels at 10 minutes after carbohydrates consumption
Time Frame
10 minutes after carbohydrates consumption
Title
Plasma glucose levels at 15 minutes after carbohydrates consumption
Time Frame
15 minutes after carbohydrates consumption
Title
Plasma glucose levels at 20 minutes after carbohydrates consumption
Time Frame
20 minutes after carbohydrates consumption
Title
Plasma glucose levels at 30 minutes after carbohydrates consumption
Time Frame
30 minutes after carbohydrates consumption
Title
Plasma glucose levels at 45 minutes after carbohydrates consumption
Time Frame
45 minutes after carbohydrates consumption
Title
Plasma glucose levels at 60 minutes after carbohydrates consumption
Time Frame
60 minutes after carbohydrates consumption
Title
Lowest plasma glucose level eached after CHO consumption
Time Frame
60 minutes after carbohydrates consumption
Title
Time from CHO consumption to the lowest plasma glucose level reached
Time Frame
60 minutes after carbohydrates consumption
Title
Time from CHO consumption to plasma glucose < 3.5 mmol/L
Time Frame
60 minutes after carbohydrates consumption
Title
Percentage of participants reaching hypoglycemia (< 4.0 mmol/L) after CHO consumption
Time Frame
60 minutes after carbohydrates consumption
Title
Percentage of participants for whom hypoglycemia was corrected at 10 minutes after CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
10 minutes after carbohydrates consumption
Title
Percentage of participants for whom hypoglycemia was corrected at 15 minutes after CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
15 minutes after carbohydrates consumption
Title
Percentage of participants for whom hypoglycemia was corrected at 20 minutes after CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
20 minutes after carbohydrates consumption
Title
Percentage of participants for whom hypoglycemia was corrected at 25 minutes after CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
25 minutes after carbohydrates consumption
Title
Percentage of participants for whom hypoglycemia was corrected at 30 minutes after CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
30 minutes after carbohydrates consumption
Title
Percentage of participants for whom hypoglycemia was corrected at 35 minutes after CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
35 minutes after carbohydrates consumption
Title
Percentage of hypoglycemic events that were corrected at 10 minutes after CHO consumption
Description
Only calculated for events with glucose level < 4.0 mmol/L
Time Frame
10 minutes after carbohydrates consumption
Title
Percentage of hypoglycemic events that were corrected at 15 minutes after CHO consumption
Description
Only calculated for events with glucose level < 4.0 mmol/L
Time Frame
15 minutes after carbohydrates consumption
Title
Percentage of hypoglycemic events that were corrected at 20 minutes after CHO consumption
Description
Only calculated for events with glucose level < 4.0 mmol/L
Time Frame
20 minutes after carbohydrates consumption
Title
Percentage of hypoglycemic events that were corrected at 25 minutes after CHO consumption
Description
Only calculated for events with glucose level < 4.0 mmol/L
Time Frame
25 minutes after carbohydrates consumption
Title
Percentage of hypoglycemic events that were corrected at 30 minutes after CHO consumption
Description
Only calculated for events with glucose level < 4.0 mmol/L
Time Frame
30 minutes after carbohydrates consumption
Title
Percentage of hypoglycemic events that were corrected at 35 minutes after CHO consumption
Description
Only calculated for events with glucose level < 4.0 mmol/L
Time Frame
35 minutes after carbohydrates consumption
Title
Percentage of participants requiring a second treatment with carbohydrates at 20 minutes after the first CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
20 minutes after carbohydrates consumption
Title
Percentage of participants requiring a second treatment with carbohydrates at 40 minutes after the first CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
40 minutes after carbohydrates consumption
Title
Percentage of participants requiring a second treatment with carbohydrates at 60 minutes after the first CHO consumption
Description
Only calculated for participants who will have glucose levels < 4.0 mmol/L
Time Frame
60 minutes after carbohydrates consumption
Title
Percentage of participants experiencing a rebound hyperglycemia (≥ 10.0 mmol/L) within the first hour following the first carbobydrates consumption
Time Frame
60 minutes after carbohydrates consumption
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rémi Rabasa-Lhoret
Organizational Affiliation
Institut de recherches cliniques de Montréal
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montreal Clinical Research Institute
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1R7
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Prevention of Mild-to-moderate Hypoglycemia in Type 1 Diabetes
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