Mini-Dose Glucagon to Treat Fasting-induced Hypoglycemia During Ramadan

Study Overview
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Brief Summary
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This study aimed to develop a new approach for the treatment of fasting induced hypoglycemia during ramadan using mini-dose glucagon.

Detailed Description
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This study aimed to understand whether subcutaneously-given mini-dose glucagon (MDG) as an alternative to carbohydrate consumption could avert hypoglycemia or treat it effectively in type 1 diabetes patients who choose to fast during Ramadan in observance of their faith. This treatment method could also avert any negative psychological emotions Muslim people with diabetes may experience by ingesting carbohydrates to control hypoglycemia, thereby breaking their fast. Furthermore, it could improve ability to self-manage fasting, which is an important action for their spiritual and overall wellbeing. There will be two phases included in this study: Pre-crossover Phase: Before starting the crossover trial, a pre-crossover phase will conduct to evaluate hypoglycemia eligibility, frequency and compliance. Crossover Trial Phase: The Crossover Trial Phase will include 20 participants and consist of two (2-weeks) periods. Participants who don't develop any hypoglycemic event or failed to complete both periods will be excluded. Participants will be randomized into two groups: Group A in periods one will use MDG and glucose tablets in period two according to the protocol. Group B in periods one will use glucose tablets and MDG in period two according to the protocol. The primary outcome will be the number of treated fasting induced hypoglycemic events.

Official Title
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Mini-Dose Glucagon to Treat Fasting-induced Hypoglycemia During Ramadan

Conditions
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Fasting Hypoglycemia, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Glucagon Injection
* Other: Glucose Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of T1DM using daily insulin 18.0 to < 65.0 years of age with body mass index 20.0 to <35.0 kg/m2. Having diabetes for ≥2.0 years HbA1c <8.5% Has a smart phone with access to the internet and welling to upload data during the study period. Welling to wear a devise such as continuous glucose monitor ≥6 days/week. Females, not currently known to be pregnant In good general health as evaluated by investigator based on available clinical data Willing to comply to the protocol requirements for the duration of the study Exclusion Criteria: Any history of more than one severe hypoglycemic episode (need assistance by third party) in the past 12 months Any history of more than one episode of diabetic ketoacidosis in the past 12 months Female pregnant or planning to get pregnant. Use of any of the following medications: oral hypoglycemic agents, systemic corticosteroids or beta-blocker, theophylline, beta-adrenergic agonists, 1st generation anticholinergic drugs. History of hypersensitivity to glucagon or severe hypersensitivity reactions (such as angioedema) to any other medications History of uncontrolled hypertension (systolic BP >160 mmHg or diastolic BP >100 mmHg) History of seizure disorder. Presence of any of conditions based on judgment of the investigator that could affect or interfere with the response, absorption, metabolism or execration of glucagon. Currently following any kind of weight-loss diet Currently participation in another clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Interventional Model Description: This is a Randomize Crossover study with a pre-crossover phase and a crossover trial phase, which will include a minimum of 20 participants and consist of two (2-weeks) periods.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glucagon injection<br>Dilute Glucagon (1 mg/ml) | Drug: Glucagon Injection<br>* Participants will be instructed to check their blood glucose (BG) with study meter once they developed hypoglycemia symptoms, their CGM reads below 70 mg/dl, or when the CGM glucose was trending down and the participant intended to treat to prevent hypoglycemia. Participants will be instructed to check BG with meter 3 times and treat the hypoglycemia event using mini-dose glucagon when their BG in range 40-69 mg/dl according a prescribed protocol.<br>|
| Active Comparator: Glucose tablets<br>Dextrose glucose tablets | Other: Glucose Tablets<br>* Participants will be instructed to check their blood glucose (BG) with study meter once they developed hypoglycemia symptoms, their CGM reads below 70 mg/dl, or when the CGM glucose was trending down and the participant intended to treat to prevent hypoglycemia. Participants will be instructed to check BG with meter 3 times and treat the hypoglycemia event using glucose tablets when their BG in range 40-69 mg/dl according a prescribed protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in glucose values from baseline to 30 minute | The change in blood glucose from baseline to 30 minute following treatment of hypoglycemic events | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Events approached 100 mg/dL or increased by 30 mg/dL | During the first hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will record the events approached 100 mg/dL or increased by 30 mg/dL | 60 Minutes | 
| Treatment success from first dose | During the first hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will record the events with blood glucose concentration ≥50 mg/dl 15 minute AND ≥70 mg/dl 30 minute after the initial treatment of a hypoglycemic event | 60 Minutes | 
| Mean Glucose Value, during hypoglycemia event by CGM | During the first hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will calculate the mean glucose value from CGM data | 60 Minutes | 
| Time in Range, during hypoglycemia event by CGM | During the first hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will calculate the percentage of time in range 70-180 mg/dL from CGM data. | 60 Minutes | 
| Time spend below 70 mg/dL, during hypoglycemia event by CGM | During the first hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will calculate the percentage of time <70 mg/dL from CGM data. | 60 Minutes | 
| Minimum Glucose, during hypoglycemia event by CGM | During the first two hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will record the minimum glucose value from CGM data. | 60 Minutes | 
| Maximum Glucose, during hypoglycemia event by CGM | During the first two hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will record the maximum glucose value from CGM data. | 60 Minutes | 
| Mean Glucose Value, during hypoglycemia event by CGM | During the first two hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will calculate the mean glucose value from CGM data | 120 Minutes | 
| Time in Range, during hypoglycemia event by CGM | During the first two hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will calculate the percentage of time in range 70-180 mg/dL from CGM data | 120 Minutes | 
| Time spend below 70 mg/dL, during hypoglycemia event by CGM | During the first two hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will calculate the percentage of time <70 mg/dL from CGM data | 120 Minutes | 
| Minimum Glucose, during hypoglycemia event by CGM | During the first two hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will record the minimum glucose value from CGM data. | 120 Minutes | 
| Maximum Glucose, during hypoglycemia event by CGM | During the first two hour following each hypoglycemic event (BG 50-69 mg/dL), the investigators will record the maximum glucose value from CGM data. | 120 Minutes | 
| The proportion of completion of fasts | The proportion of completion of fasts following treatment of hypoglycemic events | 2 Weeks | 
| Mean Glucose Value, by CGM | During the entire two weeks of intervention/comparator period, the investigators will calculate the mean glucose value from CGM data | 2 Weeks | 
| Time in Range, by CGM | During the entire two weeks of intervention/comparator period, the investigators will calculate the percentage of time in range 70-180 mg/dL from CGM data | 2 Weeks | 
| Time spend below 70 mg/dL, by CGM | During the entire two weeks of intervention/comparator period, the investigators will calculate the percentage of time <70 mg/dL from CGM data | 2 Weeks | 
| Time spend above 180 mg/dL, by CGM | During the entire two weeks of intervention/comparator period, the investigators will calculate the percentage of time >180 mg/dL from CGM data | 2 Weeks | 
| Time spend above 250 mg/dL, by CGM | During the entire two weeks of intervention/comparator period, the investigators will calculate the percentage of time >250 mg/dL from CGM data | 2 Weeks | 
| Coefficient of Variation, by CGM | During the entire two weeks of intervention/comparator period, the investigators will calculate the Coefficient of Variation from CGM data | 2 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 diabetes mellitus, Fasting, Ramadan, Glucagon, Mini-dose, Hypoglycemia