Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases

Study Overview
=================
Brief Summary
-----------------
Patients with type 1 diabetes (T1D) depend on insulin therapy as substitution for the lack of endocrine insulin production due to an autoimmune destruction of beta-cells in the pancreatic inslets. Insulin therapy is based on long lasting basal insulin for controlling fasting plasma glucose, and short lasting mealtime insulin for the postprandial plasma glucose. The long term efficacy of this treatment is measured in glycated haemoglobin A1c (HbA1c) of <7.0% as the treatment goal. Intensive insulin therapy is associated with side effects such as hypoglycaemia, weight gain, and unwanted exaggerated excursions in PPG. This may ultimately affect treatment compliance. The abovementioned problems associated with insulin treatment in T1D can also be seen in insulin-treated patients with type 2 diabetes (T2D). However, in T2D the combination of insulin with glucagon-like peptide-1 (GLP-1) receptor agonist (RA) has proven effective in reducing the weight gain and insulin dose in insulin-treated patients with T2D without exacerbating the risk of hypoglycaemia. Exenatid is a short lasting GLP-1RA approved for treatment in T2D, and the investigators intend to evaluate it in a randomized, controlled trial as add-on therapy to standard insulin therapy for patients with T1D. The investigators hypothesise that the add-on of exenatide to insulin therapy in patients with T1D will reduce insulin requirements, glycaemic excursions and body weight and improve glycaemic control without increasing the risk of hypoglycaemia.

Official Title
-----------------
Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases: A Randomised, Placebo-controlled Trial

Conditions
-----------------
Diabetes Mellitus, Type 1

Intervention / Treatment
-----------------
* Drug: Exenatide
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: T1D according to WHO criteria with duration of ≥1 year Age ≥18 years BMI >22.0 kg/m2 HbA1c >7.5% and <10.0% at visit 0 (screening) Able to count carbohydrates Exclusion Criteria: Insulin pump treatment Hypoglycaemia unawareness (inability to register low blood glucose) Diabetic gastroparesis Compromised kidney function (eGFR <60 ml/min/1.73m2, dialysis or kidney transplantation) Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive) History of acute and/or chronic pancreatitis Subjects with personal or family history of medullary carcinoma or MEN syndrome Inflammatory bowel disease Cancer unless in complete remission for >5 years Proliferative retinopathy Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation Alcohol/drug abuse Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives Pregnant or nursing women Known or suspected hypersensitivity to trial product or related products Receipt of an investigational drug within 30 days prior to visit 0 Simultaneous participation in any other clinical intervention trial

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Exenatide 10 mikrogram, thrice daily, subcutaneous injection prior to main meals, 6 months. | Drug: Exenatide<br> <br> * Other names: Byetta;|
| Placebo Comparator: Placebo<br>Placebo, thrice daily, subcutaneous injection prior to main meals, 6 months. | Drug: Placebos<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Change in HbA1c from baseline to end of study (time 6 months) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events (including hypoglycaemic episodes) |  | 6 months | 
| changes in insulin dosage |  | 6 months | 
| changes in body weight |  | 6 months | 
| changes in BMI |  | 6 months | 
| changes in body composition | DXA scan measuring bonemineral density | 6 months | 
| changes in body composition | DXA scan measuring lean mass | 6 months | 
| changes in body composition | DXA scan measuring fat mass | 6 months | 
| changes in fasting plasma glucose |  | 6 months | 
| changes in post prandial plasma glucose |  | 6 months | 
| changes in fasting plasma levels of C-peptide |  | 6 months | 
| Quality of life self reported | Quality of Life Questionaire | 6 months | 
| Treatment satisfaction | Diabetes treatment satisfactory questionnaire status version | 6 months | 
| Treatment satisfaction | Diabetes treatment satisfactory questionnaire change version | 6 months | 
| dietary patterns | Food frequency questionaire three times during the intervention | 6 months | 
| HDL (High Density Lipoprotein) |  | 6 months | 
| LDL (Low Density Lipoprotein) |  | 6 months | 
| VLDL (Very Low Density Lipoprotein) |  | 6 months | 
| total cholesterol |  | 6 months | 
| triglycerides |  | 6 months | 
| proBNP (Pro-Brain Natriuretic Peptide) |  | 6 months | 
| hsCRP (High-Sensitivity C-Reactive Protein) |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Diabetes Mellitus, Type 1, Exenatide, Incretins, GLP-1, Insulin