MAG1C: Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases

Sponsor

Filip Krag Knop (Other)

Overall Status

Completed

CT.gov ID

NCT03017352

Collaborator

Steno Diabetes Center Copenhagen (Other)

108

Enrollment

Location

Arms

Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Exenatide Drug: Placebos	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

108 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2016

Actual Primary Completion Date :

Jun 1, 2019

Actual Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Exenatide 10 mikrogram, thrice daily, subcutaneous injection prior to main meals, 6 months.	Drug: Exenatide Other Names: Byetta
Placebo Comparator: Placebo Placebo, thrice daily, subcutaneous injection prior to main meals, 6 months.	Drug: Placebos

Arm

Intervention/Treatment

Experimental: Intervention

Exenatide 10 mikrogram, thrice daily, subcutaneous injection prior to main meals, 6 months.

Drug: Exenatide

Other Names:

Byetta

Placebo Comparator: Placebo

Placebo, thrice daily, subcutaneous injection prior to main meals, 6 months.

Drug: Placebos

Outcome Measures

Primary Outcome Measures

Change in HbA1c [6 months]
Change in HbA1c from baseline to end of study (time 6 months)

Secondary Outcome Measures

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 [6 months]
DXA scan measuring bonemineral density
changes in body composition [6 months]
DXA scan measuring lean mass
changes in body composition [6 months]
DXA scan measuring fat mass
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 [6 months]
Quality of Life Questionaire
Treatment satisfaction [6 months]
Diabetes treatment satisfactory questionnaire status version
Treatment satisfaction [6 months]
Diabetes treatment satisfactory questionnaire change version
dietary patterns [6 months]
Food frequency questionaire three times during the intervention
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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