Clinical trial NCT03017352: Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases
Official title: Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetic Cases: A Randomised, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 1
Keywords: Diabetes Mellitus, Type 1
Exenatide
Incretins
GLP-1
Insulin
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: Steno Diabetes Center Copenhagen
First posted: 2017-01-11
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in HbA1c
timeFrame: 6 months
Secondary outcomes:
measure: adverse events (including hypoglycaemic episodes)
timeFrame: 6 months
measure: changes in insulin dosage
timeFrame: 6 months
measure: changes in body weight
timeFrame: 6 months
measure: changes in BMI
timeFrame: 6 months
measure: changes in body composition
timeFrame: 6 months
measure: changes in body composition
timeFrame: 6 months
measure: changes in body composition
timeFrame: 6 months
measure: changes in fasting plasma glucose
timeFrame: 6 months
measure: changes in post prandial plasma glucose
timeFrame: 6 months
measure: changes in fasting plasma levels of C-peptide
timeFrame: 6 months
measure: Quality of life self reported
timeFrame: 6 months
measure: Treatment satisfaction
timeFrame: 6 months
measure: Treatment satisfaction
timeFrame: 6 months
measure: dietary patterns
timeFrame: 6 months
measure: HDL (High Density Lipoprotein)
timeFrame: 6 months
measure: LDL (Low Density Lipoprotein)
timeFrame: 6 months
measure: VLDL (Very Low Density Lipoprotein)
timeFrame: 6 months
measure: total cholesterol
timeFrame: 6 months
measure: triglycerides
timeFrame: 6 months
measure: proBNP (Pro-Brain Natriuretic Peptide)
timeFrame: 6 months
measure: hsCRP (High-Sensitivity C-Reactive Protein)
timeFrame: 6 months
Other outcomes:
Locations:
city: Gentofte
country: Denmark
facility: Steno Diabetes Center Copenhagen
state: Capital Region
Study officials:
References:
citation: Johansen NJ, Dejgaard TF, Lund A, Vilsboll T, Andersen HU, Knop FK. Protocol for Meal-time Administration of Exenatide for Glycaemic Control in Type 1 Diabetes Cases (The MAG1C trial): a randomised, double-blinded, placebo-controlled trial. BMJ Open. 2018 Jun 27;8(6):e021861. doi: 10.1136/bmjopen-2018-021861.
citation: Johansen NJ, Dejgaard TF, Lund A, Schluntz C, Frandsen CS, Forman JL, Wewer Albrechtsen NJ, Holst JJ, Pedersen-Bjergaard U, Madsbad S, Vilsboll T, Andersen HU, Knop FK. Efficacy and safety of meal-time administration of short-acting exenatide for glycaemic control in type 1 diabetes (MAG1C): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020 Apr;8(4):313-324. doi: 10.1016/S2213-8587(20)30030-9. Epub 2020 Mar 2.