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

NCT03017352 | Completed Phase 2 DMC

• 1 other identifier: Eudract-nr.: 2016-001365-92
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

Diabetes Mellitus, Type 1; Exenatide; Incretins; GLP-1; Insulin

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c

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

  6 months

Secondary Outcomes (21)

• 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

Study Arms (2)

Intervention

EXPERIMENTAL

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

Drug: Exenatide

Placebo

PLACEBO COMPARATOR

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

Drug: Placebos

Interventions

Exenatide DRUG

Also known as: Byetta

Intervention

Placebos DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Filip Krag Knop: lead
• Steno Diabetes Center Copenhagen: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, Capital Region, 2820, Denmark

Location

Related Publications (2)

• 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.

  PMID: 29950475 BACKGROUND

• 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.

  PMID: 32135138 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD, PhD

Study Record Dates

• First Submitted: January 2, 2017
• First Posted: January 11, 2017
• Study Start: December 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: July 10, 2019

Record last verified: 2019-07

Locations

DK (1)