Diabetes Mellitus Type 1
Conditions
Interventions
Trade Name: Victoza
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: LIRAGLUTIDE
CAS Number: 204656-20-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentrat
Sponsors
Medizinische Universität Graz / Endokrinologie und Stoffwechsel
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial 2. Type 1 diabetes mellitus as diagnosed (including I - III): I. history of type 1 diabetes mellitus manifestation with acute hyperglycaemia and ketonuria II. positive results for at least one of four islet antibodies (glutamic acid decarboxy-lase, protein tyrosine phosphatase, zinc transporter 8, or islet cell antibodies) III. residual basal fasting C-peptide of = 0.1 nmol/L 3. Male or female, aged 18 – 64 years (both inclusive) 4. Body mass index (BMI) 19.0 - 28.0 kg/m2 (both inclusive) 5. HbA1c = 80 mmol/mol (= 9.5%) 6. Treated with daily insulin injections or continuous s.c. insulin infusion (CSII) = 1 months. Stable insulin dose as judged by the investigator 7. Able and willing to perform self-monitoring of PG according to the protocol, to keep a diabetes diary and willing to use liraglutide pen-device Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known or suspected hypersensitivity to trial product(s) or related products 2. Use of liraglutide or exenatide within 3 months before screening 3. Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 3 months) 4. Severe hypoglycaemia within 1 month of screening 5. Hypoglycaemia unawareness as judged by the Investigator or hospitalisation for dia-betic ketoacidosis during the previous 2 months 6. Clinically significant abnormal haematology, biochemistry, lipids, or urinalysis or coagulation screening tests, as judged by the investigator and any of the following laboratory safety results: • ASAT, ALAT, lipase, alkaline phosphatase > 2.0 times upper limit of reference range (ULN) • Haemoglobin 50 ng/L 8. Family or personal history of multiple endocrine neoplasia type 2 (MEN2), or family history of medullary thyroid cancer (MTC) 9. Personal history of non-familial medullary thyroid carcinoma 10. History of chronic or idiopathic acute pancreatitis 11. Suffer from or history of a life threatening disease (e.g. cancer except basal cell skin cancer or squamous cell skin cancer), or any clinically significant respiratory, meta-bolic, renal, hepatic, gastrointestinal, endocrinological (with the exception of diabetes mellitus and euthyroid struma), haematological, dermatological, venereal, neurological, psychiatric diseases or other major disorders as judged by the investigator. 12. Cardiac problems defined as decompensated heart failure (New York Heart Associa-tion (NYHA) class III and IV) at any time and/or angina pectoris within the last 12 months prior to screening and/or acute myocardial infarction at any time. 13. Supine blood pressure at screening (after resting for 5 min) outside the range of 90?140 mmHg for systolic or 50?90 mmHg for diastolic (repeated measurement on a second screening Visit allowed to exclude white-coat hypertension). This exclusion criterion also pertains to subjects being on antihypertensives. 14. Clinically significant abnormal ECG at screening, as judged by the investigator. 15. Proliferative retinopathy or maculopathy and/or severe neuropathy, in particular auto-nomic neuropathy, as judged by the investigator. 16. Any disease or condition that, in the opinion of the investigator, would represent an unacceptable risk for the subject’s safety. 17. Subject positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies (or diagnosed with active hepatitis according to local practice). 18. Positive result of the screening test for HIV-1 antibodies, HIV-2 antibodies and/or HIV-1 antigen according to locally used diagnostic testing. 19. History of multiple and/or severe allergies to drugs or foods or a history of severe ana-phylactic reaction. 20. Subject who has donated any blood or plasma in the past month or more than 500 mL within 3 months prior to screening. 21. Surgery or trauma with significant blood loss (more than 500 mL) within the last 3 months prior to screening. 22. Current treatment with systemic (oral or i.v.) corticosteroids, MAO inhibitors, non-selective beta-blockers, growth hormone, herbal products or non-routine vitamins. Fur-thermore, thyroid hormones are not allowed unless the use of these has been stable during the p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of liraglutide as add on to intensive insulin treatment on the change of EGP during a hypoglycaemic clamp in C-peptide positive subjects with type 1 diabetes mellitus;Secondary Objective: To investigate the effect of liraglutide as add on to intensive insulin treatment on Mixed Meal Tolerance Test(MMTT) enriched with Paracetamol: • Change of gastric emptying during a MMTT assessed before firstdosing and after three months of liraglutide treatment compared to placebo • glucagon and C-peptide response after during MMTT enriched with paracetamol before first dosing of liraglutide and after three months treatment Hypoglycaemic Clamp: • the change of peripheral glucose uptake • the area under glucose infusion rate curve • the glucagon response • lactate, free fatty acids and glycerol levels • the counterregulatory hormone levels Clinical 3 months treatment: • the glucagon levels • the change of beta cell function • the HbA1c and fasting plasma glucose (PG) levels • the daily insulin treatment dose • the change in body weight • frequency and type of self-reported hypoglycaemic episodes • the number and function of regulatory T-cells (Tregs) ;Primary end point(s): Area under the curve of endogenous glucose production (AUCEGP) from begin of 5.5 mmol/L period until end of recovery period (4.0 mmol/L), calculated from stable isotope labelled plasma glucose (PG) (labelled PG). ;Timepoint(s) of evaluation of this end point: At the end of each period (Period 1: After 3 months) (Period 2: After 7 months) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.)Mixed Meal Tolerance Test with paracetamol: The following endpoints relate to the MMTT with paracetamol before first dosing and after 3 months of treatment: • Area under the glucose curve above the average baseline glucose value (average of the -5 and 0 min values) from time point 0 until 240 min during MMTT (AUCglu) • Area under the C-peptide concentration curve (AUCC-peptide) from time point 0 until 120 min during MMTT • Area under the C-peptide concentration curve (AUCC-peptide) from time point 0 until 240 min during MMTT • C-peptide concentration at time point 90 min (C-Peptide90) during MMTT • Area under the glucagon curve above the average baseline glucagon value (average of the -5 and 0 min values) from time point 0 until 240 min during MMTT (AUCglucagon) • Mean glucagon and insulin concentration • Gastric emptying calculated from the paracetamol concentrations as the area under the paracetamol concentration curve from time point 0 until 30 min (AUCpara30), time point 0 until 60 min (AUCpara60) time point 0 until 90 min (AUCpara90), from time point 0 until 120 min (AUCpara120), from time point 0 until 180 min (AUCpara180), and from time point 0 until 240 min (AUCpara240). 2.) Hypoglycaemic clamp: The following endpoints relate to the whole period from begin of period 5.5mmol/L until end of recovery period (4.0 mmol/L) • Area under the curve of peripheral glucose uptake (PGU), (AUCPGU) calculated from labelled PG. • AUCGIR, area under the glucose infusion rate curve The following endpoints are derived for each PG level (5.5, 3.5 and 2.5 mmol/L) during the hypoglycaemic clamp, and for the recovery phase (4.0mmol/L): • EGP and PGU • AUCGIR • mean plasma glucagon concentrations; insulin/insulin secretion rate (if as-sessable), C-peptide • mean values of adrenaline, noradrenaline, cortisol, growth hormone • mean values of lactate, free fatty acids and glycerol • time to reach each hypoglycaemic level (5.5, 3.5 and 2.2 mmol/L) • cha | — |
Countries
Austria
Contacts
Public ContactZentrum f. Med. Grundlagenforschung
Medizinische Universität Graz / Endokrinologie und Stoffwechsel
Outcome results
None listed