Incretin-based therapy in late preclinical type 1 diabetes

INTERVENTION: Trade Name: Victoza Product Name: Victoza Pharmaceutical Form: Solution for injection in pre‐filled pen INN or Proposed INN: LIRAGLUTIDE CAS Number: 204656‐20‐2 Pharmaceutical form of the placebo: Solution for injection in pre‐filled pen Route of administration of the placebo: Subcutaneous use CONDITION: Therapeutic area: Diseases [C] ‐ Hormonal diseases [C19] Type 1 diabetes ; MedDRA version: 18.1 Level: LLT Classification code 10045228 Term: Type I diabetes mellitus System Organ Class: 100000004861 PRIMARY OUTCOME: Main Objective: The main objective of the trial is to study whether daily treatment with liraglutide improves insulin secretion and reverses dysglycemia, and whether liraglutide treatment is tolerable and safe in subjects aged 10‐30 years and having late preclinical type 1 diabetes defined by positivity for multiple betacell specific autoantibodies and dysglycemia. Primary end point(s): Primary end points (1‐3) are:; 1) serum C‐peptide area under the curve (AUC) during 2‐hour OGTT; 2) first phase insulin response (FPIR = 1 + 3 min serum insulin) during 10‐min IVGTT; 3) serum insulin AUC during 10‐min IVGTT Secondary Objective: In addition, the effect of daily liraglutide treatment on immunological variables will be studied. The rate of progression to clinical type 1 diabetes will also be analysed. Timepoint(s) of evaluation of this end point: Timepoints for evaluation of primary end points (1‐3) are:; 1) 1 week before start of treatment and 3, 6, 9 and 12 months after start of treatment; 2) At the start of treatment and 6 mo + 2 wk and 12 mo + 2 wk after start of treatment; 3) At the start of treatment and 6 mo + 2 wk and 12 mo + 2 wk after start of treatment SECONDARY OUTCOME: Secondary end point(s): Secondary end points (1‐8) are: ; 1) safety: serum and urine amylase, serum lipase, serum calcitonin, hypoglycemia ; 2) tolerability: frequency of gastrointestinal side effects (diarrhea, nausea, vomiting) ; 3) plasma glucose variability during continuous glucose monitoring (CGM) ; 4) HbA1c ; 5) proportion of subjects with reversal to normoglycemia ; 6) proportion of subjects diagnosed with type 1 diabetes ; 7) time to the diagnosis to type 1 diabetes from the start of the trial drug ; 8) time to the diagnosis of type 1 diabetes from seroconversion to =2 autoantibodies Timepoint(s) of evaluation of this end point: Timepoints for evaluation of secondary end points (1‐8) are: ; 1) 1 wk before start of treatment, and 6 wk, 3 mo, 6 mo, 9 mo and 12 mo after start of treatment ; 2) 1, 2, 3, 4, 5, 6 wk and 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 mo after start of treatment ; 3) 1 wk before start of treatment, 3, 6, 9 and 12 mo after start of treatment ; 4) 1 wk before start of treatment and 6 wk, 3, 6, 9 and 12 mo after start of treatment ; 5) 3, 6, 9 and 12 months after start of treatment ; 6) 3, 6, 9 and 12 months after start of treatment ; 7) 3, 6, 9 and 12 months after start of treatment ; 8) 3, 6, 9 and 12 months after start of treatment INCLUSION CRITERIA: The subjects are 10‐30 years of age, positive for at least 2 betacell specific autoantibodies, have dysglycemia in OGTT (e.g. impaired glucose tolerance or impaired fasting glucose) or increasing HbA1c (at least 10% increase between two HbA1c measurements or HbA1c at least 5.9% in two measurements), and are not pregnant. Are the trial subjects under 18? yes Number of subjects for this age range: 41 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 41 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range