Incretin-based Therapy in Late Preclinical Type 1 Diabetes

The objective of the trial is to study whether daily treatment with liraglutide improves endogenous insulin secretion, postpones progression to overt Type 1 diabetes, and is tolerable and safe in subjects aged 10-30 years, who are positive for multiple islet autoantibodies and have dysglycemia.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Drug: Victoza®; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• Finland
  • Oulu, Finland, 90029
    • University of Oulu and Oulu University Hospital, Dept of Children and Adolescents
  • Tampere, Finland, 33520
    • University of Tampere and Tampere University Hospital
  • Turku, Finland, 20520
    • University of Turku and Turku University Hospital
• Sweden
  • Malmö, Sweden, 205 02
    • Lund University and Skåne University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 10-30 years of age
• positive for at least 2 islet autoantibodies
• glucose intolerance or dysglycemia: impaired glucose tolerance (IGT, 2-hour p-gluc 7.8-11.0mmol/l), or impaired fasting glucose (IFG, fp-gluc 6.1-6.9mmol/l), and/or 10% rise in HbA1c since the last measurement (2 - 12 mo ago), and/or p-gluc at least 11.1mmol/l at 30, 60 or 90 min during OGTT
• not pregnant

Exclusion Criteria:

• allergic to liraglutide or other ingredients of Victoza
• type 1 diabetes
• diabetic ketoacidosis
• previous treatment in the last three months with any antidiabetic medication
• impaired liver or kidney function or on dialysis
• severe heart failure
• severe stomach or gut problem resulting in gastroparesis, or inflammatory bowel disease
• past or current history of pancreatitis
• serum calcitonin value above normal (>50 ng/l or at least 3.4pmol/l)
• presence of any chronic metabolic, hematologic or malignant disease
• obesity BMI at least 30
• pregnant females and females of childbearing potential who are not using adequate contraceptive methods.
• breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liraglutide; Subjects with multiple islet autoantibodies and dysglycemia and aged 10-30 years are treated with Victoza®	Drug: Victoza®; Daily subcutaneous injections with increasing doses up to 1.8 mg per day. Duration of treatment 6 months and thereafter follow-up of 6 months.
Placebo Comparator: Placebo; Subjects with multiple islet autoantibodies and dysglycemia and aged 10-30 years are treated with placebo	Drug: Placebo; Daily subcutaneous injections with increasing doses up to 1.8 mg per day. Duration of treatment 6 months and thereafter follow-up of 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FPIR (1+3min serum insulin level after iv glucose infusion)	First phase insulin response during 10-min IVGTT (intravenous glucose tolerance test)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: serum and urine amylase, serum lipase, serum calcitonin, hypoglycemia	Safety: serum and urine amylase, serum lipase, serum calcitonin, hypoglycemia	12 months
Tolerability	Tolerability: frequency of side effects, hypoglycaemia and gastrointestinal symptoms in particular	12 months
Serum C-peptide AUC	Serum C-peptide area under the curve (AUC) during 2-hour OGTT (oral glucose tolerance test)	12 months

Collaborators and Investigators

• Sponsor: University of Oulu
• Collaborators: Turku University Hospital; Oulu University Hospital; Tampere University Hospital; Skane University Hospital

Publications and helpful links

General Publications

• Kero J, Koskenniemi JJ, Karsikas S, Pokka T, Lou O, Toppari J, Veijola R. INnoVative trial design for testing the Efficacy, Safety and Tolerability of 6-month treatment with incretin-based therapy to prevent type 1 DIAbetes in autoantibody positive participants: A protocol for three parallel double-blind, randomised controlled trials (INVESTDIA). Diabet Med. 2022 Oct;39(10):e14913. doi: 10.1111/dme.14913. Epub 2022 Jul 22.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2016
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: September 7, 2016
• First Submitted That Met QC Criteria: September 12, 2016
• First Posted (Estimate): September 13, 2016

Study Record Updates

• Last Update Posted (Actual): January 25, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Liraglutide; Prevention; Diabetes Type 1; Diabetes, Insulin-Dependent; Preclinical Type 1 Diabetes; GLP-1 Analogue; Dysglycemia
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: LiraAABDG10-30; 2014-004761-25 (EudraCT Number); U1111-1177-0704 (Other Identifier: WHO); 3-SRA-2014-301-M-R (Other Grant/Funding Number: Juvenile Diabetes Research Foundation International)