Liraglutide as add-on to Insulin in Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to: Part 1: To investigate how 12 weeks treatment with liraglutide affects glycemic control in poorly controlled patients and how the treatment affects gastric emptying rate during hypoglycemia. Part 2: To investigate how 12 weeks treatment of type 1 diabetic patients with liraglutide affects counterregulatory hormones and cognitive performance during hypoglycemia.

Official Title
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Treatment With Liraglutide as add-on to Insulin in Type 1 Diabetic Patients. Effects on Glycemic Control and Counterregulation and Cognitive Performance During Hypoglycaemia

Conditions
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Diabetes, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Liraglutide
* Drug: Placebo
* Drug: Liraglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-70 years BMI: 18-28 HbA1c ≥ 8 % No residual β-cell function (glucagon test with c-peptide < 60 pM) Caucasian Diagnosed with type 1 diabetes at 5 to 40 years of age (both inclusive). Remission phase must be completed Female participants must use adequate contraception Informed consent Exclusion Criteria: Overt diabetes complications; creatinin > 130 µM, proliferative retinopathy, macroalbuminuria. Autonomic neuropathy (RR-variation </=10 beats/min) and/or Orthostatic hypotension (OH). Anemia, Hb concentration; female <7.0 mmol/l, male<8.0 mmol/l Pregnancy or lactation Epilepsy Use of antiepileptic medication Use of beta blockers Previously apoplexy cerebri. Any use of benzodiazepine within the last month Any use of neuroleptic drugs within the last six months Self-perceived hearing loss Alcohol or drug abuse Allergy to the medication or placebo. Treatment with any medication affecting glucose metabolism. Any disorder which in the investigators opinion could interfere with the safety and results of the trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo + Insulin + Study 2<br>Study 2: Cognitive performance test | Drug: Liraglutide<br>* Subjects randomised to 1.2 mg liraglutide treatment or liraglutide placebo will receive 0.6 mg for 1 weeks followed by 1.2 mg for 11 weeks. At baseline and week 12 study 2 is performed.<br>|
| Experimental: Liraglutide + Insulin + Study 2<br>Study 2: Cognitive performance test | Drug: Placebo<br>* Subjects randomised to 1.2 mg liraglutide treatment or liraglutide placebo will receive 0.6 mg for 1 weeks followed by 1.2 mg for 11 weeks. At baseline and week 12 study 2 is performed.<br>|
| Experimental: Liraglutide + Insulin + Study 1<br>Study 1: Gastric emptying test | Drug: Liraglutide<br>* Subjects randomised to 1.2 mg liraglutide treatment or liraglutide placebo will receive 0.6 mg for 1 weeks followed by 1.2 mg for 11 weeks. At baseline and week 12 study 1 is performed.<br>|
| Placebo Comparator: Placebo + Insulin + Study 1<br>Study 1: Gastric emptying test | Drug: Placebo<br>* Subjects randomised to 1.2 mg liraglutide treatment or liraglutide placebo will receive 0.6 mg for 1 weeks followed by 1.2 mg for 11 weeks. At baseline and week 12 study 1 is performed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c (glycosylated haemoglobin) |  | Week 0, week 12 | 
| Changes from baseline in EEG and cognitive performances |  | week 0, week 12 | 
| Change from baseline in gastric emptying rate |  | week 0, week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in glycemic control (CGM) |  | week 0, week 12 | 
| Change from baseline in total daily insulin dose |  | week 0, week 12 | 
| Changes from baseline in the counterregulatory hormone responses during hypoglycemia |  | week 0, week 12 | 
| Change from baseline in body weight |  | week 0, week 12 | 
| Change from baseline in auditory evoked potentials (AEP) during hypoglycemia |  | week 0, week 12 | 
| Change from baseline in corrected QTc-interval (QTc) during hypoglycemia |  | week 0, week 12 | 
| Change from baseline in hypoglycemic symptom score |  | week 0, week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin, Pharmacologic Actions, Incretins, Diabetes Mellitus, Diabetes Mellitus, Type 1, Glucose Metabolism Disorders, Metabolic Diseases, Cognitive performance, Hypoglycemia, Glucagon-Like Peptide 1, Hypoglycemic Agents, Physiological Effects of Drugs, Hormones