NCT03648554

Researching an Effect of GLP-1 Agonist on Liver STeatosis (REALIST)

A Multicentre Controlled and Randomized Study Assessing the Effect of Dulaglutide add-on to Dietary Reinforcement Versus Dietary Reinforcement Alone in Patients With Type 2 Diabetes and Carriers of a Non-alcoholic Steatohepatitis

• Status: Unknown
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 93 (estimated)
• Sponsor: Central Hospital, Nancy, France · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

GLP-1 analogues represent new treatments in diabetes that cause weight loss. Their effect on NASH in humans is unknown. A decrease in Alanine Aminotransferase (ALT) has been reported in pooled Exenatide/Placebo and Liraglutide/Placebo studies. More recently, LEAN study has shown that Liraglutide will result in improvements in liver histology in patients with NASH. It should be of high interest to investigate the effect of another GLP-1 Agonist as effective as Liraglutide, i.e. Dulaglutide in NASH. Dulaglutide is one of the five GLP-1 receptor agonists approved for type 2 diabetes mellitus (T2DM). It is an effective treatment because it is dosed once-weekly, provides HbA1c reduction similar to Liraglutide, weight reduction similar to Exenatide, and has an adverse effect profile similar to other GLP-1 receptor agonists. Reduction in body weight was observed in patients treated with Dulaglutide, irrespective of nausea and/or vomiting.The search for a direct effect of Dulaglutide on liver fat overload in patients with type2 diabetes is required before considering the effectiveness of this treatment in NASH in diabetic populations. No current GLP-1 study has been designed with a control group with the same weight loss than as in the treatment group. Primary objective: The investigators aim to study the effect of Dulaglutide 1.5 mg (TRULICITY®) add-on to dietary reinforcement after 52 weeks of treatment, on the improvement of liver histology compared to dietary reinforcement alone in patients with type 2 diabetes and carriers of non-alcoholic steatohepatitis. Secondary objectives: * After 52 weeks of treatment, to assess the effect of dulaglutide (TRULICITY®) add-on to dietary reinforcement on Fibrosis score, Transaminase levels, body composition as measured by dual energy X-ray absorptiometry, lipid profile, glycemic control and weight. The effect of the treatment will also be assessed on quality of life. * At 24 weeks after completion of the treatment, to assess the sustainability of dulaglutide (TRULICITY®) treatment add-on to dietary reinforcement on ALT and AST rates as well as on weight.

Detailed description

This is a multicentre, open, prospective, randomized, controlled dietary reinforcement study. * Treatment Group: dulaglutide (TRULICITY®) subcutaneous administration, one weekly injection, in a dose of 1.5 mg of dulaglutide in combinaison with reinforced dietary monitoring as same as control group. * Control group: reinforced dietary monitoring with frequent dietary consultations, based on AHA recommendations: All patients are monitored in the same way for dietary reinforcement. The study will be conducted over the course of 80 weeks in 3 periods (13 visits): * Period I: Run-in phase of 4 weeks * Period II: Treatment phase of 52 weeks * Period III: Follow-up phase of 24 weeks. The patient must return to the study centre to assess whether the response to treatment is time-dependent.

Conditions

• Diabetes Mellitus, Type 2
• NASH - Nonalcoholic Steatohepatitis

Interventions

Type	Name	Description
DRUG	dulaglutide (TRULICITY®) 1.5 mg	dulaglutide (TRULICITY®) 1.5 mg subcutaneous administration, one weekly injection over 52 weeks of treatment
OTHER	reinforced dietary monitoring	moderate caloric restriction individually adjusted according to the ideal weight and activity level, encouraging regular physical activity (about 30 minutes per day or 150-200 min per week)

Timeline

• Start date: 2019-09-01
• Primary completion: 2023-09-30
• Completion: 2024-03-30
• First posted: 2018-08-27
• Last updated: 2019-06-25

Locations

9 sites across 1 country: France