A Study to Investigate Effects of Omega-3 Carboxylic Acids and Dapagliflozin on Liver Fat Content in Diabetic Patients

Study Overview
=================
Brief Summary
-----------------
This study is a double-blind randomized, placebo-controlled, parallel-group, 12 week study performed in up to 5 centres in Sweden to assess the effect of Omega-3 carboxylic acids and dapagliflozin on liver fat in patients with Type 2 diabetes with fatty liver (>5.5% as measured with magnetic resonance imaging (MRI))

Official Title
-----------------
A Double-blind Randomized Placebo-controlled, Parallel-group 12 Week Study to Investigate the Effects of Omega-3 Carboxylic Acids and Dapagliflozin on Liver Fat Content in Type 2 Diabetic Patients; EFFECT II

Conditions
-----------------
T2 Diabetes and Fatty Liver Disease (Non-alcoholic Origin)

Intervention / Treatment
-----------------
* Drug: placebo
* Drug: Omega-3 carboxylic acids
* Drug: Dapagliflozin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of informed consent prior to any study specific procedures; Men or women ≥40 years and ≤75 years with suitable veins for cannulation or repeated venepuncture; Have liver fat content as assessed by MRI >5.5%; Diagnosis of Type 2 diabetes since at least 6 months in accordance with WHO criteria. Exclusion Criteria: Any condition when MRI is contraindicated such as, but not limited to, having a pacemaker or claustrophobia; Diagnosis or signs of Type 1 diabetes (e.g. history of positive islet antibodies); Creatinine clearance <60 mL/min at screening (Cockcroft-Gault formula).

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br> | Drug: placebo<br>* Placebo matching to Omega-3 carboxylic acids (olive oil)<br>Drug: Placebo<br>* Placebo matching to dapagliflozin 10 mg<br>|
| Experimental: Omega-3 carboxylic acids 4g / day<br> | Drug: Omega-3 carboxylic acids<br>* 4 g administered as 4 x 1 g capsules<br>|
| Experimental: Dapagliflozin, 10mg / day<br> | Drug: Dapagliflozin<br>* 10 mg administered as 10 mg tablet<br>|
| Experimental: Omega-3 carboxylic acids 4g/day+Dapagliflozin 10mg/day<br> | Drug: Omega-3 carboxylic acids<br>* 4 g administered as 4 x 1 g capsules<br>Drug: Dapagliflozin<br>* 10 mg administered as 10 mg tablet<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in % Liver Fat as Assessed by MRI (Comparison Versus Placebo) | To evaluate the efficacy of the combination therapy (Epanova + Dapagliflozin) when compared to placebo with respect to reduction in liver fat content (%) at the end of 12 weeks of double-blinded treatment. Treatment effect in liver fat reduction (%) was assessed using a mixed linear model with the change from baseline on logarithmic scale as response variable and the logarithm of the baseline value as covariate, treatment as fixed effect, and center as random effect. The treatment effect was then back-transformed to original scale as Geometric mean ratio and presented as percentage change from baseline. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in % Liver Fat (Comparison Between Active Treatment Groups) | To evaluate the relative efficacy of the combination of Epanova and dapagliflozin versus Epanova alone and dapagliflozin alone with respect to reduction in % liver fat at the end of 12 weeks of double-blind treatment. Treatment effect in liver fat reduction (%) was assessed using a mixed linear model with the change from baseline on logarithmic scale as response variable and the logarithm of the baseline value as covariate, treatment as fixed effect, and center as random effect. The treatment effect was then back-transformed to original scale as Geometric mean ratio and presented as percentage change from baseline. | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
omega-3 carboxylic acid