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

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

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))

Study Overview

• Status: Completed
• Conditions: T2 Diabetes and Fatty Liver Disease (Non-alcoholic Origin)
• Intervention / Treatment: Drug: placebo; Drug: Omega-3 carboxylic acids; Drug: Dapagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 223
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Göteborg, Sweden
    • Research Site
  • Linkoping, Sweden
    • Research Site
  • Stockholm, Sweden
    • Research Site
  • Uppsala, Sweden
    • Research Site
  • Örebro, Sweden
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Uppsala Clinical Research, Uppsala, Sweden
• Investigators: Principal Investigator: Jan Eriksson, MD, Uppsala University Hospital, Uppsala, SE

Publications and helpful links

General Publications

• Eriksson JW, Lundkvist P, Jansson PA, Johansson L, Kvarnstrom M, Moris L, Miliotis T, Forsberg GB, Riserus U, Lind L, Oscarsson J. Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study. Diabetologia. 2018 Sep;61(9):1923-1934. doi: 10.1007/s00125-018-4675-2. Epub 2018 Jul 3.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: October 29, 2014
• First Submitted That Met QC Criteria: October 29, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Actual): March 17, 2017
• Last Update Submitted That Met QC Criteria: February 9, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: omega-3 carboxylic acid
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: D5883C00004