Kidney Fat in Type 2 Diabetes and the Effects of Ezetimibe

Phase 3

• Conditions: Diabetes Mellitus, Type 2; Diabetic Kidney Disease
• Interventions: Drug: Placebo; Drug: Ezetimibe 10mg

• Registration Number: NCT04589351
• Lead Sponsor: Steno Diabetes Center Copenhagen

Brief Summary

In this study, we seek to explore the importance of fat accumulation in the kidneys in relation to diabetic kidney disease (DKD). To do this, we conduct an intervention trial in individuals with type 2 diabetes (T2D) and DKD where we investigate whether the inhibition of intestinal cholesterol absorption with ezetimibe affects albuminuria (a strong risk factor for diabetic complications) and kidney fat accumulation. At the same time and to confirm that kidney fat accumulation is, in fact, abnormal in T2D and DKD, we conduct a cross-sectional study in which we compare kidney fat accumulation in participants at baseline from the intervention trial with a group of individuals with T2D and no DKD and a group of healthy individuals.

Detailed Description

Objective:

1. To compare cross-sectionally the fractions of kidney lipid between controls, individuals with type 2 diabetes and no diabetic kidney disease and individuals with type 2 diabetes and non-severe diabetic kidney disease.

2. To assess by intervention trial whether ezetimibe reduces albuminuria and kidney parenchymal triglyceride fraction in individuals with type 2 diabetes and non-severe diabetic kidney disease.

Design:

1. Cross-sectional study on 30 controls, 30 individuals with type 2 diabetes and no diabetic kidney disease and 60 individuals with type 2 diabetes and non-severe diabetic kidney disease.

2. Single-center, randomized, double-blinded, placebo-controlled and parallel intervention trial in 60 individuals with type 2 diabetes and non-severe diabetic kidney disease Comparative treatment regime: Ezetimibe 10mg per day versus placebo for 16 weeks

Primary endpoint in cross-sectional study:

* Kidney parenchymal triglyceride fraction (estimated by magnetic resonance spectroscopy)

Primary endpoint in intervention trial:

* Urinary albumin creatinine ratio

Secondary endpoint in intervention trial:

• Kidney parenchymal triglyceride fraction (estimated by magnetic resonance spectroscopy)

Main eligibility criteria for control group (cross-sectional study alone):

• Age 40-75 years

• No diabetes mellitus

• No kidney disease or urinary albumin creatinine ratio ≥ 30mg/g

• No contraindication to examination by magnetic resonance

Main eligibility criteria for group of individuals with type 2 diabetes and no diabetic kidney disease (cross-sectional study alone):

• Age 40-75 years

* Type 2 diabetes

* No kidney disease or urinary albumin creatinine ratio ≥ 30mg/g

* No contraindication to examination by magnetic resonance

Main eligibility criteria for group of individuals with type 2 diabetes and non-severe diabetic kidney disease (intervention trial):

• Age 40-75 years

* Type 2 diabetes

* Estimated glomerular filtration rate ≥30ml/min/1,73m2

* Urinary albumin creatinine ratio ≥ 30mg/g

* No contraindication to examination by magnetic resonance

Recruitment

* Controls are recruited via announcements on relevant websites and, if necessary, in newspapers

* Individuals with type 2 diabetes are primarily recruited from the ambulatory at Steno Diabetes Center Copenhagen

Study Timeline

• Study Start: 2020-10-01
• Study First Submitted: 2020-10-02
• Study First Submitted QC: 2020-10-09
• Study First Posted: 2020-10-19
• Status Verified: 2022-01
• Last Update Submitted: 2022-01-14
• Last Update Posted: 2022-01-18
• Primary Completion: 2022-05
• Study Completion: 2022-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	One treatment period of 16 weeks with 1 capsule of matching placebo per day, as add-on to standard care.
Ezetimibe	Ezetimibe 10mg	One treatment period of 16 weeks with1 capsule of ezetimibe 10mg per day, as add-on to standard care.

Primary Outcome Measures

Name	Time	Method
Urinary albumin creatinine ratio (UACR)	Change over 16 weeks of treatment

Secondary Outcome Measures

Name	Time	Method
Magnetic resonans estimate of kidney parenchymal triglyceride fraction	Change over 16 weeks of treatment

Trial Locations

Locations (1)

Steno Diabetes Center Copenhagen; 🇩🇰 Gentofte, Capital Region, Denmark