Kidney Fat in Type 2 Diabetes and the Effects of Ezetimibe

NCT04589351 | Unknown Phase 3

• 2 other identifiers: 160320202020-001155-40
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 2; Diabetic Kidney Disease

Outcome Measures

Primary Outcomes (1)

• Urinary albumin creatinine ratio (UACR)

  Change over 16 weeks of treatment

Secondary Outcomes (1)

• Magnetic resonans estimate of kidney parenchymal triglyceride fraction

  Change over 16 weeks of treatment

Other Outcomes (3)

• Urine metabolomic profile

  Change over 16 weeks of treatment

• Plasma extracellular vesicles

  Change over 16 weeks of treatment

• Urine extracellular vesicles

  Change over 16 weeks of treatment

Study Arms (2)

Ezetimibe

ACTIVE COMPARATOR

One treatment period of 16 weeks with1 capsule of ezetimibe 10mg per day, as add-on to standard care.

Drug: Ezetimibe 10mg

Placebo

PLACEBO COMPARATOR

One treatment period of 16 weeks with 1 capsule of matching placebo per day, as add-on to standard care.

Drug: Placebo

Interventions

Ezetimibe 10mg DRUG

Ezetimibe is a cholesterol absorption inhibitor with marketing approval. The recommended dose as per label is 10mg once a day.

Ezetimibe

Placebo DRUG

Matching placebo

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 40 and ≤ 75 years
• T2D (World Health Organization criteria)
• eGFR ≥ 30ml/min/1,73m2 at screening
• Persistent UACR ≥ 30mg/g (in more than two out of three valid measurements over a minimum of three months)
• LDL \> 1.5mmol/L at screening
• Ability to communicate with the investigator and give informed consent

You may not qualify if:

• Chronic kidney disease primarily ascribed to other causes than diabetes
• Acute kidney disease within 3 months
• No UACR ≥ 3000mg/g in history
• Current or recent (within 3 months) treatment with ezetimibe
• Initiation or adjustment in dosage within 1 month of an angiotensin-converting enzyme (ACE) inhibitor, angiotensin II receptor blocker (ARB), glucagon-like peptide-1 receptor (GLP-1RA) agonists, sodium-glucose cotransporter 2 (SGLT-2) inhibitors or anti-dyslipidemia drug, e.g. a statin
• Any contraindication to MR-examination (e.g. magnetic foreign body that cannot easily be removed from the body prior to the examination, claustrophobia or body size not compatible with the scanner)
• Intolerance to trial drug components
• Any previous major organ transplantation
• Elective major surgery during the trial
• Pregnancy, planned pregnancy or breastfeeding during the trial
• Insufficient contraception during the trial in women of childbearing potential
• Severe alcohol consumption or abuse of recreational drugs
• Moderate to severe liver failure (Child Pugh 7-15)
• Any surgical or medical condition which can be expected to significantly alter the absorption of the trial drug (e.g. major gastrointestinal tract surgery or inflammatory bowel disease)
• Recent (within 30 days or 5-half-lives, whichever is longer) or current participation in another clinical study in which an investigational medicinal product or device has been received

Sponsors & Collaborators

• Steno Diabetes Center Copenhagen: lead
• Glostrup University Hospital, Copenhagen: collaborator
• Aalborg University Hospital: collaborator
• Capital Region's Pharmacy (Region Hovedstadens Apotek), Marielundvej 25, 2730 Herlev, Denmark: collaborator
• Alessia Fornoni, MD PhD, Professor of Medicine, Chief, Katz Family Division of Nephrology and Hypertension: collaborator

Study Sites (1)

Steno Diabetes Center Copenhagen

Gentofte Municipality, Capital Region, 2820, Denmark

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Nephropathies

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To ensure blinding to the trial drug, the tablets containing either ezetimibe or placebo are incapsulated with gelatin and thus identical in appearance (size, color and shape).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study consists of a cross-sectional study and an intervention trial. The latter is a single-center, randomized, double-blinded, placebo-controlled and parallel trial in participants with T2D and non-severe diabetic kidney disease. Trial participants (n=60), by virtue of their baseline examinations (e.g. MR-examinations), also participate in the cross-sectional part of this study where they constitute one of three groups. The other two groups contain controls (n=30) and individuals with T2D and no diabetic kidney disease (n=30).

Study Record Dates

• First Submitted: October 2, 2020
• First Posted: October 19, 2020
• Study Start: October 1, 2020
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2022
• Last Updated: January 18, 2022

Record last verified: 2022-01

Locations

DK (1)