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NCT Number: NCT04865770

A Research Study to Find Out How Semaglutide Works in the Kidneys Compared to Placebo, in People With Type 2 Diabetes and Chronic Kidney Disease (the REMODEL Trial)

We are doing this study to learn more about how semaglutide may help fight chronic kidney disease in people with type 2 diabetes. We are doing this by looking into how semaglutide works in the kidneys.

Participants will either get semaglutide or placebo (a 'dummy' medicine) - which treatment participants get is decided by chance.

Semaglutide is a medicine doctors can prescribe in some countries for the treatment of type 2 diabetes.

Participants will get the study medicine in a pen. Participants will use the pen to inject the medicine into the skin once a week.

The study will last for about 1 year. Participants will have 11 visits to the clinic, and 2 phone visits. Some of the visits could be in different locations.

Study staff will take blood samples at most of these visits. At 9 visits, participants will be asked to bring a sample of their first morning urine. At 4 of the visits participants will have to bring urine that they have collected over the last 24 hours.

The study includes magnetic resonance imaging (MRI) scans of participants' kidneys which is a test that shows a detailed picture of organs and other parts inside the body. The scan will last for 30 minutes, and is free of radiation.

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Key information

Conditions

Diabetes Mellitus, Type 2 Chronic Disease Chronic Kidney Disease Diabetes Mellitus Disease Attributes Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Glucose Metabolism Disorders Kidney Diseases Male Urogenital Diseases Metabolic Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Renal Insufficiency Renal Insufficiency, Chronic Urogenital Diseases Urologic Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

LMC ClinRsrh Inc.Brampton, Brampton, Ontario, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female.
  • Age above or equal to 18 years at the time of signing informed consent.
  • Diagnosed with T2D (type 2 diabetes) greater than or equal to 180 days prior to the day of screening.
  • HbA1c (glycated haemoglobin) below or equal to 9.0 percent (below or equal to 75 mmol/mol).
  • Depending on biopsy/non-biopsy population:
  • For subjects in the non-biopsy population: Serum creatinine-based eGFR greater than or equal to 30 and below or equal to 75 mL/min/1.73 m^2(CKD-EPI).
  • For subjects in the biopsy sub-population: Serum creatinine-based eGFR greater than or equal to 40 and below or equal to 75 mL/min/1.73 m^2(CKD-EPI).
  • UACR ( Urinary albumin-to-creatinine ratio ) greater than or equal to 20 and below 5000 mg/g.
  • Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB)) unless such treatment is contraindicated or not tolerated.Treatment dose must be stable for at least 28 days prior to screening.

Exclusion criteria

  • Use of any glucagon-like peptide 1 receptor agonist (GLP-1 RA) within 30 days prior to screening.
  • A prior solid organ transplant or awaiting solid organ transplant.
  • Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening.
  • Presence or history of malignant neoplasms (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) within 5 years prior to the day of screening.
  • Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations.
  • Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and Visit 2. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
  • Treatment with systemic anti-inflammatory or immunosuppressant drugs within 90 days prior to screening. Stable treatment with acetylsalicylic acid for prevention of cardiovascular events and occasional use of propionic acid derivatives drugs (e.g. ibuprofen) is allowed.
  • Any contraindication for MRI according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared MR compatible.
  • Combination use of an ACE (angiotensin-converting enzyme) inhibitor and an ARB (angiotensin II receptor blockers).

Treatment and study plan

semaglutide

Drug

Semaglutide given subcutaneously (sc, under the skin) once weekly. Dose gradually increased over 8 weeks from 0.25 to 1.0 mg. The study will last for about 1 year.

Placebo (semaglutide)

Drug

Placebo (Semaglutide) given subcutaneously (sc, under the skin) once weekly. Dose gradually increased over 8 weeks from 0.25 to 1.0 mg. The study will last for about 1 year.

Primary outcomes

  1. Change in Kidney Oxygenation (Cortex), Blood Oxygenation-level Dependent Magnetic Resonance Imaging (BOLD MRI) (R2*)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in kidney oxygenation in cortex assessed by BOLD (blood oxygenation level dependent) MRI from baseline (week 0) to end of treatment (week 52) is presented. R2* is a measure used in BOLD MRI to indicate the level of tissue oxygenation. A higher R2* value means lower tissue oxygenation while a lower R2* value means higher tissue oxygenation.

  2. Change in Kidney Oxygenation (Medulla), BOLD MRI (R2*)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in kidney oxygenation in medulla assessed by BOLD (blood oxygenation level dependent) MRI from baseline (week 0) to end of treatment (week 52) is presented. R2* is a measure used in BOLD MRI to indicate the level of tissue oxygenation. A higher R2* value means lower tissue oxygenation while a lower R2* value means higher tissue oxygenation.

  3. Change in Global Kidney Perfusion (MRI)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in global kidney perfusion assessed by phase contrast MRI from baseline (week 0) to end of treatment (week 52) is presented.

  4. Change in Kidney Inflammation (Cortex), Longitudinal Relaxation Time (T1) Mapping (MRI)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in kidney inflammation in cortex assessed by T1 mapping MRI from baseline (week 0) to end of treatment (week 52) is presented.

  5. Change in Kidney Inflammation (Medulla), T1 Mapping (MRI)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in kidney inflammation in medulla assessed by T1 mapping MRI from baseline (week 0) to end of treatment (week 52) is presented.

Secondary outcomes

  1. Change in Gene Expression Assessed by Single Nucleus Ribonucleic Acid (RNA) Sequencing (Kidney Biopsy)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Changes in gene expression were assessed by single nucleus RNA sequencing (kidney biopsies) from baseline (week 0) to end of treatment (week 52). Cell type annotation was performed prior to the analysis. The analysis reports the log2 fold change in form of differential gene expression per cell type from baseline, comparing treatment arms. Genes are considered significant if fold change > 0.5 or < 0.5 and false discovery rate (FDR) <0.1; these criteria help identify biologically significant genes that are reliably differentially expressed in patients with conditions such as Type 2 diabetes and chronic kidney disease. The differential expression was estimated using a linear mixed model that included participant as a random effect. The cell types presented are those that contain these differentially expressed genes demonstrating the treatment response. This threshold is based on findings published in cross-sectional observational studies related to disease impact and gene activity.

  2. Change in Glomerular Basement Membrane Width (Kidney Biopsy)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in glomerular basement membrane width assessed in kidney biopsy from baseline (week 0) to end of treatment (week 52) is presented.

  3. Change in Apparent Diffusion Coefficient (ADC) (Cortex) (MRI)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in apparent diffusion coefficient in cortex assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented.

  4. Change in Apparent Diffusion Coefficient (ADC) (Medulla) (MRI)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in apparent diffusion coefficient in medulla assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented.

  5. Change in Mean Renal Artery Resistive Index (RARI) (MRI)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in renal arterial resistive index assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented. RARI measures the preservation of blood flow in renal arteries throughout the cardiac cycle and is therefore a measure for resistance of blood flow within the renal arteries. It serves as an indicator of kidney vascular health and potential arterial stiffness or obstruction. It is prognostic for primary cardiovascular and renal events in type 2 diabetes, where a lower RARI predicts a lower rate of events. RARI is calculated by relating the difference between blood flow at maximum velocity during the cardiac contraction phase (peak systolic velocity, PSV) and the speed at the end of the relaxation phase, at the point of minimal velocity (end diastolic velocity, EDV) with PSV, i.e., RARI = (PSV-EDV)/PSV.

  6. Change in Mean Arterial Flow (MRI)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in mean arterial flow assessed by MRI from baseline (week 0) to end of treatment (week 52) is presented.

  7. Change in Natriuresis (Urinary Sodium Excretion) (Urinalysis)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in natriuresis (urinary sodium excretion) (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented.

  8. Change in Albumin Excretion Rate (Urinalysis)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in albumin excretion rate (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented.

  9. Change in Kidney Function (Creatinine Clearance) (Urinalysis)

    Time frame: Baseline (week 0), End of treatment (week 52)

    Change in kidney function (creatinine clearance) (urinalysis) from baseline (week 0) to end of treatment (week 52) is presented.

Sponsors and collaborators

Lead sponsor

Novo Nordisk A/S

Industry

Registry information

Official study title

Renal Mode of Action of Semaglutide in Patients With Type 2 Diabetes and Chronic Kidney Disease

Acronym: REMODEL

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Apr 29, 2021
Registry last updated
Feb 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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