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)

Diabetes Mellitus, Type 2 Clinical Trial

— REMODEL  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04865770
• Other study ID #: NN9535-4662
• Secondary ID: U1111-1248-79122
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 28, 2021
• Est. completion date: November 18, 2024

Study information

• Verified date: May 2024
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 105
• Est. completion date: November 18, 2024
• Est. primary completion date: October 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. 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).

2. 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).

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Semaglutide
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)
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.

Locations

Country	Name	City	State
Canada	UHN-Toronto General Hospital	Toronto	Ontario
Denmark	Nefrologisk Klinik P 2132	Copenhagen
Denmark	Steno Diabetes Center Copenhagen	Herlev
France	Centre Hospitalier Universitaire Amiens Picardie-Site Sud	AMIENS cedex 1
France	Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume	Bois-Guillaume
France	Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-2	Grenoble - Cédex 09
France	Centre Hospitalier Universitaire Reims-Hopital Maison Blanche	Reims
France	Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-1	Toulouse
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Istituto Scientifico San Raffaele	Milano	MI
Italy	Azienda Ospedaliera di Padova Clin.Med.3	Padova
Italy	Azienda Ospedaliero - Universitaria Sant'Andrea	Roma
Poland	In-Vivo Sp. z o.o.	Bydgoszcz
Poland	Centrum Medyczne "Diabetika"	Radom
Poland	SPSK nr 2 PUM, Kl. Nefrologii, Transplantologii i Ch. Wewn.	Szczecin
Poland	Miedzyleski Szpital Specjalistyczny, Oddzial Nefrologiczny	Warszawa
Poland	Prywatny Gabinet Janusz Gumprecht	Zabrze
South Africa	Prof Rayner	Cape Town	Western Cape
South Africa	Maxwell Centre	Durban	KwaZulu-Natal
South Africa	Precise Clinical Solutions (Pty) Ltd	Durban	KwaZulu-Natal
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital de Bellvitge	Hospitalet de Llobregat
Spain	Hospital Clínico Universitario de Valencia	Valencia
United States	UC Anschutz Medical Campus	Aurora	Colorado
United States	Prolato Clinical Research Center	Houston	Texas
United States	Clinical Research Consultants, LLC	Kansas City	Missouri
United States	Academic Medical Research Institute	Los Angeles	California
United States	Advent Health-Res Inst	Orlando	Florida
United States	NE Clin Res of San Antonio	San Antonio	Texas
United States	N America Res Inst - San Dimas	San Dimas	California
United States	Univ of Washington Med Ctr	Seattle	Washington
United States	Providence Medical Research Center	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  France,  Italy,  Poland,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in kidney oxygenation (cortex), BOLD (blood oxygenation-level dependent) MRI ( magnetic resonance imaging )	ratio	From baseline (week 0) to end of treatment (week 52)
Primary	Change in kidney oxygenation (medulla), BOLD MRI(R2)	ratio	From baseline (week 0) to end of treatment (week 52)
Primary	Change in global kidney perfusion (MRI)	ratio	From baseline (week 0) to end of treatment (week 52)
Primary	Change in kidney inflammation (cortex), T1 mapping (MRI)	ratio	From baseline (week 0) to end of treatment (week 52)
Primary	Change in kidney inflammation (medulla), T1 mapping (MRI)	ratio	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in gene expression assessed by single nucleus RNA sequencing (kidney biopsy)	log2 fold-change	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in glomerular basement membrane width (kidney biopsy)	nm	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in ADC (apparent diffusion coefficient) (cortex) (MRI)	ratio	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in ADC (medulla) (MRI)	ratio	From baseline (week 0) to end of treatment (week 52
Secondary	Change in mean RARI (renal artery resistive index ) (MRI)	ratio	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in mean arterial flow (MRI)	ratio	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in natriuresis (urinary sodium excretion) (urinalysis)	mmol/l	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in albumin excretion rate (urinalysis)	mg/24 hours	From baseline (week 0) to end of treatment (week 52)
Secondary	Change in kidney function (creatinine clearance) (urinalysis	ml/min/1.73 m^2	From baseline (week 0) to end of treatment (week 52