Clinical trial 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)
Official title: Renal Mode of Action of Semaglutide in Patients With Type 2 Diabetes and Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 2
Chronic Kidney Disease
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2021-04-29
Enrollment: 106
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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).

Primary outcomes:
measure: Change in kidney oxygenation (cortex), BOLD (blood oxygenation-level dependent) MRI ( magnetic resonance imaging )
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in kidney oxygenation (medulla), BOLD MRI(R2)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in global kidney perfusion (MRI)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in kidney inflammation (cortex), T1 mapping (MRI)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in kidney inflammation (medulla), T1 mapping (MRI)
timeFrame: From baseline (week 0) to end of treatment (week 52)
Secondary outcomes:
measure: Change in gene expression assessed by single nucleus RNA sequencing (kidney biopsy)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in glomerular basement membrane width (kidney biopsy)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in ADC (apparent diffusion coefficient) (cortex) (MRI)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in ADC (medulla) (MRI)
timeFrame: From baseline (week 0) to end of treatment (week 52
measure: Change in mean RARI (renal artery resistive index ) (MRI)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in mean arterial flow (MRI)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in natriuresis (urinary sodium excretion) (urinalysis)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in albumin excretion rate (urinalysis)
timeFrame: From baseline (week 0) to end of treatment (week 52)
measure: Change in kidney function (creatinine clearance) (urinalysis
timeFrame: From baseline (week 0) to end of treatment (week 52
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Academic Medical Research Institute
state: California
city: San Dimas
country: United States
facility: N America Res Inst - San Dimas
state: California
city: Aurora
country: United States
facility: UC Anschutz Medical Campus
state: Colorado
city: Orlando
country: United States
facility: Advent Health-Res Inst
state: Florida
city: Kansas City
country: United States
facility: Clinical Research Consultants, LLC
state: Missouri
city: Houston
country: United States
facility: Prolato Clinical Research Cntr
state: Texas
city: San Antonio
country: United States
facility: NE Clin Res of San Antonio
state: Texas
city: Seattle
country: United States
facility: Univ of Washington Med Ctr
state: Washington
city: Spokane
country: United States
facility: Providence Medical Research Center
state: Washington
city: Toronto
country: Canada
facility: UHN-Toronto General Hospital
state: Ontario
city: Copenhagen
country: Denmark
facility: Nefrologisk Klinik P 2132
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: AMIENS cedex 1
country: France
facility: Centre Hospitalier Universitaire Amiens Picardie-Site Sud
city: Bois-Guillaume
country: France
facility: Centre Hospitalier Universitaire de Rouen - Hopital de Bois Guillaume
city: Grenoble - Cédex 09
country: France
facility: Centre Hospitalier Universitaire Grenoble Alpes-Site Nord Michallon-2
city: Reims
country: France
facility: Centre Hospitalier Universitaire Reims-Hopital Maison Blanche
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse-Hopital Rangueil-1
city: Milano
country: Italy
facility: Istituto Scientifico San Raffaele
state: MI
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova Clin.Med.3
city: Roma
country: Italy
facility: Azienda Ospedaliero - Universitaria Sant'Andrea
city: Radom
country: Poland
facility: Centrum Medyczne "Diabetika"
city: Szczecin
country: Poland
facility: SPSK nr 2 PUM, Kl. Nefrologii, Transplantologii i Ch. Wewn.
city: Warszawa
country: Poland
facility: Miedzyleski Szpital Specjalistyczny, Oddzial Nefrologiczny
city: Zabrze
country: Poland
facility: Prywatny Gabinet Janusz Gumprecht
city: Durban
country: South Africa
facility: Maxwell Centre
state: KwaZulu-Natal
city: Durban
country: South Africa
facility: Precise Clinical Solutions (Pty) Ltd
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Prof Rayner_Division of Nephrology
state: Western Cape
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (Dept.2834)
role: STUDY_DIRECTOR
References: