SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes

Obesity Clinical Trial

— SMART  

Official title:

SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04889183
• Other study ID #: 202100166
• Secondary ID: 2021-001247-27
• Status: Completed
• Phase: Phase 3
• Start date: March 14, 2022
• Est. completion date: May 28, 2024

Study information

• Verified date: June 2024
• Source: University Medical Center Groningen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study to assess the effects of weekly subcutaneous administration of the GLP1-RA semaglutide 2.4mg on kidney function parameters in obese/overweight individuals at high risk of CKD progression.

Description:

Glucagon Like Peptide 1 Receptor Agonist (GLP1-RA) therapies have been introduced as antidiabetic drugs. In addition, GLP1-RA therapies reduce body weight, in patients with and without diabetes, without inducing hypoglycemia. Moreover, GLP1-RA reduce albuminuria in patients with type 2 diabetes, and liraglutide and semaglutide have been shown to improve various risk markers of CKD progression in non-diabetic obese individuals. It is therefore likely that these agents delay progression of kidney function decline in high risk obese/overweight, non-diabetic individuals.

The main objective of the study is to assess the albuminuria lowering effects of semaglutide 2.4 mg s.c. once weekly (Semaglutide 3 mg/ml) compared to placebo in obese/overweight non-diabetic individuals with elevated albuminuria. This will be tested in a 24-week randomized placebo controlled double-blind two arm parallel clinical trial with a 4 week wash-out period after 24 weeks double blind treatment to assess off drug effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: May 28, 2024
• Est. primary completion date: May 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• Body Mass index = 27 kg/m2

• Albuminuria = 30 mg/g and = 3500 mg/g

• eGFR = 25 ml/min/1.73m2

• Stable renal function prior to entry into the study defined as no more than 30% eGFR change in 3 months prior to enrolment

• Signed Informed Consent

Exclusion Criteria:

• Diagnosis with type 1 or type 2 Diabetes

• Hba1c = 6.5% at screening

• Cardiovascular disease event in 3 months prior to enrollment

• Treatment with GLP-1 RA < 4 weeks prior to screening

• Uncontrolled thyroid disease TSH>6.0 mIU/L or <0.4 mIU/L at screening

• Acute pancreatitis < 180 days prior to screening

• History or presence of chronic pancreatitis

• Females of child-bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant or are not using adequate contraceptive measures

Related Conditions & MeSH terms

• Albuminuria
• Obesity

Intervention

Drug:
• Semaglutide
Patients will be treated for 24 weeks with semaglutide 3.0 mlg/ml s.c. once weekly. The starting dose of semaglutide will be 0.24 mg per week subcutaneous injection with increasing doses at 4, 8, 12, and 16 weeks to 0.5, 1,0, 1.7 and 2.4 mg.
• Placebo
Patients will receive a matching placebo sc. once weekly during the treatment period of 24 weeks.

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Division of Nephrology University Health Network, University of Toronto	Toronto	Ontario
Germany	University Hospital Erlangen	Erlangen
Germany	University Hospital Wuerzburg	Würzburg
Netherlands	Dept Internal Medicine, division of Nephrology Hospital Group Twente	Almelo
Netherlands	Rijnstate	Arnhem	Gelderland
Netherlands	Martini Ziekenhuis	Groningen
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Isala	Zwolle	Overijssel
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Vall d'Hebron University Hospital	Barcelona
Spain	Hospital Da Costa Burela	Lugo
Spain	Hospital Clínico Universitario	Valencia

Sponsors (2)

Lead Sponsor	Collaborator
University Medical Center Groningen	Novo Nordisk A/S

Countries where clinical trial is conducted

Canada,  Germany,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline to week 24 in urinary albumin:creatinine ratio (UACR)	Measured in first morning void	Week 1 to week 24
Secondary	estimated glomerular filtration rate (eGFR)	Change from baseline to week 24 in estimated glomerular filtration rate (eGFR)	Week 1 to week 24
Secondary	Iohexol measured glomerular filtration rate (GFR)	Change from baseline to week 24 in Iohexol measured glomerular filtration rate (GFR)	Week 1 to week 24
Secondary	urinary albumin:creatinine ratio (UACR) during wash-out	Change in urinary albumin:creatinine ratio (UACR) during wash-out	week 24 to 28
Secondary	estimated glomerular filtration rate (eGFR) during wash-out	Change in estimated glomerular filtration rate (eGFR) during wash-out	week 24 to 28
Secondary	body weight	Change from baseline to week 24 in body weight	Week 1 to week 24
Secondary	hip circumference	Change from baseline to week 24 in hip circumference	Week 1 to week 24
Secondary	systolic and diastolic blood pressure	Change from baseline to week 24 in systolic and diastolic blood pressure	Week 1 to week 24
Secondary	extracellular fluid	Change from baseline to week 24 in extracellular fluid as measured by bio-impedance	Week 1 to week 24
Secondary	high sensitivity C-reactive protein (CRP)	Change from baseline to week 24 in high sensitivity C-reactive protein (CRP)	Week 1 to week 24