SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes (SMART)

• ClinicalTrials.gov Identifier: NCT04889183
• Recruitment Status: Enrolling by invitation
• First Posted: May 17, 2021
• Last Update Posted: March 28, 2023
• Sponsor: University Medical Center Groningen
• Collaborator: Novo Nordisk A/S
• Information provided by (Responsible Party): Hiddo Lambers Heerspink, University Medical Center Groningen

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Obesity; Albuminuria	Drug: Semaglutide; Drug: Placebo	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 98 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized placebo controlled double-blind two arm parallel clinical trial
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes
• Actual Study Start Date: March 14, 2022
• Estimated Primary Completion Date: May 2023
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Semaglutide; Patients will be treated with semaglutide 3 mg/ml s.c. once weekly for 24 weeks. The starting dose of semaglutide will be 0.24 mg subcutaneous injection with increasing doses at 4, 8, 12, and 16 weeks to 0.5, 1,0, 1.7 and 2.4 mg once weekly.	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 Comparator: Placebo; Patients will receive a matching placebo s.c. once weekly.	Drug: Placebo; Patients will receive a matching placebo sc. once weekly during the treatment period of 24 weeks.

Outcome Measures

Primary Outcome Measures :

1. Change from baseline to week 24 in urinary albumin:creatinine ratio (UACR) [ Time Frame: Week 1 to week 24 ]
   Measured in first morning void

Secondary Outcome Measures :

1. estimated glomerular filtration rate (eGFR) [ Time Frame: Week 1 to week 24 ]
   Change from baseline to week 24 in estimated glomerular filtration rate (eGFR)
2. Iohexol measured glomerular filtration rate (GFR) [ Time Frame: Week 1 to week 24 ]
   Change from baseline to week 24 in Iohexol measured glomerular filtration rate (GFR)
3. urinary albumin:creatinine ratio (UACR) during wash-out [ Time Frame: week 24 to 28 ]
   Change in urinary albumin:creatinine ratio (UACR) during wash-out
4. estimated glomerular filtration rate (eGFR) during wash-out [ Time Frame: week 24 to 28 ]
   Change in estimated glomerular filtration rate (eGFR) during wash-out
5. body weight [ Time Frame: Week 1 to week 24 ]
   Change from baseline to week 24 in body weight
6. hip circumference [ Time Frame: Week 1 to week 24 ]
   Change from baseline to week 24 in hip circumference
7. systolic and diastolic blood pressure [ Time Frame: Week 1 to week 24 ]
   Change from baseline to week 24 in systolic and diastolic blood pressure
8. extracellular fluid [ Time Frame: Week 1 to week 24 ]
   Change from baseline to week 24 in extracellular fluid as measured by bio-impedance
9. high sensitivity C-reactive protein (CRP) [ Time Frame: Week 1 to week 24 ]
   Change from baseline to week 24 in high sensitivity C-reactive protein (CRP)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Alberta

University of Calgary

Calgary, Alberta, Canada, 3230

Canada, Ontario

Division of Nephrology University Health Network, University of Toronto

Toronto, Ontario, Canada, M5G 2C4

Germany

University Hospital Erlangen

Erlangen, Germany, 91054

University Hospital Wuerzburg

Würzburg, Germany, 97080

Netherlands

Rijnstate

Arnhem, Gelderland, Netherlands, 6815 AD

Isala

Zwolle, Overijssel, Netherlands, 8025 AB

Dept Internal Medicine, division of Nephrology Hospital Group Twente

Almelo, Netherlands, 7609 PP

University Medical Center Groningen

Groningen, Netherlands, 9713 GZ

Martini Ziekenhuis

Groningen, Netherlands, 9728 NT

Spain

Vall d'Hebron University Hospital

Barcelona, Spain, 08035

Hospital Universitari de Bellvitge

Barcelona, Spain, 08907

Hospital Da Costa Burela

Lugo, Spain, 27880

Hospital Clínico Universitario

Valencia, Spain, 46010

Sponsors and Collaborators

University Medical Center Groningen

Novo Nordisk A/S

More Information

• Responsible Party: Hiddo Lambers Heerspink, Professor at the Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen
• ClinicalTrials.gov Identifier: NCT04889183
• Other Study ID Numbers: 202100166; 2021-001247-27 ( EudraCT Number )
• First Posted: May 17, 2021
• Last Update Posted: March 28, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Albuminuria; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations