SMART: SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes

Sponsor

University Medical Center Groningen (Other)

Overall Status

Enrolling by invitation

CT.gov ID

NCT04889183

Collaborator

Novo Nordisk A/S (Industry)

Enrollment

Locations

Arms

13.6

Anticipated Duration (Months)

7.5

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

98 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized placebo controlled double-blind two arm parallel clinical trialRandomized 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 :

Mar 14, 2022

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 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.

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

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	University of Calgary	Calgary	Alberta	Canada	3230
2	Division of Nephrology University Health Network, University of Toronto	Toronto	Ontario	Canada	M5G 2C4
3	University Hospital Erlangen	Erlangen		Germany	91054
4	University Hospital Wuerzburg	Würzburg		Germany	97080
5	Rijnstate	Arnhem	Gelderland	Netherlands	6815 AD
6	Isala	Zwolle	Overijssel	Netherlands	8025 AB
7	Dept Internal Medicine, division of Nephrology Hospital Group Twente	Almelo		Netherlands	7609 PP
8	University Medical Center Groningen	Groningen		Netherlands	9713 GZ
9	Martini Ziekenhuis	Groningen		Netherlands	9728 NT
10	Vall d'Hebron University Hospital	Barcelona		Spain	08035
11	Hospital Universitari de Bellvitge	Barcelona		Spain	08907
12	Hospital Da Costa Burela	Lugo		Spain	27880
13	Hospital Clínico Universitario	Valencia		Spain	46010

Sponsors and Collaborators

University Medical Center Groningen
Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

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

First Posted:

May 17, 2021

Last Update Posted:

Apr 5, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Albuminuria

Study Results

No Results Posted as of Apr 5, 2022