SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes (SMART)
Primary Purpose
Obesity, Albuminuria
Status
Enrolling by invitation
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Semaglutide
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Obesity
Eligibility 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
Sites / Locations
- University of Calgary
- Division of Nephrology University Health Network, University of Toronto
- University Hospital Erlangen
- University Hospital Wuerzburg
- Rijnstate
- Isala
- Dept Internal Medicine, division of Nephrology Hospital Group Twente
- University Medical Center Groningen
- Martini Ziekenhuis
- Vall d'Hebron University Hospital
- Hospital Universitari de Bellvitge
- Hospital Da Costa Burela
- Hospital Clínico Universitario
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Semaglutide
Placebo
Arm Description
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.
Patients will receive a matching placebo s.c. once weekly.
Outcomes
Primary Outcome Measures
Change from baseline to week 24 in urinary albumin:creatinine ratio (UACR)
Measured in first morning void
Secondary Outcome Measures
estimated glomerular filtration rate (eGFR)
Change from baseline to week 24 in estimated glomerular filtration rate (eGFR)
Iohexol measured glomerular filtration rate (GFR)
Change from baseline to week 24 in Iohexol measured glomerular filtration rate (GFR)
urinary albumin:creatinine ratio (UACR) during wash-out
Change in urinary albumin:creatinine ratio (UACR) during wash-out
estimated glomerular filtration rate (eGFR) during wash-out
Change in estimated glomerular filtration rate (eGFR) during wash-out
body weight
Change from baseline to week 24 in body weight
hip circumference
Change from baseline to week 24 in hip circumference
systolic and diastolic blood pressure
Change from baseline to week 24 in systolic and diastolic blood pressure
extracellular fluid
Change from baseline to week 24 in extracellular fluid as measured by bio-impedance
high sensitivity C-reactive protein (CRP)
Change from baseline to week 24 in high sensitivity C-reactive protein (CRP)
Full Information
NCT ID
NCT04889183
First Posted
May 6, 2021
Last Updated
September 28, 2023
Sponsor
University Medical Center Groningen
Collaborators
Novo Nordisk A/S
1. Study Identification
Unique Protocol Identification Number
NCT04889183
Brief Title
SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes
Acronym
SMART
Official Title
SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
March 14, 2022 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
Collaborators
Novo Nordisk A/S
4. Oversight
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
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Albuminuria
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized placebo controlled double-blind two arm parallel clinical trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
98 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Semaglutide
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive a matching placebo s.c. once weekly.
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Patients will receive a matching placebo sc. once weekly during the treatment period of 24 weeks.
Primary Outcome Measure Information:
Title
Change from baseline to week 24 in urinary albumin:creatinine ratio (UACR)
Description
Measured in first morning void
Time Frame
Week 1 to week 24
Secondary Outcome Measure Information:
Title
estimated glomerular filtration rate (eGFR)
Description
Change from baseline to week 24 in estimated glomerular filtration rate (eGFR)
Time Frame
Week 1 to week 24
Title
Iohexol measured glomerular filtration rate (GFR)
Description
Change from baseline to week 24 in Iohexol measured glomerular filtration rate (GFR)
Time Frame
Week 1 to week 24
Title
urinary albumin:creatinine ratio (UACR) during wash-out
Description
Change in urinary albumin:creatinine ratio (UACR) during wash-out
Time Frame
week 24 to 28
Title
estimated glomerular filtration rate (eGFR) during wash-out
Description
Change in estimated glomerular filtration rate (eGFR) during wash-out
Time Frame
week 24 to 28
Title
body weight
Description
Change from baseline to week 24 in body weight
Time Frame
Week 1 to week 24
Title
hip circumference
Description
Change from baseline to week 24 in hip circumference
Time Frame
Week 1 to week 24
Title
systolic and diastolic blood pressure
Description
Change from baseline to week 24 in systolic and diastolic blood pressure
Time Frame
Week 1 to week 24
Title
extracellular fluid
Description
Change from baseline to week 24 in extracellular fluid as measured by bio-impedance
Time Frame
Week 1 to week 24
Title
high sensitivity C-reactive protein (CRP)
Description
Change from baseline to week 24 in high sensitivity C-reactive protein (CRP)
Time Frame
Week 1 to week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Facility Information:
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
3230
Country
Canada
Facility Name
Division of Nephrology University Health Network, University of Toronto
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2C4
Country
Canada
Facility Name
University Hospital Erlangen
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
University Hospital Wuerzburg
City
Würzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Rijnstate
City
Arnhem
State/Province
Gelderland
ZIP/Postal Code
6815 AD
Country
Netherlands
Facility Name
Isala
City
Zwolle
State/Province
Overijssel
ZIP/Postal Code
8025 AB
Country
Netherlands
Facility Name
Dept Internal Medicine, division of Nephrology Hospital Group Twente
City
Almelo
ZIP/Postal Code
7609 PP
Country
Netherlands
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Martini Ziekenhuis
City
Groningen
ZIP/Postal Code
9728 NT
Country
Netherlands
Facility Name
Vall d'Hebron University Hospital
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitari de Bellvitge
City
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Da Costa Burela
City
Lugo
ZIP/Postal Code
27880
Country
Spain
Facility Name
Hospital Clínico Universitario
City
Valencia
ZIP/Postal Code
46010
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes
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