SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes

Conditions
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Obesity, Albuminuria

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo controlled double-blind two arm parallel clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>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<br>* 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.<br>|
| Placebo Comparator: Placebo<br>Patients will receive a matching placebo s.c. once weekly. | Drug: Placebo<br>* Patients will receive a matching placebo sc. once weekly during the treatment period of 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to week 24 in urinary albumin:creatinine ratio (UACR) | Measured in first morning void | Week 1 to week 24 | 

Secondary Outcome Measures

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