Clinical trial NCT04889183: SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes
Official title: SeMaglutide and Albuminuria Reduction Trial in Obese Individuals Without Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Obesity
Albuminuria
Keywords: SMART
Semaglutide
UMCG
Lambers Heerspink
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2021-05-17
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized placebo controlled double-blind two arm parallel clinical trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change from baseline to week 24 in urinary albumin:creatinine ratio (UACR)
timeFrame: Week 1 to week 24
Secondary outcomes:
measure: estimated glomerular filtration rate (eGFR)
timeFrame: Week 1 to week 24
measure: Iohexol measured glomerular filtration rate (GFR)
timeFrame: Week 1 to week 24
measure: urinary albumin:creatinine ratio (UACR) during wash-out
timeFrame: week 24 to 28
measure: estimated glomerular filtration rate (eGFR) during wash-out
timeFrame: week 24 to 28
measure: body weight
timeFrame: Week 1 to week 24
measure: hip circumference
timeFrame: Week 1 to week 24
measure: systolic and diastolic blood pressure
timeFrame: Week 1 to week 24
measure: extracellular fluid
timeFrame: Week 1 to week 24
measure: high sensitivity C-reactive protein (CRP)
timeFrame: Week 1 to week 24
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Toronto
country: Canada
facility: Division of Nephrology University Health Network, University of Toronto
state: Ontario
city: Erlangen
country: Germany
facility: University Hospital Erlangen
city: Würzburg
country: Germany
facility: University Hospital Wuerzburg
city: Arnhem
country: Netherlands
facility: Rijnstate
state: Gelderland
city: Zwolle
country: Netherlands
facility: Isala
state: Overijssel
city: Almelo
country: Netherlands
facility: Dept Internal Medicine, division of Nephrology Hospital Group Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Lugo
country: Spain
facility: Hospital Da Costa Burela
city: Valencia
country: Spain
facility: Hospital Clínico Universitario
Study officials:
References: