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Renal Effects of Treatment With Empagliflozin Alone or in Combination With Semaglutide in Patients With Type 2 Diabetes and Albuminuria (EmpaSema)

Primary Purpose

Type 2 Diabetes With Renal Manifestations

Status
Unknown status
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Semaglutide, 1.34 mg/mL
Placebo, 1,34 mg/mL
Empagliflozin 25 MG
Sponsored by
Steno Diabetes Center Copenhagen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes With Renal Manifestations

Eligibility Criteria

18 Years - 100 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Given written informed consent
  2. Male or female patients ≥ 18 years with type 2 diabetes (WHO criteria).
  3. UACR > 100 mg/g within a year of informed consent documented in the medical files.
  4. eGFR ≥ 30 ml/min/1.73 m2 (estimated by CKD-EPI formula) within 3 months of informed consent documented in the medical files. The eGFR measured at visit 0 has to meet the criteria as well.
  5. Fertile female must use chemical, hormonal and mechanical contraceptives, be in menopause (i.e. must not have had regular menstrual bleeding for at least one year), have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least six months prior to screening
  6. Treated with maximal tolerated dose of an angiotensin-converting-enzyme inhibitor or an angiotensin II receptor blocker, 4 weeks prior to randomisation. If the participants are not treated with maximal tolerated dosis the investigator will increase the dose 4 weeks prior randomisation if tolerated.
  7. Ability to communicate with the investigator and understand informed consent.

Exclusion Criteria:

  1. Type 1 diabetes
  2. Known or suspected hypersensitivity to trial product(s) or related products
  3. Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial
  4. Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months.
  5. Previous bowel resection
  6. Body mass index < 18.5 kg/m2
  7. Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods
  8. Known or suspected abuse of alcohol or narcotics.
  9. Participant in another intervention study

Sites / Locations

  • Steno Diabetes Center Copenhagen

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Semaglutide 1,34 mg/ml

Placebo 1,34 mg/ml

Arm Description

Semaglutide 1,34 mg/ml (solution for subcutaneous injection in pre-filled pen-injector). At randomisation, the participants start with doses of 0.25 mg/week for 4 weeks, then escalate to doses of 0.5 mg/week for 4 weeks, and thereafter escalate to 1.0 mg/week if tolerated until 52 weeks of total treatment.

Placebo 1,34 mg/ml (solution for subcutaneous injection in pre-filled pen-injector). At randomisation, the participants start with doses of 0.25 mg/week for 4 weeks, then escalate to doses of 0.5 mg/week for 4 weeks, and thereafter escalate to 1.0 mg/week if tolerated until 52 weeks of total treatment.

Outcomes

Primary Outcome Measures

Albuminuria
Change in albuminuria

Secondary Outcome Measures

Hba1c
Change in Hba1c
GFR
Change in measured kidney function (GFR)
24 hour blood pressure
Change in 24 hour blood pressure
Vasoactive hormones
Change in vasoactive hormones (o Plasma renin concentration, plasma renin activity, angiotensin I, angiotensin II, aldosterone, copeptin)
Inflammatory and endothelial biomarkers
Change in inflammatory and endothelial biomarkers (Von Willebrand factor, sVCAM-1, sICAM-1, E-selectin, b-leucocytes, s-CRP, IL-6, osteopontin, TNF-α)

Full Information

First Posted
August 14, 2019
Last Updated
August 16, 2019
Sponsor
Steno Diabetes Center Copenhagen
Collaborators
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT04061200
Brief Title
Renal Effects of Treatment With Empagliflozin Alone or in Combination With Semaglutide in Patients With Type 2 Diabetes and Albuminuria
Acronym
EmpaSema
Official Title
Renal Effects of Treatment With Empagliflozin Alone or in Combination With Semaglutide in Patients With Type 2 Diabetes and Albuminuria - A Double Blinded, Randomised, Placebo Controlled, Parallel, Single Center Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2019 (Anticipated)
Primary Completion Date
July 1, 2021 (Anticipated)
Study Completion Date
August 1, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Steno Diabetes Center Copenhagen
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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objective of this study is to evaluate the effect of treatment with semaglutide 1.34 mg/ml in combination with empagliflozin 25 mg, compared to treatment with empagliflozin 25 mg in combination with placebo on albuminuria in participants with type 2 diabetes and albuminuria. In a randomised, placebo-controlled, double-blinded, parallel trial we will include 80 patients with type 2 diabetes and albuminuria. Patients will start in a run-in phase of 26 weeks with empagliflozin 25 mg alone. After that, the patients will be randomised 1:1 to an active treatment period with semaglutide of 26 weeks or placebo for 26 weeks. The primary endpoint is change from randomisation to week 52 in albuminuria, measured in three morning urine samples.
Detailed Description
Patients with type 2 diabetes are at high risk of developing diabetic nephropathy. The most promising antidiabetic agents on the market with potential to preserve renal function are endogenous glucagon like peptide (GLP-1) agonists and selective sodium-glucose cotransporter 2 (SGLT2) inhibitors. The LEADER trial demonstrated that treatment with liraglutide (GLP-1 agonist) resulted in 22% lower risk of renal composite outcome. The EMPA-REG trial demonstrated that treatment with empagliflozin (SGLT2 inhibitor) reduced the same renal composite outcome by 39%. Previous studies have mainly focused on glycaemic parameters when combining a GLP-1 agonist and SGLT2 inhibitor. From a renal perspective, it is of major interest to investigate if a stepwise initiation of semaglutide or placebo added to ongoing empagliflozin therapy would complement or have an additive effect on renal parameters. In a randomised, placebo-controlled, double-blinded, parallel trial we will include 80 patients with type 2 diabetes and albuminuria. Patients will start in a run-in phase of 26 weeks with empagliflozin 25 mg alone. After that, the patients will be randomised 1:1 to an active treatment period with semaglutide of 26 weeks or placebo for 26 weeks.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes With Renal Manifestations

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blinded
Allocation
Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Semaglutide 1,34 mg/ml
Arm Type
Active Comparator
Arm Description
Semaglutide 1,34 mg/ml (solution for subcutaneous injection in pre-filled pen-injector). At randomisation, the participants start with doses of 0.25 mg/week for 4 weeks, then escalate to doses of 0.5 mg/week for 4 weeks, and thereafter escalate to 1.0 mg/week if tolerated until 52 weeks of total treatment.
Arm Title
Placebo 1,34 mg/ml
Arm Type
Placebo Comparator
Arm Description
Placebo 1,34 mg/ml (solution for subcutaneous injection in pre-filled pen-injector). At randomisation, the participants start with doses of 0.25 mg/week for 4 weeks, then escalate to doses of 0.5 mg/week for 4 weeks, and thereafter escalate to 1.0 mg/week if tolerated until 52 weeks of total treatment.
Intervention Type
Drug
Intervention Name(s)
Semaglutide, 1.34 mg/mL
Intervention Description
After informed consent, subjects will be initiated on open-label empagliflozin 25 mg or maximal tolerated dosis once daily during a run-in period of 26 weeks. Participants will be randomized and up titrated to semaglutide 1.34 mg/ml or matching placebo once weekly during the following 26 weeks in a 1:1 ratio.
Intervention Type
Other
Intervention Name(s)
Placebo, 1,34 mg/mL
Intervention Description
Participants will be randomised to either semaglutide or placebo as an add on treatment after 26 weeks of intervention with empagliflozin 25 mg.
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 25 MG
Intervention Description
After informed consent, subjects will be initiated on open-label empagliflozin 25 mg or maximal tolerated dosis once daily during a run-in period of 26 weeks.
Primary Outcome Measure Information:
Title
Albuminuria
Description
Change in albuminuria
Time Frame
From randomisation to week 52
Secondary Outcome Measure Information:
Title
Hba1c
Description
Change in Hba1c
Time Frame
From randomisation to week 52
Title
GFR
Description
Change in measured kidney function (GFR)
Time Frame
From randomisation to week 52
Title
24 hour blood pressure
Description
Change in 24 hour blood pressure
Time Frame
From randomisation to week 52
Title
Vasoactive hormones
Description
Change in vasoactive hormones (o Plasma renin concentration, plasma renin activity, angiotensin I, angiotensin II, aldosterone, copeptin)
Time Frame
From randomisation to week 52
Title
Inflammatory and endothelial biomarkers
Description
Change in inflammatory and endothelial biomarkers (Von Willebrand factor, sVCAM-1, sICAM-1, E-selectin, b-leucocytes, s-CRP, IL-6, osteopontin, TNF-α)
Time Frame
From randomisation to week 52

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Given written informed consent Male or female patients ≥ 18 years with type 2 diabetes (WHO criteria). UACR > 100 mg/g within a year of informed consent documented in the medical files. eGFR ≥ 30 ml/min/1.73 m2 (estimated by CKD-EPI formula) within 3 months of informed consent documented in the medical files. The eGFR measured at visit 0 has to meet the criteria as well. Fertile female must use chemical, hormonal and mechanical contraceptives, be in menopause (i.e. must not have had regular menstrual bleeding for at least one year), have undergone bilateral oophorectomy or have been surgically sterilized or hysterectomised at least six months prior to screening Treated with maximal tolerated dose of an angiotensin-converting-enzyme inhibitor or an angiotensin II receptor blocker, 4 weeks prior to randomisation. If the participants are not treated with maximal tolerated dosis the investigator will increase the dose 4 weeks prior randomisation if tolerated. Ability to communicate with the investigator and understand informed consent. Exclusion Criteria: Type 1 diabetes Known or suspected hypersensitivity to trial product(s) or related products Cancer (except basal cell skin cancer or squamous cell skin cancer) or any other clinically significant disorder, except for conditions associated with type 2 diabetes history, which in the investigators opinion could interfere with the results of the trial Cardiac disease defined as: Decompensated heart failure (NYHA class III-IV) and or diagnosis of unstable angina pectoris and/or myocardial infarction within the last 6 months. Previous bowel resection Body mass index < 18.5 kg/m2 Females of childbearing potential who are pregnant, breast-feeding, intend to become pregnant or are not using adequate contraceptive methods Known or suspected abuse of alcohol or narcotics. Participant in another intervention study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Rossing, MD
Phone
30912975
Email
peter.rossing@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Suvanjaa Sivalingam
Phone
24405599
Email
suvanjaa.sivalingam.02@regionh.dk
Facility Information:
Facility Name
Steno Diabetes Center Copenhagen
City
Gentofte
ZIP/Postal Code
2820
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
No

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Renal Effects of Treatment With Empagliflozin Alone or in Combination With Semaglutide in Patients With Type 2 Diabetes and Albuminuria

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