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The Effect of Glucagon-like-peptide 1 (GLP-1) Receptor Agonism on Diabetic Kidney Disease

Primary Purpose

Diabetic Kidney Disease

Status
Completed
Phase
Phase 3
Locations
Ireland
Study Type
Interventional
Intervention
Liraglutide
Sponsored by
Karl Neff
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetic Kidney Disease focused on measuring kidney, diabetes, glp-1

Eligibility Criteria

30 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Type 2 diabetes with a HbA1c of 42-75mmol/mol (6-9%DCCT)
  • Male or female aged above 30 years
  • Have a negative pregnancy test at screening (women of child bearing potential only)
  • Body mass index (BMI) of 25kg/m2 or greater
  • On a renin-angiotensin system antagonist, at a stable dose, for at least 8 weeks before inclusion into the study
  • Established microalbuminuria
  • Estimated glomerular filtration rate (eGFR) 30ml/min/1.73m2 or above by Modification of Diet in Renal Disease (MDRD) formula

Exclusion Criteria:

  • Patients with any cognitive impediment that preclude the patient from giving free and informed consent
  • Patients on dipeptidyl peptidase 4 inhibitors or thiazolidinedione treatment
  • Patients with stage 4-5 renal disease, defined as an eGFR of 30ml/min/1.73m2 or less
  • Patients who have used a GLP-1 agent in the last 6 months
  • Female patients of child bearing potential who are pregnant, breastfeeding, or unwilling to practice an acceptable barrier and/or hormonal method of contraception or abstinence during participation in the study
  • Previous pancreatitis
  • Hypersensitivity to GLP-1 analogues
  • Proliferative diabetic retinopathy
  • Any other contraindications, as per the SmPC for liraglutide
  • Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the dosing requirements
  • Concurrent treatment with an investigational drug or participation in another clinical trial
  • Use of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, preceding the first dose of investigational medicinal product

Sites / Locations

  • St Vincent's Healthcare Group

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Liraglutide

Control

Arm Description

Liraglutide 0.6 mg daily

Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist

Outcomes

Primary Outcome Measures

MCP-1:Creatinine Ratio in Urine
Spot urine sample for MCP-1 and creatinine

Secondary Outcome Measures

Urine Albumin:Creatinine Ratio
Spot urine sample for albumin and creatinine
Urinary Albumin Excretion Rate
Albuminuria as Measured by 24 Hour Albumin Excretion Rate
sCD163 in Serum
Serum sample for sCD163
sCD163:Creatinine Ratio in Urine
Spot urine sample for MCP-1 and creatinine

Full Information

First Posted
April 29, 2013
Last Updated
September 17, 2018
Sponsor
Karl Neff
Collaborators
University College Dublin
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1. Study Identification

Unique Protocol Identification Number
NCT01847313
Brief Title
The Effect of Glucagon-like-peptide 1 (GLP-1) Receptor Agonism on Diabetic Kidney Disease
Official Title
Phase 3 Study of the Effect of Glucagon-like-peptide 1 (GLP-1) Receptor Agonism on Renal Outcomes in Humans With Diabetic Kidney Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
November 2015 (Actual)
Study Completion Date
November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Karl Neff
Collaborators
University College Dublin

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Diabetic kidney disease (DKD) is a devastating complication of diabetes, that in it's worst form, can lead to early cardiovascular death or kidney failure. A group of medicines used to treat diabetes, glucagon-like-peptide-1 analogues (GLP-1), may be able to protect people with diabetes from DKD by reducing inflammation in the kidney. This study aims to test this theory by studying the effect of GLP-1 on kidney function in people with diabetes. To understand how GLP-1 can affect inflammation, the investigators will give a GLP-1 treatment (Liraglutide) to people with DKD and monitor the effect on inflammation and kidney function using blood and urine tests. The investigators will compare these results to patients with DKD who do not receive GLP-1 treatment. If GLP-1 proves to be effective in reducing inflammation and improving kidney function, then it could be developed as a viable new treatment for people with DKD, and may significantly reduce the disease burden, or the risk of DKD, in people with diabetes. This would be a major advance in the treatment of DKD.
Detailed Description
A randomised controlled trial for patients with microalbuminuria and type 2 diabetes. Treatment is 0.6mg of liraglutide and is compared to standard care. Treatment duration is 6 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetic Kidney Disease
Keywords
kidney, diabetes, glp-1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Liraglutide
Arm Type
Active Comparator
Arm Description
Liraglutide 0.6 mg daily
Arm Title
Control
Arm Type
No Intervention
Arm Description
Standard diabetes care including renin angiotensin aldosterone system inhibitor or antagonist
Intervention Type
Drug
Intervention Name(s)
Liraglutide
Other Intervention Name(s)
Glucagon like peptide 1 receptor agonist, NN2211
Intervention Description
Daily administration of liraglutide for 6 months
Primary Outcome Measure Information:
Title
MCP-1:Creatinine Ratio in Urine
Description
Spot urine sample for MCP-1 and creatinine
Time Frame
Up to 26 weeks
Secondary Outcome Measure Information:
Title
Urine Albumin:Creatinine Ratio
Description
Spot urine sample for albumin and creatinine
Time Frame
Up to 26 weeks
Title
Urinary Albumin Excretion Rate
Description
Albuminuria as Measured by 24 Hour Albumin Excretion Rate
Time Frame
Up to 26 weeks
Title
sCD163 in Serum
Description
Serum sample for sCD163
Time Frame
Up to 26 weeks
Title
sCD163:Creatinine Ratio in Urine
Description
Spot urine sample for MCP-1 and creatinine
Time Frame
Up to 26 weeks
Other Pre-specified Outcome Measures:
Title
Safety in All Participants as Measured by Adverse Event Rate
Description
Adverse event data collection
Time Frame
Up to 34 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Type 2 diabetes with a HbA1c of 42-75mmol/mol (6-9%DCCT) Male or female aged above 30 years Have a negative pregnancy test at screening (women of child bearing potential only) Body mass index (BMI) of 25kg/m2 or greater On a renin-angiotensin system antagonist, at a stable dose, for at least 8 weeks before inclusion into the study Established microalbuminuria Estimated glomerular filtration rate (eGFR) 30ml/min/1.73m2 or above by Modification of Diet in Renal Disease (MDRD) formula Exclusion Criteria: Patients with any cognitive impediment that preclude the patient from giving free and informed consent Patients on dipeptidyl peptidase 4 inhibitors or thiazolidinedione treatment Patients with stage 4-5 renal disease, defined as an eGFR of 30ml/min/1.73m2 or less Patients who have used a GLP-1 agent in the last 6 months Female patients of child bearing potential who are pregnant, breastfeeding, or unwilling to practice an acceptable barrier and/or hormonal method of contraception or abstinence during participation in the study Previous pancreatitis Hypersensitivity to GLP-1 analogues Proliferative diabetic retinopathy Any other contraindications, as per the SmPC for liraglutide Patients with any other clinical condition or prior therapy that, in the opinion of the investigator, would make the patient unsuitable for the study or unable to comply with the dosing requirements Concurrent treatment with an investigational drug or participation in another clinical trial Use of an investigational drug within 4 weeks or 5 half-lives, whichever is longer, preceding the first dose of investigational medicinal product
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carel le Roux, MBBS PhD
Organizational Affiliation
University College Dublin
Official's Role
Study Director
Facility Information:
Facility Name
St Vincent's Healthcare Group
City
Dublin
ZIP/Postal Code
Dublin 4
Country
Ireland

12. IPD Sharing Statement

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The Effect of Glucagon-like-peptide 1 (GLP-1) Receptor Agonism on Diabetic Kidney Disease

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