Clinical trial NCT01847313: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetic Kidney Disease
Keywords: kidney
diabetes
glp-1
Lead sponsor: University College Dublin
Sponsor class: OTHER
Collaborators: name: University College Dublin
First posted: 2013-05-06
Enrollment: 20
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: MCP-1:Creatinine Ratio in Urine
timeFrame: Up to 26 weeks
Secondary outcomes:
measure: Urine Albumin:Creatinine Ratio
timeFrame: Up to 26 weeks
measure: Urinary Albumin Excretion Rate
timeFrame: Up to 26 weeks
measure: sCD163 in Serum
timeFrame: Up to 26 weeks
measure: sCD163:Creatinine Ratio in Urine
timeFrame: Up to 26 weeks
Other outcomes:
measure: Safety in All Participants as Measured by Adverse Event Rate
timeFrame: Up to 34 weeks
Locations:
city: Dublin
country: Ireland
facility: St Vincent's Healthcare Group
Study officials:
affiliation: University College Dublin
name: Carel le Roux, MBBS PhD
role: STUDY_DIRECTOR
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