Renal Effects of DPP-4 Inhibitor Linagliptin in Type 2 Diabetes (RENALIS)

May 16, 2016 updated by: M.H.H. Kramer, Amsterdam UMC, location VUmc

A Phase 4, Monocenter, Randomized, Double-blind, Comparator-controlled, Parallel-group, Mechanistic Intervention Trial to Assess the Effect of 8-week Treatment With the Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Linagliptin Versus the Sulfonylurea (SU) Derivative Glimepiride on Renal Physiology and Biomarkers in Metformin-treated Patients With Type 2 Diabetes Mellitus (T2DM)

The aim of this study is to detail the (mechanisms underlying the) actions of the DPP-4 inhibitor linagliptin on the renal system in patients with type 2 diabetes mellitus.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Based on preclinical and small-sized studies in non-diabetic individuals, incretin-based therapies, i.e. glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4i), may hold promise in preventing the onset and progression of diabetic kidney disease. However, the potential renoprotective effects of these agents, that are believed to be effectuated "beyond glucose control", have not been sufficiently detailed in human diabetes.

Therefore, the present study aims to explore the mechanistic and clinical effects of DPP-4i on fasting and postprandial renal physiology and biomarkers in patients with type 2 diabetes.

Forty-eight patients with type 2 diabetes will undergo an eight week intervention with linagliptin or glimepiride in order to assess changes in the outcome parameters.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • VU University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients with type 2 diabetes (HbA1c: 6.5-9.0% DCCT or 48-75 mmol/mol IFCC)
  • Metformin monotherapy; using a stable dose for at least 3 months prior to inclusion
  • Both genders (females must be post-menopausal)
  • Caucasian
  • Age: 35-75 years
  • Body Mass Index: >25 kg/m2
  • All patients with previously diagnosed hypertension should use a RAS-interfering agent (angiotensin converting enzyme inhibitor/angiotensin II receptor blocker) for at least 3 months

Exclusion Criteria:

  • Current / chronic use of the following medication: thiazolidinediones, insulin, glucocorticoids, immune suppressants, antimicrobial agents or chemotherapeutics. Subjects on diuretics will only be excluded when these drugs (e.g. hydrochlorothiazide) cannot be stopped for the duration of the study
  • Chronic use of NSAIDs will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications. However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing
  • Pregnancy
  • Frequent occurrence of (confirmed) hypoglycemia (plasma glucose <3.9 mmol/L)
  • Estimated Glomerular Filtration Rate < 60 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)
  • Current urinary tract infection and active nephritis
  • Recent (<6 months) history of cardiovascular disease, including: acute coronary syndrome, chronic heart failure (New York Heart Association grade II-IV), stroke, transient ischemic neurologic disorder
  • Complaints compatible with or established gastroparesis and/or neurogenic bladder
  • Active liver disease
  • History of or actual pancreatic disease
  • History of or actual malignancy (except for basal cell carcinoma)
  • History of or actual severe mental disease
  • Substance abuse (alcohol: defined as >4 units/day; smoking/nicotine: defined as daily smoking/use)
  • Allergy to any of the agents used in the study
  • Inability to understand the study protocol or give informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Linagliptin 5 mg QD (N=24)
Linagliptin 5 mg will be taken orally, once daily for 8 weeks
Drug: Linagliptin 5 mg QD (N=24)
Linagliptin 5 mg will be taken orally, once daily for 8 weeks
Other Names:
  • Trajenta
Active Comparator: Glimepiride 1 mg QD (N=24)
Glimepiride 1 mg will be taken orally, once daily for 8 weeks
Drug: Glimepiride 1 mg QD (N=24)
Glimepiride 1 mg will be taken orally, once daily for 8 weeks
Other Names:
  • Amaryl

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes from baseline following 8-week treatment with linagliptin vs glimepiride on fasting and postprandial renal hemodynamics, measured as GFR / ERPF (determined by inulin/para-aminohippuric-acid clearance)
Time Frame: 8 weeks
8 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Renal tubular function
Time Frame: 8 weeks
8 weeks
Renal damage, measured by urine biomarkers
Time Frame: 8 weeks
8 weeks
Blood Pressure and Heart Rate
Time Frame: 8 weeks
8 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body anthropometrics: body weight, height, body mass index, waist circumference
Time Frame: 8 weeks
8 weeks
Body fat content
Time Frame: 8 weeks
8 weeks
Systemic hemodynamic variables (blood pressure, heart rate, stroke volume, cardiac output/-index, total systemic vascular resistance)
Time Frame: 8 weeks
Derived from non-invasive beat-to-beat finger blood pressure measurements
8 weeks
Cardiac autonomic nervous system function
Time Frame: 8 weeks
8 weeks
Microvascular function
Time Frame: 8 weeks
8 weeks
Arterial stiffness
Time Frame: 8 weeks
8 weeks
Glycemic variables
Time Frame: 8 weeks
Glycated hemoglobin (HbA1c) and fasting glucose
8 weeks
Lipid spectrum
Time Frame: 8 weeks
8 weeks
DPP4- and ACE activity
Time Frame: 8 weeks
8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amsterdam UMC, location VUmc

Investigators

  • Principal Investigator: Mark Kramer, MD PhD, Amsterdam UMC, location VUmc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

April 1, 2016

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

March 28, 2014

First Submitted That Met QC Criteria

April 2, 2014

First Posted (Estimate)

April 8, 2014

Study Record Updates

Last Update Posted (Estimate)

May 17, 2016

Last Update Submitted That Met QC Criteria

May 16, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DC2013RENALIS
  • U1111-1143-9518 (Other Identifier: Universal Trial Number)
  • 2013-002493-47 (EudraCT Number)
  • NL47157.029.13 (Registry Identifier: CCMO)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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