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

Type 2 Diabetes Clinical Trial

— RENALIS  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02106104
• Other study ID #: DC2013RENALIS
• Secondary ID: U1111-1143-95182
• Status: Completed
• Phase: Phase 4
• First received: March 28, 2014
• Last updated: May 16, 2016
• Start date: March 2014
• Est. completion date: April 2016

Study information

• Verified date: May 2016
• Source: VU University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Linagliptin 5 mg QD (N=24)
Linagliptin 5 mg will be taken orally, once daily for 8 weeks
• Glimepiride 1 mg QD (N=24)
Glimepiride 1 mg will be taken orally, once daily for 8 weeks

Locations

Country	Name	City	State
Netherlands	VU University Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
VU University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Body anthropometrics: body weight, height, body mass index, waist circumference		8 weeks	No
Other	Body fat content		8 weeks	No
Other	Systemic hemodynamic variables (blood pressure, heart rate, stroke volume, cardiac output/-index, total systemic vascular resistance)	Derived from non-invasive beat-to-beat finger blood pressure measurements	8 weeks	No
Other	Cardiac autonomic nervous system function		8 weeks	No
Other	Microvascular function		8 weeks	No
Other	Arterial stiffness		8 weeks	No
Other	Glycemic variables	Glycated hemoglobin (HbA1c) and fasting glucose	8 weeks	No
Other	Lipid spectrum		8 weeks	No
Other	DPP4- and ACE activity		8 weeks	No
Primary	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)		8 weeks	No
Secondary	Renal tubular function		8 weeks	No
Secondary	Renal damage, measured by urine biomarkers		8 weeks	No
Secondary	Blood Pressure and Heart Rate		8 weeks	No