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

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ClinicalTrials.gov Identifier: NCT02106104
Recruitment Status : Completed
First Posted : April 8, 2014
Last Update Posted : May 17, 2016
Sponsor:
Information provided by (Responsible Party):
M.H.H. Kramer, VU University Medical Center

Brief 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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Drug: Linagliptin 5 mg QD (N=24) Drug: Glimepiride 1 mg QD (N=24) Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Study Start Date : March 2014
Actual Primary Completion Date : April 2016
Actual Study Completion Date : April 2016

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Amaryl




Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Renal tubular function [ Time Frame: 8 weeks ]
  2. Renal damage, measured by urine biomarkers [ Time Frame: 8 weeks ]
  3. Blood Pressure and Heart Rate [ Time Frame: 8 weeks ]

Other Outcome Measures:
  1. Body anthropometrics: body weight, height, body mass index, waist circumference [ Time Frame: 8 weeks ]
  2. Body fat content [ Time Frame: 8 weeks ]
  3. 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

  4. Cardiac autonomic nervous system function [ Time Frame: 8 weeks ]
  5. Microvascular function [ Time Frame: 8 weeks ]
  6. Arterial stiffness [ Time Frame: 8 weeks ]
  7. Glycemic variables [ Time Frame: 8 weeks ]
    Glycated hemoglobin (HbA1c) and fasting glucose

  8. Lipid spectrum [ Time Frame: 8 weeks ]
  9. DPP4- and ACE activity [ Time Frame: 8 weeks ]


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Ages Eligible for Study:   35 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02106104


Locations
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Netherlands
VU University Medical Center
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
VU University Medical Center
Investigators
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Principal Investigator: Mark Kramer, MD PhD VU University Medical Center

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Responsible Party: M.H.H. Kramer, MD PhD, VU University Medical Center
ClinicalTrials.gov Identifier: NCT02106104     History of Changes
Other Study ID Numbers: DC2013RENALIS
U1111-1143-9518 ( Other Identifier: Universal Trial Number )
2013-002493-47 ( EudraCT Number )
NL47157.029.13 ( Registry Identifier: CCMO )
First Posted: April 8, 2014    Key Record Dates
Last Update Posted: May 17, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by M.H.H. Kramer, VU University Medical Center:
Type 2 diabetes mellitus
Diabetic kidney disease
Diabetic nephropathy
Renoprotection
DPP-4 inhibitors
Linagliptin
SU derivatives
Glimepiride
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Glimepiride
Linagliptin
Dipeptidyl-Peptidase IV Inhibitors
Anti-Arrhythmia Agents
Hypoglycemic Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action