NCT03433248

Brief Summary

The current study aims to explore the clinical effects and mechanistics of mono- and combination therapy with SGLT-2 inhibitor empagliflozin and DPP-4 inhibitor linagliptin on renal physiology and biomarkers in metformin-treated T2DM patients.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
66

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 9, 2017

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

November 22, 2017

Completed
3 months until next milestone

First Posted

Study publicly available on registry

February 14, 2018

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2021

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2022

Completed
Last Updated

January 14, 2022

Status Verified

January 1, 2022

Enrollment Period

3.6 years

First QC Date

November 22, 2017

Last Update Submit

January 13, 2022

Conditions

Type2 Diabetes

Keywords

Type 2 diabetes mellitusDiabetic kidney diseaseDiabetic nephropathyRenoprotectionSGLT2 inhibitorEmpagliflozinDPP-4 inhibitorLinagliptinSU derivativeGliclazide

Outcome Measures

Primary Outcomes (2)

  • GFR

    Changes from baseline following 16-week treatment on renal hemodynamics in both the fasting and postprandial state, measured as GFR (determined by the inulin-clearance technique)

    16 weeks

  • GFR

    Changes from baseline following 8-week treatment on renal hemodynamics in both the fasting and postprandial state, measured as GFR (determined by the inulin-clearance technique)

    8 weeks

Secondary Outcomes (14)

  • Renal tubular function

    16 weeks

  • Renal tubular function

    8 weeks

  • Renal Damage

    16 weeks

  • Renal Damage

    10 weeks

  • Renal Damage

    8 weeks

  • +9 more secondary outcomes

Other Outcomes (60)

  • Body anthropometrics: Body mass index

    16 weeks

  • Body anthropometrics: Body mass index

    8 weeks

  • Body anthropometrics: Body weight

    16 weeks

  • +57 more other outcomes

Study Arms (3)

EMPA/LINA 10/5 mg QD (n=22)

EXPERIMENTAL

8w EMPA followed by 8w EMPA/LINA 10/5 mg QD (n=22)

Drug: EMPA/LINA 10/5 mg QD (n=22)Drug: LINA/EMPA 5/10 mg QD (N=22)

LINA/EMPA 5/10 mg QD (N=22)

EXPERIMENTAL

8w LINA followed by LINA/EMPA 5/10 mg QD (N=22)

Drug: EMPA/LINA 10/5 mg QD (n=22)Drug: LINA/EMPA 5/10 mg QD (N=22)

Gliclazide 30 mg QD/BID (N=22)

ACTIVE COMPARATOR

8w Gliclazide 30 mg QD, followed by 8w Gliclazide BID (N=22)

Drug: Gliclazide 30 mg QD/BID (N=22)

Interventions

EMPA/LINA 10/5 mg QD (n=22)DRUG

Once daily treatment with oral empagliflozin (Jardiance) 10 mg Once daily treatment with oral linagliptin (Tradjenta) 5 mg

Also known as: Jardiance, Tradjenta
EMPA/LINA 10/5 mg QD (n=22)LINA/EMPA 5/10 mg QD (N=22)
LINA/EMPA 5/10 mg QD (N=22)DRUG

Once daily treatment with oral linagliptin (Tradjenta) 5 mg Once daily treatment with oral empagliflozin (Jardiance) 10 mg

Also known as: Tradjenta, Jardiance
EMPA/LINA 10/5 mg QD (n=22)LINA/EMPA 5/10 mg QD (N=22)
Gliclazide 30 mg QD/BID (N=22)DRUG

Once daily or twice daily treatment with oral glicazide MR 30mg

Also known as: Gliclazide Sandoz
Gliclazide 30 mg QD/BID (N=22)

Eligibility Criteria

Age35 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Caucasian\*
  • Both genders (females must be post-menopausal; no menses \>1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as \>31 U/L)
  • Age: 35 - 75 years
  • BMI: \>25 kg/m2
  • HbA1c: 7.0 - 9.5% Diabetes Control and Complications Trial (DCCT) or 53 - 80 mmol/mol International Federation of Clinical Chemistry (IFCC)
  • Metformin monotherapy
  • Combination of metformin and low-dose SU derivative\*\*
  • Hypertension should be controlled, i.e. ≤140/90 mmHg, and treated with an ACE-I or ARB (unless prevented by adverse effect) for at least 3 months.
  • Albuminuria should be treated with a RAAS-interfering agent (ACE-I or ARB) for at least 3 months.
  • Written informed consent

You may not qualify if:

  • Estimated GFR \<45 mL/min/1.73m2 (determined by the Modification of Diet in Renal Disease (MDRD) study equation)
  • Hemoglobin level \< 7.0 mmol/L
  • Current urinary tract infection and active nephritis
  • History of unstable or rapidly progressing renal disease
  • Macroalbuminuria; defined as ACR of \>300 mg/g.
  • Current/chronic use of the following medication: thiazolidinediones, sulfonylurea derivatives, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitor, oral glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MOAIs).
  • Patients on diuretics will only be excluded when these drugs cannot be stopped 3 months prior randomization and for the duration of the study.
  • Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, head-ache or back ache). However, no such drugs can be taken within a time-frame of 2 weeks prior to renal-testing
  • Pregnancy
  • History of or actual severe mental disease
  • History of or actual severe somatic disease (e.g. systemic disease)
  • History of or actual malignancy (except basal cell carcinoma)
  • History of or actual pancreatic disease
  • (Unstable) thyroid disease
  • Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) \>3x upper limit of normal (ULN)
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

VU University Medical Center

Amsterdam, North Holland, 1081HV, Netherlands

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetic Nephropathies

Interventions

empagliflozinLinagliptinGliclazide

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesDiabetes Complications

Intervention Hierarchy (Ancestors)

PurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsQuinazolinesBenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsSulfonylurea CompoundsUreaBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur Compounds

Study Officials

  • Mark HH Kramer, MD PhD

    Amsterdam UMC, location VUmc

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Head of the Internal Medicine department

Study Record Dates

First Submitted

November 22, 2017

First Posted

February 14, 2018

Study Start

November 9, 2017

Primary Completion

June 1, 2021

Study Completion

September 1, 2022

Last Updated

January 14, 2022

Record last verified: 2022-01

Data Sharing

IPD Sharing
Will not share

Locations

NL(1)