NCT02015299

Brief Summary

Diabetes is associated with an increased risk for developing premature macrovascular complications. The process of irreversible subclinical damage to the vasculature already starts during its preceding stages. Dipeptidyl peptidase (DPP)-4 inhibitors have been shown to attenuate vascular damage in preclinical studies. Off-target effects on adipose tissue inflammation, liver steatosis and atherosclerotic plaques have been extensively documented in animal studies. Based on these considerations the investigators hypothesize that early therapy with the DPP4 inhibitor linagliptin in subjects with treatment naive type 2 diabetes will lead to beneficial effects on arterial stiffness as measured by pulse wave velocity.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
45

participants targeted

Target at below P25 for phase_3 type-2-diabetes-mellitus

Timeline
Completed

Started Mar 2014

Typical duration for phase_3 type-2-diabetes-mellitus

Geographic Reach
1 country

1 active site

Status
completed

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

First Submitted

Initial submission to the registry

December 9, 2013

Completed
10 days until next milestone

First Posted

Study publicly available on registry

December 19, 2013

Completed
2 months until next milestone

Study Start

First participant enrolled

March 1, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2016

Completed
Last Updated

May 18, 2016

Status Verified

May 1, 2016

Enrollment Period

1.8 years

First QC Date

December 9, 2013

Last Update Submit

May 17, 2016

Conditions

Type 2 Diabetes Mellitus

Keywords

DiabetesPulse Wave VelocityDipeptidyl peptidase (DPP)-4 inhibitorsLinagliptinArterial StiffnessSubclinical arterial inflammation

Outcome Measures

Primary Outcomes (1)

  • change from baseline carotid-(right) femoral arterial Pulse Wave Velocity (PWV) at 26 weeks

    baseline, week 26

Secondary Outcomes (2)

  • Secondary vascular study parameters

    baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)

  • Subclinical vascular inflammation (FDG PET-CT)

    26 weeks

Other Outcomes (8)

  • Body Mass Index and Waist-to-Hip ratio

    baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)

  • Blood pressure

    baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)

  • Advanced glycation end products

    baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)

  • +5 more other outcomes

Study Arms (2)

Linagliptin

EXPERIMENTAL

Linagliptin 5 mg/day + lifestyle advise

Drug: Linagliptin

Placebo

PLACEBO COMPARATOR

Matching placebo + lifestyle advise

Drug: placebo

Interventions

LinagliptinDRUG

one tablet linagliptin 5 mg/day for 26 weeks

Also known as: Trajenta, DPP-4 inhibitor
Linagliptin
placeboDRUG

one tablet matching placebo/day for 26 weeks

Placebo

Eligibility Criteria

Age30 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men and women, age 30 to 70 years, AND
  • Treatment naïve type 2 diabetes, as defined as t
  • Fasting plasma glucose ≥ 7.0 mmol/l, OR
  • Random plasma glucose ≥ 11.1 mmol/l, OR
  • HbA1c ≥6,5%
  • Written informed consent
  • Assessable Pulse Wave Velocity measurement at screening

You may not qualify if:

  • Current or previous use of glycemic control medications
  • Type 1 diabetes
  • Gestational diabetes mellitus
  • Other specific types of diabetes due to other causes, e.g., genetic defects in β-cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis), and drug- or chemical-induced (such as in the treatment of HIV/AIDS or after organ transplantation)
  • Uncontrolled hypertension, defined as systolic blood pressure \>160 or a diastolic blood pressure \>100 mmHg at screening visit
  • Severe dyslipidemia indicating primary dyslipidemia, defined as total cholesterol \>8 mmol/l, triglycerides \>10 mmol/l of high density lipoprotein cholesterol \<0.6 mmol/l
  • Current use of weight loss medication or previous weight loss surgery
  • History of severe gastrointestinal disease
  • Clinical contraindications to DPP4-inhibitors
  • Previous cardiovascular disease, defined as stable coronary artery disease or acute coronary syndrome, stroke or transient ischemic attack, peripheral artery disease
  • Symptomatic heart failure, New York Heart Association (NYHA) class II-IV
  • Women who are currently pregnant,planning to become pregnant,breastfeeding women, or women with child bearing potential not using appropriate contraceptive measures
  • Clinically significant liver disease or hepatic function greater than 3 times upper limit of normal
  • Known impaired renal function or eGFR \<30 ml/min/1.73m2
  • Patients who are mentally incompetent and cannot sign a Patient Informed Consent
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Medical Center Groningen

Groningen, Provincie Groningen, 9700 RB, Netherlands

Location

Related Publications (2)

  • Reijrink M, de Boer SA, Spoor DS, Lefrandt JD, Lambers Heerspink HJ, Boellaard R, Greuter MJ, Borra RJH, Hillebrands JL, Slart RHJA, Mulder DJ. Visceral adipose tissue volume is associated with premature atherosclerosis in early type 2 diabetes mellitus independent of traditional risk factors. Atherosclerosis. 2019 Nov;290:87-93. doi: 10.1016/j.atherosclerosis.2019.09.016. Epub 2019 Sep 25.

    PMID: 31604171DERIVED

  • de Boer SA, Hovinga-de Boer MC, Heerspink HJ, Lefrandt JD, van Roon AM, Lutgers HL, Glaudemans AW, Kamphuisen PW, Slart RH, Mulder DJ. Arterial Stiffness Is Positively Associated With 18F-fluorodeoxyglucose Positron Emission Tomography-Assessed Subclinical Vascular Inflammation in People With Early Type 2 Diabetes. Diabetes Care. 2016 Aug;39(8):1440-7. doi: 10.2337/dc16-0327. Epub 2016 Jun 8.

    PMID: 27281773DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2Diabetes Mellitus

Interventions

LinagliptinDipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

PurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsQuinazolinesProtease InhibitorsEnzyme InhibitorsMolecular Mechanisms of Pharmacological ActionPharmacologic ActionsChemical Actions and UsesHypoglycemic AgentsPhysiological Effects of Drugs

Study Officials

  • Pieter W Kamphuisen, MD PhD

    University Medical Center Groningen

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
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
MD, PhD

Study Record Dates

First Submitted

December 9, 2013

First Posted

December 19, 2013

Study Start

March 1, 2014

Primary Completion

January 1, 2016

Study Completion

March 1, 2016

Last Updated

May 18, 2016

Record last verified: 2016-05

Locations

NL(1)