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Off taRget Effects of Linagliptin monothErapy on Arterial Stiffness in Early Diabetes (RELEASE)

17. maj 2016 opdateret af: dr. DJ Mulder

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.

Studieoversigt

Status

Afsluttet

Detaljeret beskrivelse

Patients with type 2 diabetes mellitus (T2DM) are at increased risk for developing premature macrovascular complications. The process of irreversible subclinical damage to the vasculature already starts during its preceding stages. At diagnosis, patients with T2DM already have evidence of subclinical vascular damage. Recent trials have shown no benefit of glucose lowering therapy when started later in the course of the disease, implicating that early interventions could be more effective in preventing macrovascular complications. Dipeptidyl peptidase (DPP)-4 inhibitors are oral antidiabetic drugs that increase the action of the naturally gut hormone glucagon-like peptide-1 (GLP-1), leading to improvement of postprandial insulin secretion, without hypoglycaemia or weight gain. DPP4 inhibitors improve beta-cell function and insulin resistance. More importantly, off-target effects on adipose tissue inflammation, liver steatosis and atherosclerotic plaques have been extensively documented in animal studies. Furthermore, DDP4 inhibitors improve the cardiovascular risk profile in small clinical studies. Based on these considerations the investigators hypothesize that early therapy with the DPP4 inhibitor linagliptin in subjects with type 2 diabetes will lead to beneficial effects on arterial stiffness, blood pressure and inflammatory markers independent of its effects on glycemic control.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

45

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

      • Groningen, Holland, 9700 RB
        • University Medical Center Groningen

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

30 år til 70 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Current active malignancy or in the previous 6 months
  • Documented HIV infection
  • Use of rifampicin

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Linagliptin
Linagliptin 5 mg/day + lifestyle advise
one tablet linagliptin 5 mg/day for 26 weeks
Andre navne:
  • Trajenta
  • DPP-4 hæmmer
Placebo komparator: Placebo
Matching placebo + lifestyle advise
one tablet matching placebo/day for 26 weeks

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Tidsramme
change from baseline carotid-(right) femoral arterial Pulse Wave Velocity (PWV) at 26 weeks
Tidsramme: baseline, week 26
baseline, week 26

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Secondary vascular study parameters
Tidsramme: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
  • Central Blood Pressure (CBP) and Augmentation Index (AI) obtained from pulse wave analysis, using Sphygmocor
  • Carotid-(left) radial arterial PWV, using Sphygmocor
baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
Subclinical vascular inflammation (FDG PET-CT)
Tidsramme: 26 weeks
Target-to-background ratios (TBRs) (18)F-fluorodeoxyglucose positron emission tomography computed tomography coregistration (FDG PET-CT)
26 weeks

Andre resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Body Mass Index and Waist-to-Hip ratio
Tidsramme: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
Body Mass Index and Waist-to-Hip ratio
baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
Blood pressure
Tidsramme: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
24-hours ambulatory blood pressure measurement (24-ABPM)
baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
Advanced glycation end products
Tidsramme: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
Skin AGE deposition measured and plasma levels of AGEs
baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
plasma markers of inflammation
Tidsramme: baseline, week 26
baseline, week 26
plasma markers of endothelial dysfunction
Tidsramme: baseline, week 26
baseline, week 26
Glycemic indices
Tidsramme: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
Fasting glucose (FPG) and 2-hour post OGTT glucose (OGTT), HbA1c
baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
albuminuria
Tidsramme: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
Urinary albumin/creatinine ratio
baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
Lifestyle
Tidsramme: baseline, week 26
Intake of energy, Eating behaviour, and Physical activity
baseline, week 26

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Samarbejdspartnere

Efterforskere

  • Ledende efterforsker: Pieter W Kamphuisen, MD PhD, University Medical Center Groningen

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. marts 2014

Primær færdiggørelse (Faktiske)

1. januar 2016

Studieafslutning (Faktiske)

1. marts 2016

Datoer for studieregistrering

Først indsendt

9. december 2013

Først indsendt, der opfyldte QC-kriterier

12. december 2013

Først opslået (Skøn)

19. december 2013

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

18. maj 2016

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

17. maj 2016

Sidst verificeret

1. maj 2016

Mere information

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Type 2 diabetes mellitus

Kliniske forsøg med Linagliptin

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