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

17 maj 2016 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

45

Fas

  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

30 år till 70 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Linagliptin
Linagliptin 5 mg/day + lifestyle advise
one tablet linagliptin 5 mg/day for 26 weeks
Andra namn:
  • Trajenta
  • DPP-4-hämmare
Placebo-jämförare: Placebo
Matching placebo + lifestyle advise
one tablet matching placebo/day for 26 weeks

Vad mäter studien?

Primära resultatmått

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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Secondary vascular study parameters
Tidsram: 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)
Tidsram: 26 weeks
Target-to-background ratios (TBRs) (18)F-fluorodeoxyglucose positron emission tomography computed tomography coregistration (FDG PET-CT)
26 weeks

Andra resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Body Mass Index and Waist-to-Hip ratio
Tidsram: 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
Tidsram: 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
Tidsram: 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
Tidsram: baseline, week 26
baseline, week 26
plasma markers of endothelial dysfunction
Tidsram: baseline, week 26
baseline, week 26
Glycemic indices
Tidsram: 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
Tidsram: 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
Tidsram: baseline, week 26
Intake of energy, Eating behaviour, and Physical activity
baseline, week 26

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Samarbetspartners

Utredare

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

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 mars 2014

Primärt slutförande (Faktisk)

1 januari 2016

Avslutad studie (Faktisk)

1 mars 2016

Studieregistreringsdatum

Först inskickad

9 december 2013

Först inskickad som uppfyllde QC-kriterierna

12 december 2013

Första postat (Uppskatta)

19 december 2013

Uppdateringar av studier

Senaste uppdatering publicerad (Uppskatta)

18 maj 2016

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

17 maj 2016

Senast verifierad

1 maj 2016

Mer information

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