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Off taRget Effects of Linagliptin monothErapy on Arterial Stiffness in Early Diabetes (RELEASE)
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.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 3
Contacten en locaties
Studie Locaties
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Groningen, Nederland, 9700 RB
- University Medical Center Groningen
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verviervoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Linagliptin
Linagliptin 5 mg/day + lifestyle advise
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one tablet linagliptin 5 mg/day for 26 weeks
Andere namen:
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Placebo-vergelijker: Placebo
Matching placebo + lifestyle advise
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one tablet matching placebo/day for 26 weeks
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
|---|---|
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change from baseline carotid-(right) femoral arterial Pulse Wave Velocity (PWV) at 26 weeks
Tijdsspanne: baseline, week 26
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baseline, week 26
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Secondary vascular study parameters
Tijdsspanne: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Subclinical vascular inflammation (FDG PET-CT)
Tijdsspanne: 26 weeks
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Target-to-background ratios (TBRs) (18)F-fluorodeoxyglucose positron emission tomography computed tomography coregistration (FDG PET-CT)
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26 weeks
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Andere uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Body Mass Index and Waist-to-Hip ratio
Tijdsspanne: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Body Mass Index and Waist-to-Hip ratio
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Blood pressure
Tijdsspanne: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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24-hours ambulatory blood pressure measurement (24-ABPM)
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Advanced glycation end products
Tijdsspanne: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Skin AGE deposition measured and plasma levels of AGEs
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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plasma markers of inflammation
Tijdsspanne: baseline, week 26
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baseline, week 26
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plasma markers of endothelial dysfunction
Tijdsspanne: baseline, week 26
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baseline, week 26
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Glycemic indices
Tijdsspanne: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Fasting glucose (FPG) and 2-hour post OGTT glucose (OGTT), HbA1c
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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albuminuria
Tijdsspanne: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Urinary albumin/creatinine ratio
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Lifestyle
Tijdsspanne: baseline, week 26
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Intake of energy, Eating behaviour, and Physical activity
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baseline, week 26
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Medewerkers en onderzoekers
Sponsor
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Pieter W Kamphuisen, MD PhD, University Medical Center Groningen
Publicaties en nuttige links
Algemene publicaties
- 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.
- 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.
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Glucosemetabolismestoornissen
- Metabole ziekten
- Endocriene systeemziekten
- Suikerziekte
- Diabetes mellitus, type 2
- Hypoglycemische middelen
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Hormonen
- Hormonen, hormoonvervangers en hormoonantagonisten
- Proteaseremmers
- Incretines
- Linagliptine
- Dipeptidyl-peptidase IV-remmers
Andere studie-ID-nummers
- NL43473.042.13
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