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- Essai clinique NCT02015299
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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
Type d'étude
Inscription (Réel)
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
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Groningen, Pays-Bas, 9700 RB
- University Medical Center Groningen
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
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
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
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Expérimental: Linagliptin
Linagliptin 5 mg/day + lifestyle advise
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one tablet linagliptin 5 mg/day for 26 weeks
Autres noms:
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Comparateur placebo: Placebo
Matching placebo + lifestyle advise
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one tablet matching placebo/day for 26 weeks
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
|
change from baseline carotid-(right) femoral arterial Pulse Wave Velocity (PWV) at 26 weeks
Délai: baseline, week 26
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baseline, week 26
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Secondary vascular study parameters
Délai: 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)
Délai: 26 weeks
|
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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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Body Mass Index and Waist-to-Hip ratio
Délai: 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)
|
|
Blood pressure
Délai: 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
Délai: baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
|
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
Délai: baseline, week 26
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baseline, week 26
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plasma markers of endothelial dysfunction
Délai: baseline, week 26
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baseline, week 26
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Glycemic indices
Délai: 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
Délai: 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
Délai: 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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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Pieter W Kamphuisen, MD PhD, University Medical Center Groningen
Publications et liens utiles
Publications générales
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Troubles du métabolisme du glucose
- Maladies métaboliques
- Maladies du système endocrinien
- Diabète sucré
- Diabète sucré, Type 2
- Agents hypoglycémiants
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Inhibiteurs d'enzymes
- Les hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Inhibiteurs de protéase
- Incrétines
- Linagliptine
- Inhibiteurs de dipeptidyl-peptidase IV
Autres numéros d'identification d'étude
- NL43473.042.13
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