- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg 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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 3
Kontakter og lokationer
Studiesteder
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Groningen, Holland, 9700 RB
- University Medical Center Groningen
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
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
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Linagliptin
Linagliptin 5 mg/day + lifestyle advise
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one tablet linagliptin 5 mg/day for 26 weeks
Andre navne:
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Placebo komparator: Placebo
Matching placebo + lifestyle advise
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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
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baseline, week 26
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Secondary vascular study parameters
Tidsramme: 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)
Tidsramme: 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
|
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
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baseline, week 4, week 26, and 4 weeks after treatment discontinuation (week 30)
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Blood pressure
Tidsramme: 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
Tidsramme: 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
Tidsramme: baseline, week 26
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baseline, week 26
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plasma markers of endothelial dysfunction
Tidsramme: baseline, week 26
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baseline, week 26
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Glycemic indices
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Pieter W Kamphuisen, MD PhD, University Medical Center Groningen
Publikationer og nyttige links
Generelle publikationer
- 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.
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Glukosemetabolismeforstyrrelser
- Metaboliske sygdomme
- Sygdomme i det endokrine system
- Diabetes mellitus
- Diabetes mellitus, type 2
- Hypoglykæmiske midler
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Proteasehæmmere
- Inkretiner
- Linagliptin
- Dipeptidyl-Peptidase IV-hæmmere
Andre undersøgelses-id-numre
- NL43473.042.13
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