- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning 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.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 3
Kontakter och platser
Studieorter
-
-
-
Groningen, Nederländerna, 9700 RB
- University Medical Center Groningen
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
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
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:
|
|
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)
|
|
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
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Pieter W Kamphuisen, MD PhD, University Medical Center Groningen
Publikationer och användbara länkar
Allmänna 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.
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Störningar i glukosmetabolism
- Metaboliska sjukdomar
- Sjukdomar i det endokrina systemet
- Diabetes mellitus
- Diabetes mellitus, typ 2
- Hypoglykemiska medel
- Läkemedels fysiologiska effekter
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Hormoner
- Hormoner, hormonsubstitut och hormonantagonister
- Proteashämmare
- Inkretiner
- Linagliptin
- Dipeptidyl-Peptidas IV-hämmare
Andra studie-ID-nummer
- NL43473.042.13
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .