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    The EU Clinical Trials Register currently displays   44241   clinical trials with a EudraCT protocol, of which   7338   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2012-005220-15
    Sponsor's Protocol Code Number:IIS-1-025R-NL_Kamphuisen
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-05-17
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedNetherlands - Competent Authority
    A.2EudraCT number2012-005220-15
    A.3Full title of the trial
    Off taRget Effects of Linagliptin monothErapy on Arterial Stiffness in Early diabetes
    Pleiotrope effecten van Linagliptin monotherapie op arteriële stijfheid bij vroege diabetes
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study on the positive effects of treatment with linagliptin on the arteries of patients with diabetes
    Onderzoek naar de positieve effecten van behandeling met linagliptin op de bloedvaten van patienten met diabetes
    A.3.2Name or abbreviated title of the trial where available
    RELEASE
    RELEAS
    A.4.1Sponsor's protocol code numberIIS-1-025R-NL_Kamphuisen
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorUniversity Medical Center Groningen
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportBoehringer Ingelheim GmbH
    B.4.2CountryGermany
    B.4.1Name of organisation providing supportUniversity Medical Center Groningen (UMCG)
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Medical Center Groningen (UMCG)
    B.5.2Functional name of contact pointD.J. Mulder, project leader
    B.5.3 Address:
    B.5.3.1Street AddressHanzeplein 1
    B.5.3.2Town/ cityGroningen
    B.5.3.3Post code9713GZ
    B.5.3.4CountryNetherlands
    B.5.6E-maild.j.mulder@umcg.nl
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Trajenta
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim International GmbH
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    type 2 diabetes mellitus
    diabetes mellitus type 2
    E.1.1.1Medical condition in easily understood language
    diabetes
    suikerziekte
    E.1.1.2Therapeutic area Diseases [C] - Hormonal diseases [C19]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.1
    E.1.2Level LLT
    E.1.2Classification code 10045252
    E.1.2Term Type II diabetes mellitus without mention of complication
    E.1.2System Organ Class 100000004861
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. To assess whether linagliptin compared with placebo improves arterial stiffness in treatment naïve subjects with type 2 diabetes.
    1. beoordelen of linagliptin in vergelijking met placebo de arteriële stijfheid verbetert bij niet eerder behandelde patiënten met type 2 diabetes.
    E.2.2Secondary objectives of the trial
    2. To assess whether linagliptin compared with placebo improves blood pressure parameters, inflammatory and endothelial
    function markers, albuminuria, and vascular inflammation in treatment naïve subjects with type 2 diabetes.
    3. To determine whether the off-target effects on arterial stiffness blood pressure parameters, inflammatory endothelial function
    markers and vascular inflammation are concordant with changes in glucose parameters, including HbA1c fasting plasma
    glucose, and beta-cell and insulin sensitivity indices.
    2. Beoordelen of linagliptin in vergelijking met placebo de bloeddruk parameters, ontstekings-en endotheelfunctie markers en
    albuminurie bij behandelingsnaïeve patiënten met type 2 diabetes verbetert.
    3. Bepalen of de off-target effecten op arteriële stijfheid, bloeddruk parameters, inflammatoire en endotheelfunctie markers en
    inflammatie van de vaten concordant zijn met veranderingen in glucose parameters, waaronder HbA1c nuchtere plasma
    glucose en beta-cel en insulinegevoeligheid indices
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Men and women, age 30 to 70 years, AND
    - Treatment naïve type 2 diabetes, as defined as the presence of one of the following (American Diabetes Association definition:
    - Fasting plasma glucose ≥ 7.0 mmol/l, OR
    - Random plasma glucose ≥ 11.1 mmol/l, OR
    - HbA1c ≥6,5%
    - Mannen en vrouwen, leeftijd 30 tot 70 jaar, EN
    - Behandelings naïeve type 2 diabetes, gedefinieerd als de aanwezigheid van een van de volgende:
    - Nuchter plasma glucose ≥ 7,0 mmol / l, of
    - Random plasma glucose ≥ 11,1 mmol / l, of
    - HbA1c ≥ 6,5%
    E.4Principal 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
    - 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, tryglicerides >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
    - Huidige of eerder gebruik van de glykemische controle medicijnen
    - Type 1 diabetes
    - Zwangerschapsdiabetes
    - Andere specifieke vormen van diabetes door andere oorzaken
    - Ongecontroleerde hypertensie, gedefinieerd als systolische bloeddruk> 160 of een diastolische bloeddruk> 100 mmHg bij screeningsbezoek
    - Ernstige dyslipidemie, gedefinieerd als de totale cholesterol> 8 mmol / l, tryglicerides> 10 mmol / l HDL-cholesterol <0,6 mmol / l
    - Het huidige gebruik van medicatie voor gewichtsverlies of bariatrische chirurgie in verleden
    - Een voorgeschiedenis van ernstige gastro-intestinale aandoeningen
    - Klinische contra-indicaties voor DPP-4-remmers
    - hart-en vaatziekten, gedefinieerd als een stabiele coronaire hartziekte of acuut coronair syndroom, beroerte of TIA, perifeer arterieel vaatlijden
    - Symptomatisch hartfalen, New York Heart Association (NYHA) klasse II-IV
    - Vrouwen die momenteel zwanger zijn, zwanger willen worden, vrouwen die borstvoeding geven, of vrouwen in de vruchtbare leeftijd zonder adequate anticonceptieve maatregelen
    - Klinisch significante leverziekte of leverfunctie groter dan 3 maal de bovengrens van normaal
    - Bekende verminderde nierfunctie of GFR <30 ml/min/1.73m2
    - Patiënten die wilsonbekwaam zijn en geen toestemming kunnen verlenen
    - Huidige actieve maligniteit of in de afgelopen 6 maanden
    - Gedocumenteerde HIV-infectie
    - Het gebruik van rifampicine
    E.5 End points
    E.5.1Primary end point(s)
    Difference in mean Pulse Wave Velocity (PWV) after 26 weeks between the Linagliptin and placebo treated group.
    Verschil in gemiddelde Pulse Wave Velocity (PWV) na 26 weken tussen de Linagliptin en placebo behandelde groep.
    E.5.1.1Timepoint(s) of evaluation of this end point
    26 weeks
    26 weken
    E.5.2Secondary end point(s)
    - Central Blood Pressure (CBP) and Augmentation Index (AI) obtained from pulse wave analysis, using Sphygmocor
    - Carotid-(left) radial arterial PWV, using Sphygmocor
    - Body Mass Index (BMI) and Waist-to-Hip ratio
    - 24-hours ambulatory blood pressure measurement (24-ABPM)
    - Urinary albumin/creatinine ratio (mean of 2 separate morning portions (ACR)
    - plasma markers of inflammation ( i.e. high-sensitivity C-reactive protein (hs-CRP); Interleukin-6; TNF-α, serum amyloid-A
    (SAA), myeloperoxidase (MPO))
    - plasma markers of endothelial dysfunction (i.e. vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion
    molecule-1 (sICAM-1), soluble E-selectin, von Willebrand factor, tissue-type plasminogen activator), in vitro stimulated cytokine
    production by peripheral blood mononuclear cells (PBMC)
    - Glycemic indices: fasting glucose (FPG) and 2-hour post OGTT glucose (OGTT), HbA1c, fasting insulin, and derived indices
    (HOMA-β (as a surrogate marker for β –cell function) and HOMA-IR (insulin resistance), Matsuda index (insulin sensitivity)
    - Skin AGE deposition measured as skin autofluorescence using AGE reader and plasma levels of AGEs (N(ε)-(carboxymethyl)
    lysine (CML), N(ε)-(Carboxyethyl) lysine (CEL)
    - Intake of energy, Eating behaviour, and Physical activity
    - Target-to-background ratios (TBRs) (18)F-fluorodeoxyglucose positron emission tomography computed tomography
    coregistration (FDG PET-CT)
    - Centraal Bloeddruk (CBP) en Augmentation Index (AI), verkregen uit pulse wave analyse, met behulp van Sphygmocor
    - Carotis-(links) radiale arteriële PWV, met behulp van Sphygmocor
    - Body Mass Index (BMI) en middel-heup omtrek
    - 24-uurs ambulante bloeddrukmeting (24-ABPM)
    - Urine albumine / creatinine ratio (gemiddelde van 2 aparte ochtend porties (ACR)
    - Plasma markers van ontsteking (C-reactief proteïne (hs-CRP), interleukine-6, TNF-α, serum amyloid-A (SAA),
    myeloperoxidase (MPO))
    - Plasma markers van endotheeldisfunctie (ie vascular cell adhesion molecule-1 (sVCAM-1), oplosbaar intercellular adhesion
    molecule-1 (sICAM-1), oplosbare E-selectine, von Willebrand factor, weefsel-type plasminogeen activator), in vitro
    gestimuleerde cytokine productie door zgn peripheral blood mononuclear cells (PBMC)
    - Glycemische indices: nuchtere glucose (FPG) en 2-uur na OGTT glucose (OGTT), HbA1c, nuchtere insuline, en afgeleide
    indices (HOMA-β (als een surrogaat marker voor β-cel functie) en HOMA-IR (insulineresistentie ), Matsuda-index (de
    gevoeligheid voor insuline)
    - AGE depositie in de huid gemeten als huidautofluorescentie m.b.v. AGE reader en plasma AGEs (N (ε) - (carboxymethyl)
    lysine (CML), N (ε) - (carboxyethyl) lysine (CEL)
    - energie inname, eetgedrag en lichamelijke activiteit
    - Target-to-background ratios (TBRs) (18)F-fluorodeoxyglucose positron emission tomography computed tomography
    coregistration (FDG PET-CT)
    E.5.2.1Timepoint(s) of evaluation of this end point
    4, 26, and 30 weeks
    4, 26 en 30 weken
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    laatste visite, laatste patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state40
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    none
    geen
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2013-05-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-10-23
    P. End of Trial
    P.End of Trial StatusCompleted
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