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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   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:2018-003121-29
    Sponsor's Protocol Code Number:D20180102
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2019-12-10
    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 ConcernedFrance - ANSM
    A.2EudraCT number2018-003121-29
    A.3Full title of the trial
    Impact of Metformin on Peripheral Arterial Calcification
    in Type 1 Diabetes
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Impact of Metformin on Peripheral Arterial Calcification in Type 1 Diabetes
    Effet de la metformine sur les calcifications artérielles périphériques chez le patient diabétique de type 1
    A.3.2Name or abbreviated title of the trial where available
    IMPACT-1D
    IMPACT-1D
    A.4.1Sponsor's protocol code numberD20180102
    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 SponsorASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
    B.1.3.4CountryFrance
    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 supportMinistère de la santé
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDRCI
    B.5.2Functional name of contact pointSophie Courtial-Destembert
    B.5.3 Address:
    B.5.3.1Street AddressDRCI Hôpital St Louis, 1 av. Claude Vellefaux
    B.5.3.2Town/ cityPARIS
    B.5.3.3Post code75010
    B.5.3.4CountryFrance
    B.5.4Telephone number33140275591
    B.5.5Fax number33144841701
    B.5.6E-mailsophie.courtial-destembert@aphp.fr
    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 METFORMINE ARROW LAB 1000 mg, comprimé pelliculé sécable
    D.2.1.1.2Name of the Marketing Authorisation holderARROW GENERIQUES
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.1Product nameMETFORMINE ARROW LAB® 1000 mg
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMETFORMIN
    D.3.9.1CAS number 657-24-9
    D.3.9.4EV Substance CodeSUB08831MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000
    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
    Vascular calcification and type 1 diabetes
    calcification artérielle et diabète de type 1
    E.1.1.1Medical condition in easily understood language
    vascular disease type 1 diabetes
    problème vasculaire et diabète de type 1
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To show that metformin, patients with type 1 diabetes but without chronic kidney disease, is able to slow below- knee arterial calcification
    montrer que la metformine, chez les patients diabétiques de type 1 sans MRC, est capable de ralentir la calcification artérielle des jambes
    E.2.2Secondary objectives of the trial
    1. To show that metformin, in patients with type 1 diabetes but without CKD, is able to slow below-knee arterial occlusive disease.
    2. To show that metformin, in patients with type 1 diabetes but without CKD, is able to improve ankle and toe brachial indexes.
    3. To show that metformin, in patients with type 1 diabetes but without CKD, is able to improve pulse wave velocity.
    4. To show that metformin, in patients with type 1 diabetes but without chronic kidney disease, is able to slow coronary arterial calcification.
    5. To conduct a subgroup analysis for the primary outcome to evaluate whether the effect of metformin on the difference of below-knee arterial calcification score evaluated by CT-scan at T0 and T2years varies according to initial below-knee arterial calcification score (≤ versus >400).
    1. montrer que la metformine, chez les patients atteints de diabète de type 1 mais sans MRC, est capable de ralentir l’artériopathie chronique oblitérante des membres inférieurs en dessous du genou.

    2. montrer que la metformine, chez les patients diabétiques de type 1 sans MRC, est capable d'améliorer les index des pressions systoliques (IPS) à la cheville et à l'orteil.

    3. montrer que la metformine, chez les patients diabétiques de type 1 sans MRC, est capable d'améliorer la vitesse des ondes du pouls.

    4. montrer que la metformine, chez les patients diabétiques de type 1 sans MRC, est capable de ralentir la calcification artérielle coronaire.

    5. effectuer une analyse de sous-groupe pour l'objectif principal afin de déterminer si l'effet de la metformine sur la différence du score de calcification artérielle sous le genou évalué par tomodensitométrie à T0 et à T2 ans varie en fonction du score de calcification artérielle sous le genou à l'inclusion (≤ versus > 400).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Type 1 diabetes
    - Women and Men ≥ 18 years old and ≤ 80 years old with:

    *Complications:
    -diabetic retinopathy
    and/or
    -nephropathy (with creatinine clearance ≥ 60 mL/mn) and/or
    -neuropathy
    and/or
    -peripheral arterial occlusive disease
    and/or
    -cardiopathy
    and/or
    -stroke

    and/or

    *cardiovascular risk factors
    - hypertension
    and/or
    - dyslipidemia (HDL < 0.35g/L or LDL > 1.9g/L or treated dyslipidemia)
    and/or
    - tobacco use (old or active smoking greater than 5 pack years)

    and/or

    *Diabetes duration >20 years

    - For women in childbearing age, effective contraception during the whole trial
    - Signed written informed consent
    - Affiliation of a social security regime (patient with AME cannot be included)
    - diabète de type 1
    - femme ou homme âgé de ≥ 18 ans et ≤ 80 ans présentant :

    * les complications suivantes :
    - une rétinopathie diabétique
    et/ou
    - une néphropathie (avec une clairance de la créatinine ≥ 60 mL/mn)
    et/ou
    - une neuropathie
    et/ou
    - une maladie occlusive artérielle périphérique
    et/ou
    - une cardiopathie
    et/ou
    - un AVC

    et/ou

    * des facteurs de risques cardiovasculaires :
    - hypertension
    et/ou
    - dyslipidémie (HDL < 0,35 g/L or LDL > 1,9 g/L ou dyslipidémie traitée)
    et/ou
    - tabagisme (ancien ou actif, supérieur à 5 paquets-années)

    et/ou

    * un diabète depuis plus de 20 ans

    - pour les femmes en âge de procréer, une contraception efficace pendant toute la durée de l'essai
    - consentement éclairé écrit et signé
    - affiliation à un régime de sécurité sociale (hors AME)
    E.4Principal exclusion criteria
    - Creatinine clearance of less than 3 months <60 mL/mn (MDRD) at the inclusion time
    - Known metformin contra-indication:
    • severe liver insufficiency –CHILD B or C
    • heart failure (FEVG<45%) or
    • history of pulmonary oedema, respiratory insufficiency with history of acute respiratory failure or patients receiving oxygen therapy
    • chronic ethylism
    • lactic acidosis
    - Known hypersensitivity to metformin or to any of its excipients or placebo excipients (lactose)
    - Indication or history of lower limb angioplasty (with stenting) and/or bypass
    - Previous treatment with metformin (within 3 months prior to inclusion)
    - HbA1c of less than 3 months >11%
    - Chronic inflammatory disease or chronic immune-suppressive drugs intake
    - Participation in an another interventional trial (Jardé 1 and 2) or in the exclusion period of any other interventional study
    - Pregnancy woman (confirmed by a sanguine beta-HCG test) or breastfeeding woman
    - Patient under legal protection measure (tutorship or curatorship) or deprived of freedom or under measure of safety
    - Unable to consent
    - clairance de la créatinine datant de moins de 3 mois < 60 mL/mn (MDRD) au moment de l'inclusion
    - contre-indication à la metformine connue :
    • insuffisance hépatique grave - CHILD B ou C
    • insuffisance cardiaque (FEVG < 45%) ou
    • antécédent d'œdème pulmonaire, insuffisance respiratoire avec antécédent d'insuffisance respiratoire aiguë ou patient sous oxygénothérapie
    • éthylisme chronique
    • acidose lactique

    - sensibilité connue à la metformine ou à l'un de ses excipients ou à l'un des excipients du placebo (lactose)
    - indication ou antécédent d'angioplastie des membres inférieurs (avec endoprothèse) et/ou de pontage
    - traitement antérieur par metformine (dans les 3 mois précédant l'inclusion)
    - HbA1c datant de moins de 3 mois > 11%
    - maladie inflammatoire chronique ou prise chronique de médicaments immunosuppresseurs
    - participation à un autre essai interventionnel (Jardé 1 et 2) ou patient se trouvant dans la période d'exclusion d'une autre étude interventionnelle
    - femme enceinte (confirmée par un test beta-HCG urinaire et sanguin) ou femme allaitante
    - patient sous protection juridique (tutelle ou curatelle) ou privé de liberté ou sous mesure de sureté
    - patient incapable de consentir
    E.5 End points
    E.5.1Primary end point(s)
    Difference between below-knee arterial calcification score evaluated by CT-scan at T0 and T2years in type 1 diabetic patients treated or not with metformin.
    différence entre le score de calcification artérielle en dessous du genou évalué par tomodensitométrie à T0 et à T2 ans chez les patients diabétiques de type 1 traités ou non par metformine
    E.5.1.1Timepoint(s) of evaluation of this end point
    2 years
    2 ans
    E.5.2Secondary end point(s)
    1. Difference between below-knee arterial ultrasonographic occlusion score at T0 and T2years in type 1 diabetic patients supplemented or not with metformin.
    2. Difference between ankle and toe brachial indexes at T0 and T2years in type 1 diabetic patients supplemented or not with metformin.
    3. Difference between pulse wave velocity at T0 and T2 years in type 1 diabetic patients supplemented or not with metformin.
    4. Difference between coronary calcification score evaluated by CT-scan at T0 and T2years in type 1 diabetic patients treated or not with metformin.
    5. Difference between below-knee arterial calcification score progression between T0 and T2years in type 1 diabetic patients treated or not with metformin and with initial below-knee arterial calcification score ≤ and >400.
    1. différence entre le score d'occlusion échographique artérielle mesuré en dessous du genou à T0 et à T2 ans chez les patients diabétiques de type 1 recevant ou non de la metformine.

    2. différence entre les index de pression systolique (IPS) à la cheville et à l'orteil à T0 et à T2 ans chez les patients diabétiques de type 1 recevant ou non de la metformine.

    3. différence entre la vitesse de l'onde de pouls à T0 et à T2 ans chez les patients diabétiques de type 1 recevant ou non de la metformine.

    4. différence entre le score de calcification coronaire évalué par tomodensitométrie à T0 et à T2 ans chez des patients diabétiques de type 1 traités ou non par metformine.

    5. différence entre la progression du score de calcification artérielle sous le genou entre T0 et T2 ans chez les patients diabétiques de type 1 traités par metformine et dont le score de calcification artérielle sous le genou à l'inclusion est ≤ ou > 400.
    E.5.2.1Timepoint(s) of evaluation of this end point
    2 years
    2 ans
    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 Yes
    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 Yes
    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 No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    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 Yes
    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
    Last visit of the last subject
    dernière visite du dernier patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months44
    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: 200
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state230
    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
    Aucun
    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 Decision2020-01-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-04
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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