Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Effects of metformin on hepatic free fatty acid metabolism in type 2 diabetes asssessed by positron emission tomography

    Summary
    EudraCT number
    		 2012-000808-16
    Trial protocol
    		 DK  
    Global end of trial date
    30 Jun 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Dec 2020
    First version publication date
    11 Dec 2020
    Other versions
    Summary report(s)
    		 Metformin lipid paper

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    C11palmitatmetformin
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01729156
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Aarhus University Hospital
    Sponsor organisation address
    Palle Juul-Jensens Boulevard 165, Aarhus N, Denmark, 8200
    Public contact
    Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, lars.christian.gormsen@ki.au.dk
    Scientific contact
    Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, 45 78456260, lars.christian.gormsen@ki.au.dk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    01 Aug 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Jun 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    30 Jun 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    It is the general purpose of the trial to investigate whether the positive effects of metformin on blood lipids are caused by improved glycemic control and changes in body composition or if they are caused by direct effects on lipid metabolism. We specifically plan to: - investigate hepatic fatty acid uptake, reesterification and oxidation assessed by positron emission tomography (PET) - investigate the effect of metformin on whole body VLDL-TG oxidation and redeposition in adipose tissue.
    Protection of trial subjects
    All trial subjects were investigated using as low a dose of radio-tracer as technically possible, all biopsies were taken during local anesthesia.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jan 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Denmark: 36
    Worldwide total number of subjects
    36
    EEA total number of subjects
    36
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    26
    From 65 to 84 years
    10
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients and healthy subjects were recruited through newspaper adds and from the outpatient clinic on Aarhus University Hospital

    Pre-assignment
    Screening details
    		 T2D: age > 50 years, body mass index (BMI) <40 kg/m2 and T2D as defined by American Diabetes Association criteria Healthy: age > 50 years, body mass index (BMI) <40 kg/m2 and normal glucose tolerance

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    Randomization to the placebo group or metformin group was performed using random permuted blocks of 4 participants with 1:1 allocation ratio, resulting in 12 participants in the placebo and 12 in the metformin group. Both study participants and investigator were blinded to the allocation until the end of the study

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PLA_
    Arm description
    		 Individuals with type 2 diabetes randomized to PLACEBO
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    2 tablets bi-daily

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1000 mg bi-daily

    Arm title
    		 MET_
    Arm description
    		 Individuals with type 2 diabetes randomized to 1000 mg metformin bi-daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Metformin "Teva"
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg x 2 taken orally bi-daily

    Arm title
    		 CONT
    Arm description
    		 Non-diabetic individuals
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Metformin "Teva"
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    500 mg x 2 taken orally bi-daily

    Number of subjects in period 1
    		PLA_ MET_ CONT
    Started
    12
    12
    12
    Completed
    12
    12
    12

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    PLA_
    Reporting group description
    		 Individuals with type 2 diabetes randomized to PLACEBO

    Reporting group title
    MET_
    Reporting group description
    		 Individuals with type 2 diabetes randomized to 1000 mg metformin bi-daily

    Reporting group title
    CONT
    Reporting group description
    		 Non-diabetic individuals

    Reporting group values
    		 PLA_ MET_ CONT Total
    Number of subjects
    		 12 12 12 36
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 10 7 8 25
        From 65-84 years
    		 2 5 4 11
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 60 ( 5 ) 64 ( 5 ) 62 ( 6 ) -
    Gender categorical
    Units: Subjects
        Female
    		 3 6 6 15
        Male
    		 9 6 6 21

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    PLA_
    Reporting group description
    		 Individuals with type 2 diabetes randomized to PLACEBO

    Reporting group title
    MET_
    Reporting group description
    		 Individuals with type 2 diabetes randomized to 1000 mg metformin bi-daily

    Reporting group title
    CONT
    Reporting group description
    		 Non-diabetic individuals

    Primary: Hepatic fatty acid oxidation

    		 Close Top of page
    End point title
    		 Hepatic fatty acid oxidation
    End point description
    Delta hepatic fatty acid oxidation after three months treatment measured by 11C-palmitate PET
    End point type
    Primary
    End point timeframe
    3 months
    End point values
    		 PLA_ MET_ CONT
    Number of subjects analysed
    9
    8
    10
    Units: micromol/g/minute
        arithmetic mean (standard deviation)
    -0.005 ( 0.032 )
    0.010 ( 0.018 )
    0.005 ( 0.022 )
    Statistical analysis title
    		 ANOVA delta hepatic fatty acid oxidation
    Comparison groups
    PLA_ v MET_ v CONT
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 < 0.05
    Method
    		 ANOVA
    Parameter type
    		 F-value
    Confidence interval

    Primary: Hepatic fatty acid uptake

    		 Close Top of page
    End point title
    		 Hepatic fatty acid uptake
    End point description
    delta hepatic fatty acid uptake after three months treatment
    End point type
    Primary
    End point timeframe
    3 months
    End point values
    		 PLA_ MET_ CONT
    Number of subjects analysed
    9
    8
    10
    Units: micromol/g/min
        arithmetic mean (standard deviation)
    -0.023 ( 0.047 )
    0.020 ( 0.023 )
    0.021 ( 0.053 )
    Attachments
    		 Untitled (Filename: Figure2.jpg)
    Statistical analysis title
    		 Lipid statistics
    Comparison groups
    PLA_ v MET_ v CONT
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 < 0.05
    Method
    		 Mixed models analysis
    Parameter type
    		 Mean difference (net)
    Confidence interval
         sides
    2-sided
         lower limit
    		 -
         upper limit
    		 -

    Primary: Hepatic fatty acid esterification

    		 Close Top of page
    End point title
    		 Hepatic fatty acid esterification
    End point description
    Delta hepatic fatty acid esterification after three months treatment
    End point type
    Primary
    End point timeframe
    3 months
    End point values
    		 PLA_ MET_ CONT
    Number of subjects analysed
    9
    8
    10
    Units: micromol/g/min
        arithmetic mean (standard deviation)
    -0.020 ( 0.029 )
    0.010 ( 0.015 )
    0.015 ( 0.045 )
    Statistical analysis title
    		 ANOVA delta hepatic fatty metabolism
    Comparison groups
    PLA_ v MET_ v CONT
    Number of subjects included in analysis
    27
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 < 0.05
    Method
    		 ANOVA
    Parameter type
    		 F-value
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    3 months
    Adverse event reporting additional description
    Adverse events reported during the trial
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 GCP unit Aarhus
    Dictionary version
    1
    Reporting groups
    Reporting group title
    PLA_
    Reporting group description
    		 Individuals with type 2 diabetes randomized to PLACEBO

    Reporting group title
    MET_
    Reporting group description
    		 Individuals with type 2 diabetes randomized to 1000 mg metformin bi-daily

    Reporting group title
    CONT
    Reporting group description
    		 Non-diabetic individuals

    Serious adverse events
    		 PLA_ MET_ CONT
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 PLA_ MET_ CONT
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    0 / 12 (0.00%)
    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: No trial related non-serious adverse events were recorded

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Only results from primary endpoint are reported - for secondary endpoints please see publications

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/30976851
    http://www.ncbi.nlm.nih.gov/pubmed/29405635
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 06:24:29 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA