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    Clinical Trial Results:
    The control of brain networks after traumatic brain injury: a neuroimaging and neuropsychological study of dopamine and cognition

    Summary
    EudraCT number
    		 2013-004244-37
    Trial protocol
    		 GB  
    Global end of trial date
    29 Sep 2016

    Results information
    Results version number
    		 v2(current)
    This version publication date
    18 Dec 2019
    First version publication date
    15 Nov 2018
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Need to correct the sponsor information.
    Summary report(s)
    		 TBI Dopamine CSR

    Trial information

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    Trial identification
    Sponsor protocol code
    13HH1824
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Imperial College London
    Sponsor organisation address
    South Kensington Campus, London, United Kingdom, SW7 2AZ
    Public contact
    Youssouf, Imperial College London, +44 0203 311 0213, nabila.youssouf@imperial.ac.uk
    Scientific contact
    Youssouf, Imperial College London, +44 0203 311 0213, nabila.youssouf@imperial.ac.uk
    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
    18 Sep 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    29 Sep 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Sep 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    1. To investigate the relationship between dopamine levels (a chemical in the brain which modulates brain functions) in the brain and its impact on cognition in patients who have suffered a traumatic brain injury.
    Protection of trial subjects
    No specific measures were implemented to protect participants, but adverse events were closely monitored and participants were free to withdraw at any time.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Feb 2014
    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
    United Kingdom: 46
    Worldwide total number of subjects
    46
    EEA total number of subjects
    46
    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)
    46
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 158 TBI participants were screened. 62 chose not to participate and 50 met one or more of the exclusion criteria.

    Period 1
    Period 1 title
    Baseline (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo First
    Arm description
    		 participants in this arm received placebo first.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    As per IMP

    Arm title
    		 Methylphenidate First
    Arm description
    		 participants in this arm received the active IMP first before crossing over to placebo
    Arm type
    		 Experimental

    Investigational medicinal product name
    Methylphenidate
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    0.3mg/kg (rounded to nearest 5mg and capped at maximum dose of 25mg/day) twice per day.

    Number of subjects in period 1 [1]
    		Placebo First Methylphenidate First
    Started
    20
    20
    Completed
    20
    20
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: See CSR

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo First
    Reporting group description
    		 participants in this arm received placebo first.

    Reporting group title
    Methylphenidate First
    Reporting group description
    		 participants in this arm received the active IMP first before crossing over to placebo

    Reporting group values
    		 Placebo First Methylphenidate First Total
    Number of subjects
    		 20 20 40
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 20 20 40
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Gender categorical
    Units: Subjects
        Female
    		 4 2 6
        Male
    		 16 18 34
    Subject analysis sets

    Subject analysis set title
    Normal Caudate
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Normal caudate 123I-ioflupane specific binding ratio (N=22) Comparison of IMP group median score vs placebo group median score

    Subject analysis set title
    Low Caudate Group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Low caudate 123I-ioflupane specific binding ratio (N=18) Comparison of IMP group median score vs placebo group median score

    Subject analysis sets values
    		 Normal Caudate Low Caudate Group
    Number of subjects
    22
    18
    Age categorical
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    22
    18
        From 65-84 years
    0
    0
        85 years and over
    0
    0
    Age continuous
    Units:
        
    ±
    ±
    Gender categorical
    Units: Subjects
        Female
    5
    1
        Male
    17
    17

    End points

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    End points reporting groups
    Reporting group title
    Placebo First
    Reporting group description
    		 participants in this arm received placebo first.

    Reporting group title
    Methylphenidate First
    Reporting group description
    		 participants in this arm received the active IMP first before crossing over to placebo

    Subject analysis set title
    Normal Caudate
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Normal caudate 123I-ioflupane specific binding ratio (N=22) Comparison of IMP group median score vs placebo group median score

    Subject analysis set title
    Low Caudate Group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Low caudate 123I-ioflupane specific binding ratio (N=18) Comparison of IMP group median score vs placebo group median score

    Primary: Primary Outcome Measure

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    End point title
    		 Primary Outcome Measure [1]
    End point description
    End point type
    Primary
    End point timeframe
    Assessed by comparing scores at placebo visit to those at active IMP visit.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: See CSR
    End point values
    		 Normal Caudate Low Caudate Group
    Number of subjects analysed
    22
    18
    Units: Milliseconds
    median (inter-quartile range (Q1-Q3))
        Placebo
    357 (325 to 392)
    382 (359 to 429)
        Methylphenidate
    362 (331 to 378)
    369 (347 to 398)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    From consent to the final MRI study visit.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 None
    Dictionary version
    0
    Reporting groups
    Reporting group title
    All participants
    Reporting group description
    		 All participants affected by adverse events (n=24/40).

    Serious adverse events
    		 All participants
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 40 (0.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 All participants
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 40 (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: There were no serious adverse events. One participant discontinued methylphenidate and withdrew from the trial due to unpleasant feelings of restlessness that were considered likely secondary to the treatment. Heart rate was significantly increased on methylphenidate compared to placebo (median change = 5·5 beats per minute; 95% CI [3, 12]; P<0·001). Systolic blood pressure was not different between methylphenidate and placebo (median change = 1·5mmHg; 95% CI [-2·5, 8]; P=0·21).

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Feb 2014
    Protocol amendment 1
    05 Mar 2014
    Protocol amendment 2
    13 Jun 2014
    Protocol amendment 3
    21 Oct 2014
    Protocol amendment 4
    12 Nov 2014
    Protocol amendment 5
    19 Jul 2016
    Protocol amendment 6

    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.
    See the attached CSR for a complete description of the study, results and conclusions.
    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.

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