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   43861   clinical trials with a EudraCT protocol, of which   7284   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:
    Antidepressant controlled trial for negative symptoms in schizophrenia (ACTIONS)

    Summary
    EudraCT number
    		 2009-009235-30
    Trial protocol
    		 GB  
    Global end of trial date
    08 Dec 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Feb 2016
    First version publication date
    13 Feb 2016
    Other versions
    Summary report(s)
    		 ACTIONS final report

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CRO1250
    Additional study identifiers
    ISRCTN number
    		 ISRCTN42305247
    US NCT number
    		 NCT01032083
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Imperial College
    Sponsor organisation address
    Exhibition Road, London, United Kingdom, SW7 2AZ
    Public contact
    Clinical Trials Office, Centre for Mental Health, Imperial College, v.leeson@imperial.ac.uk
    Scientific contact
    Clinical Trials Office, Centre for Mental Health, Imperial College, v.leeson@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
    01 Jul 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    09 Sep 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Dec 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To establish the clinical and cost effectiveness of augmentation of antipsychotic medication with the antidepressant, citalopram, for the management of negative symptoms in schizophrenia.
    Protection of trial subjects
    Thorough monitoring of adverse events and participant wellbeing occurred as part of the assessment process. During assessment and testing, breaks were provided to minimise possible fatigue or stress, and if indicated,the assessments were spread over several days.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Aug 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 62
    Worldwide total number of subjects
    62
    EEA total number of subjects
    62
    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)
    62
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Individuals were identified from multidisciplinary teams in adult psychiatry in the UK, treating people with schizophrenia as either inpatients or outpatients.

    Pre-assignment
    Screening details
    		 Individuals with an established schizophrenic illness characterised by persistent negative symptoms at a criterion level of severity, despite treatment with antipsychotic medication.

    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, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 active (citalopram)
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    citalopram
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    one capsule (20mg) a day for 48 weeks, but at 4 weeks, a participant’s clinician had the option to increase the dose to two capsules (40mg) a day for the remainder of the study.

    Arm title
    		 placebo
    Arm description
    		 -
    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
    one capsule a day for 48 weeks, but at 4 weeks, a participant’s clinician had the option to increase the dose to two capsules a day for the remainder of the study.

    Number of subjects in period 1
    		active (citalopram) placebo
    Started
    30
    32
    Completed
    19
    23
    Not completed
    11
    9
         Consent withdrawn by subject
    11
    9

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    active (citalopram)
    Reporting group description
    		 -

    Reporting group title
    placebo
    Reporting group description
    		 -

    Reporting group values
    		 active (citalopram) placebo Total
    Number of subjects
    		 30 32 62
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 43.02 ± 12.3 45.1 ± 12.3 -
    Gender categorical
    Units: Subjects
        Female
    		 4 10 14
        Male
    		 26 22 48

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    active (citalopram)
    Reporting group description
    		 -

    Reporting group title
    placebo
    Reporting group description
    		 -

    Primary: quality of life

    		 Close Top of page
    End point title
    		 quality of life
    End point description
    End point type
    Primary
    End point timeframe
    12 weeks
    End point values
    		 active (citalopram) placebo
    Number of subjects analysed
    21
    25
    Units: quality of life scale score
        number (not applicable)
    52
    49.5
    Statistical analysis title
    		 Difference in 12 week quality of life score
    Statistical analysis description
    Baseline values for variable were included as covariates in regression models and adjusted according to ANCOVA
    Comparison groups
    active (citalopram) v placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.17
    Method
    		 ANCOVA
    Confidence interval

    Primary: quality of life

    		 Close Top of page
    End point title
    		 quality of life
    End point description
    End point type
    Primary
    End point timeframe
    48 weeks
    End point values
    		 active (citalopram) placebo
    Number of subjects analysed
    17
    20
    Units: quality of life scale score
        number (not applicable)
    63.1
    54.5
    Statistical analysis title
    		 Difference in 48 week quality of life score
    Statistical analysis description
    Baseline values for variable were included as covariates in regression models and adjusted according to ANCOVA
    Comparison groups
    active (citalopram) v placebo
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.98
    Method
    		 ANCOVA
    Confidence interval

    Primary: negative symptoms

    		 Close Top of page
    End point title
    		 negative symptoms
    End point description
    End point type
    Primary
    End point timeframe
    12 weeks
    End point values
    		 active (citalopram) placebo
    Number of subjects analysed
    22
    24
    Units: PANSS negative subscale score
        number (not applicable)
    21.5
    23
    Statistical analysis title
    		 Difference in 12 week negative symptom score
    Statistical analysis description
    Baseline values for variable were included as covariates in regression models and adjusted according to ANCOVA
    Comparison groups
    active (citalopram) v placebo
    Number of subjects included in analysis
    46
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.32
    Method
    		 ANCOVA
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    9th September 2011 to 8th December 2014
    Adverse event reporting additional description
    The Antipsychotic Non-Neurological Side-Effects Rating Scale was enhanced to include additional questions relating to known side-effects of citalopram. The assessment was carried out at each timepoint. Where
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16
    Reporting groups
    Reporting group title
    active (citalopram)
    Reporting group description
    		 -

    Reporting group title
    placebo
    Reporting group description
    		 -

    Serious adverse events
    		 active (citalopram) placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 28 (0.00%)
    0 / 32 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 active (citalopram) placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 28 (39.29%)
    16 / 32 (50.00%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 28 (3.57%)
    5 / 32 (15.63%)
         occurrences all number
    20
    4
    Dizziness
         subjects affected / exposed
    5 / 28 (17.86%)
    2 / 32 (6.25%)
         occurrences all number
    5
    3
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    2 / 28 (7.14%)
    3 / 32 (9.38%)
         occurrences all number
    2
    4
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 28 (3.57%)
    3 / 32 (9.38%)
         occurrences all number
    1
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Nov 2011
    New safety information about citalopram was published by the manufacturer in conjunction with the MHRA in late 2011 with a warning about the risk of QTc prolongation and stating that co-administration of citalopram with medicines that prolong the QT interval (including antipsychotic drugs) was therefore contraindicated. Plasma potassium and magnesium levels were measured at baseline while the ECG QTc interval was measured at baseline, 12, 36 and 48 weeks post study entry for all participants entering the study after the Urgent Safety Measures were implemented.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    18 Nov 2011
    An urgent safety measure agreed with the MHRA on 18th November 2011 was not given approval by the Research Ethics Committee until 15th June 2012. The trial was unable to randomise participants during this time
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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-Thu Apr 25 23:08:28 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA