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   43876   clinical trials with a EudraCT protocol, of which   7294   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:
    Looking into the eye of ADHD. Investigating the relationship between ADHD, the delayed circadian rhythm and the functioning of the eye.

    Summary
    EudraCT number
    		 2013-005017-12
    Trial protocol
    		 NL  
    Global end of trial date
    10 May 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Jun 2022
    First version publication date
    12 Jun 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EyeADHD03
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Nederlands Trail Register: NL4187 / NTR4337
    Sponsors
    Sponsor organisation name
    Parnassia Group
    Sponsor organisation address
    Monsterseweg 93, Den Haag, Netherlands, 2553 RJ
    Public contact
    MN Böhmer, Parnassia Groep / PsyQ Haaglanden, +31 0883570126, m.bohmer@parnassiagroep.nl
    Scientific contact
    MN Böhmer, Parnassia Groep / PsyQ Haaglanden, +31 0883570126, m.bohmer@parnassiagroep.nl
    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 Mar 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 May 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    10 May 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The aim of this project is to investigate associations between visual system functioning, ADHD, and the circadian rhythm. We will also investigate the effects on the functioning of the visual system of commonly used treatments for ADHD and related disorders: methylphenidate, light therapy, and melatonin. In case we find visual system deficiencies that are specific to ADHD, the development of an objective diagnostic test for ADHD will come closer. List of objectives: - To determine the prevalence and type of visual system deficiencies in adults with ADHD and in healthy controls. - To study the relationship between visual system deficiencies, ADHD symptoms, circadian rhythm, and comorbid psychiatric disorders. - To evaluate the single-dose effect of methylphenidate, melatonin and bright light on the visual system functioning in adults with ADHD. - To evaluate the effect of a 3-week treatment with these agents on the visual system functioning in adults with ADHD.
    Protection of trial subjects
    In accordance to section 10, subsection 1, of the WMO, the investigator will inform the subjects and the reviewing accredited METC if anything occurs, on the basis of which it appears that the disadvantages of participation may be significantly greater than was foreseen in the research proposal. The study will be suspended pending further review by the accredited METC, except insofar as suspension would jeopardise the subjects’ health. The investigator will take care that all subjects are kept informed.
    Background therapy
    		 (i) Methylphenidate (Mph): In Phase 2: a three-week intervention period of 3 x 20 mg/day of Ritalin ® at 8 AM, 12 PM and 4 PM. Ritalin ® is registered as medicinal treatment for ADHD in children. For adults with ADHD, Mph is widely used internationally and is the first choice of treatment. Mph is a mild CNS stimulant with more prominent effects on mental than on motor activities. Its mode of action in man is not fully understood but its effects are thought to be due to an inhibition of dopamine reuptake in the striatum, without triggering the release of dopamine. In a meta-analysis by Castells et al. (2012), the treatment discontinuation of methylphenidate was studied in 2,496 adult patients from 12 studies. The authors conclude that treatment was more discontinuated in methylphenidate than in placebo due to adverse events. Methylphenidate was more effective for the reduction of ADHD symptoms than placebo. (ii) Light Therapy (LT): In Phase 2: a three-week intervention period of 30 minutes/day of LT in the morning between 7 and 10 AM. LT is effective in the treatment of seasonal affective disorder (Golden et al., 2005; Martensson, Pettersson, Berglund, & Ekselius, 2015) and to phase-shift the sleep-wake cycle (Danielsson, Jansson-Frojmark, Broman, & Markstrom, 2016; Gradisar et al., 2011) The phase shift hypothesis states that a delayed circadian pacemaker plays an important role in SAD, and that morning LT decreases SAD symptoms by generating a phase advance (Lewy, 2009). However, the anti-depressant effect of LT in SAD is not necessarily related to a phase advance of the circadian rhythm (Burgess, Fogg, Young, & Eastman, 2004; Knapen, Gordijn, & Meesters, 2016), whereas the decrease in ADHD severity was (Rybak, McNeely, Mackenzie, Jain, & Levitan, 2006).
    Evidence for comparator
    		 Comparator In Phase 2, a placebo will be used as a comparator for Methylphenidate. For the Light Therapy intervention, no comparator will be used but a waiting list.
    Actual start date of recruitment
    01 Feb 2015
    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
    Netherlands: 95
    Worldwide total number of subjects
    95
    EEA total number of subjects
    95
    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)
    95
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Patients will be recruited consecutively after standard diagnostic assessment from our outpatient adult ADHD clinic at PsyQ from the Hague. The age- and sex-matched healthy controls will be recruited via the patients using the ‘snowball’ sampling method, or if not available, via our own personal network.

    Pre-assignment
    Screening details
    		 Inclusion criteria Participants in Phase 1: ADHD patients and age- (+/- 5 years) and sex-matched healthy controls will participate. All participants will be aged between 18 to 40 years. Participants Phase 2: ADHD patients with refractive errors and/or oversensitivity to light. All participants will be aged between 18 to 40 years.

    Period 1
    Period 1 title
    Phase 1 - Baseline (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    no blinding was applicable

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 ADHD
    Arm description
    		 ADHD patients
    Arm type
    		 Experimental

    Investigational medicinal product name
    Methylphenidate, immediate-release
    Investigational medicinal product code
    Other name
    Ritalin
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Ritalin will be administered as 3 x 20 mg daily, at 8 AM, 12 PM and 4 PM, thus a total daily dosage of 60 mg.

    Investigational medicinal product name
    Placebo-MPH
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo-MPH will be administered as 3 x 1 tablet daily, at 8 AM, 12 PM and 4 PM.

    Investigational medicinal product name
    Light Therapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Lozenge
    Routes of administration
    Unknown use
    Dosage and administration details
    The LT group used the Philips Energy Lightbox® Type HF3308/01 at home, which produces light with an intensity of 10,000 lux at 20 cm distance of the eyes from the light source. Participants were instructed to use the Lightbox at 20 cm from the eyes without glasses or contact lenses, every morning between 7:00h and 9:00h for 30 minutes. The first LT session was in the presence of the researcher to instruct the participants how to correctly administer LT. The LT group filled in a log with their start and end times of every LT session. Participants received daily text messages 10 minutes before the latest possible start time as a reminder for a light therapy session. During weekly telephone appointments with the researchers, compliance was encouraged, the instructions for LT were repeated, and side-effects were evaluated. Due to obligatory COVID-19 restrictions from the Dutch government in 2020, the T2 test days for 2 participants in the light therapy group had to be delayed for a week. T

    Arm title
    		 Controls
    Arm description
    		 Sex and Age-matched Controls
    Arm type
    		 controls

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    		ADHD Controls
    Started
    51
    44
    Baseline measurement
    51
    44
    Completed
    30
    44
    Not completed
    21
    0
         not eligible for treatment
    21
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    ADHD
    Reporting group description
    		 ADHD patients

    Reporting group title
    Controls
    Reporting group description
    		 Sex and Age-matched Controls

    Reporting group values
    		 ADHD Controls Total
    Number of subjects
    		 51 44 95
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Age
    Units: years
        arithmetic mean (standard deviation)
    		 26.51 ± 5.00 27.50 ± 5.67 -
    Gender categorical
    Units: Subjects
        Female
    		 30 25 55
        Male
    		 21 19 40
    ADHD-RS adulthood
    total score on ADHD-RS adulthood
    Units: points
        arithmetic mean (standard deviation)
    		 32.98 ± 7.24 8.93 ± 5.53 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    ADHD
    Reporting group description
    		 ADHD patients

    Reporting group title
    Controls
    Reporting group description
    		 Sex and Age-matched Controls

    Subject analysis set title
    ADHDplac
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The effect of treatment (PLAC vs MEP vs LT) in ADHD

    Subject analysis set title
    ADHDlt
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    ADHD patients who received LT

    Subject analysis set title
    ADHDmph
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    ADHD patients who received methylphenidate

    Primary: Pipr

    		 Close Top of page
    End point title
    		 Pipr
    End point description
    End point type
    Primary
    End point timeframe
    Pipr at T0 for ADHD-controls and Pips at T1 after 3 weeks of treatment in ADHD patients
    End point values
    		 ADHD Controls ADHDplac ADHDlt ADHDmph
    Number of subjects analysed
    51
    44
    10 [1]
    10
    10
    Units: mm
        arithmetic mean (standard deviation)
    1.99 ± .88
    2.20 ± 1.08
    2.6 ± .97
    1.66 ± .54
    2.23 ± 1.11
    Notes
    [1] - ADHD_plac
    Statistical analysis title
    		 Comparison ADHD-controls analysis
    Statistical analysis description
    Independent t-tests and ANOVAs were used explore any differences in general characteristics between ADHD patients and controls.
    Comparison groups
    ADHD v Controls
    Number of subjects included in analysis
    95
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 ≤ 0.05
    Method
    		 t-test, 2-sided
    Confidence interval
    Statistical analysis title
    		 ADHD comparison treatment
    Statistical analysis description
    For Phase 2, ANOVAs were used explore any differences in general characteristics and ADHD-RS between the three interventions (light therapy, methylphenidate and placebo), and compared between T0 and T2. The effects of the three interventions on PIPS outcomes at T2 were compared using linear mixed models with corrected for baseline T0 values of the PIPR outcomes,
    Comparison groups
    ADHDplac v ADHDlt v ADHDmph
    Number of subjects included in analysis
    30
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 ≤ 0.05
    Method
    		 Mixed models analysis
    Confidence interval
    Variability estimate
    Standard deviation

    Adverse events

    		 Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    The sponsor will report the SAEs through the web portal ToetsingOnline to the accredited METC that approved the protocol, within 15 days after the sponsor has first knowledge of the serious adverse events.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 WMO
    Dictionary version
    10.1
    Frequency threshold for reporting non-serious adverse events: 5%
    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 adverse events occured during this study

    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? Yes
    Date
    Interruption
    Restart date
    13 Mar 2020
    Global covid-pandemic
    13 Aug 2020

    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-Sun May 12 14:08:09 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA