A Study of Concerta XL on reducing ADHD symptoms and behavioural problems in adult offenders with ADHD
| ISRCTN | ISRCTN16827947 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16827947 |
| EudraCT/CTIS number | 2015-004271-78 |
| Secondary identifying numbers | CPMS 30391 |
- Submission date
- 18/05/2016
- Registration date
- 31/05/2016
- Last edited
- 20/09/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Mental and Behavioural Disorders
Plain English summary of protocol
Background and study aims
Attention deficit hyperactivity disorder (ADHD) is a common disorder that affects behaviour. ADHD can present in a number of ways, but common symptoms include a short attention span, restlessness, hyperactivity and impulsiveness. These symptoms often overlap with and could be better explained by other common mental health disorders seen in offenders. A particular concern for children with ADHD is the high risk for developing antisocial behaviour during adolescence and young adulthood. Previous studies have shown that around 30% of adolescent and 26% of adult prisoners have ADHD. Currently, the drug methylphenidate is the first line treatment recommended for ADHD with severe impairment in the UK. Despite known effects of methylphenidate on ADHD symptoms, it is uncommon for offender mental health teams to diagnose and treat ADHD. The reason is uncertainty over the effects of methylphenidate on ADHD and behavioural outcomes in offender populations, where ADHD is often accompanied by conduct problems, substance abuse and stress related disorders. The aim of this study is to investigate the effects of methylphenidate in young male prisoners with ADHD.
Who can participate?
Male prisoners aged between 16 and 25 years with ADHD.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group are treated with a placebo (dummy pill) for eight weeks. Those in the second group are treated with methylphenidate for eight weeks. This involves gradually increasing the dose to find the best balance of symptom improvement against side effects for the first five weeks and then maintaining the dose for a further three weeks. At the start of the study and then after eight weeks, participants complete a number of questionnaires in order to find out if their ADHD symptoms, well-being and attitudes towards violence have changed. The prison officers and education staff also complete a questionnaire to find out if the prisoner’s level of aggressive behaviour has changed.
What are the possible benefits and risks of participating?
Study participants may benefit from receiving the diagnosis of ADHD and treatment for the disorder, as all participants will be offered treatment once the 8 week trial is completed. Common side effects from medication such as appetite reduction and sleep disturbance are usually minor and reduce with time, but can lead to some participants withdrawing from treatment. Serious side effects are rarely reported in ADHD treatment trials and so are likely to be rare and unexpected.
Where is the study run from?
The study is run from King’s College London and takes place in two prisons, one in England and one in Scotland (UK)
When is the study starting and how long is it expected to run for?
May 2014 to August 2019
Who is funding the study?
This project is funded by the Efficacy and Mechanism Evaluation (EME) programme, a partnership between the Medical Research Council (MRC) (UK) and the National Institute for Health Research (UK). Janssen-Cilag Ltd. supplied Concerta XL
Who is the main contact?
Professor Philip Asherson
philip.asherson@kcl.ac.uk
Contact information
Scientific
Institute of Psychiatry Psychology and Neuroscience
King’s College London
De Crespigny Park
London
SE5 8AF
United Kingdom
 ORCID ID |
0000-0003-2667-2254 |
|---|---|
| Phone | +44 20 7848 0078 |
| philip.asherson@kcl.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Screening, Diagnosis, Process of Care, Drug, Psychological & Behavioural |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Randomised controlled trial of the short term effects of OROS-methylphenidate on ADHD symptoms and behavioural outcomes in young male prisoners with attention deficit hyperactivity disorder |
| Study acronym | CIAO-II |
| Study objectives | Current study hypothesis as of 22/01/2021: The overall aim of the trial is to investigate the effects of Methylphenidate extended release (OROS MPH) in young male prisoners (age 16-25) meeting DSM-5 diagnostic criteria for ADHD. Hypotheses: 1. OROS-MPH is better than placebo in reducing inattention and hyperactivity-impulsivity in young male prisoners meeting diagnostic criteria for DSM-5 ADHD 2. OROS-MPH is better than placebo at reducing secondary outcomes that are key indicators of behavioural and functional impairments used in the management of young prisoners in the UK (including emotional dysregulation, antisocial behaviour in the prison, violent attitudes) 3. Improvements in secondary behavioural outcomes due to OROS-methylphenidate are mediated by improvements in ADHD symptoms or emotional dysregulation Previous study hypothesis: The overall aim of the trial is investigate the effects of Methylphenidate extended release (OROS MPH) in young male prisoners (age 16-25) meeting DSM-5 diagnostic criteria for ADHD. Hypotheses: 1. OROS-MPH is better than placebo in reducing inattention and hyperactivity-impulsivity in young male prisoners meeting diagnostic criteria for DSM-5 ADHD 2. OROS-MPH is better than placebo at reducing secondary outcomes that are key indicators of behavioural and functional impairments used in the management of young prisoners in the UK (including emotional dysregulation, antisocial behaviour in the prison, violent attitudesand the number of recorded positive Incentives and Earned Privileges) 3. Improvements in secondary behavioural outcomes due to OROS-methylphenidate are mediated by improvements in ADHD symptoms or emotional dysregulation |
| Ethics approval(s) | Approved 31/05/2016, East of England – Essex Research Ethics Committee, ref: 16/EE/0117 |
| Health condition(s) or problem(s) studied | Current condition as of 22/01/2021: Specialty: Mental Health, Primary sub-specialty: Learning disorders; UKCRC code/ Disease: Mental Health/ Behavioural and emotional disorders with onset usually occurring in childhood and adolescence, ADHD Previous condition: Specialty: Mental Health, Primary sub-specialty: Learning disorders; UKCRC code/ Disease: Mental Health/ Behavioural and emotional disorders with onset usually occurring in childhood and adolescence |
| Intervention | Current interventions as of 22/01/2021: Participants will be randomised to receive 8-weeks treatment with either OROS-MPH or placebo, titrated over 5 weeks to balance ADHD symptom improvement against side effects and then maintained for a further 3 weeks. 200 participants will be recruited with 1:1 ratio of drug to placebo. Randomisation will be conducted by the King’s CTU with blinding of both investigators and participants. Randomisation will take place once informed and signed consent has been obtained, eligibility checks have been completed and before the treatment is started. We will use the King's Clinical Trials Unit’s Independent Randomisation Service, ensuring reliability and credibility in the randomisation process. Random block sizes will be used to control the numbers of subjects allocated to each group, stratified by site and in a 1:1 drug-placebo ratio. Patient characteristics will not be taken into account in the randomisation process, but we expect a balanced ratio of cognitive ability, ADHD symptom severity and co-occurring psychosocial and mental health problems across the drug treatment and placebo groups. Both active medication (Concerta XL 18 mg tablets) and matched placebo will be titrated weekly for 5 weeks and then kept at stable maintenance dose for 3 weeks. The maximum titrated dose (or matching placebo) is as follows: Week 1 = 18 mg (1 tablet); Week 2 = 36 mg (2 tablets); Week 3 = 54 mg (3 tablets); Week 4 = 72 mg (4 tablets); Week 5 = 72 mg (4 tablets); Week 6 = 72 mg (4 tablets); Week 7 = 72mg (4 tablets); Week 8 = 72mg (4 tablets). Titration of dose is conducted by the study psychiatrist. Both the trial investigators and participants are blinded. The titration protocol is followed in the same way for both active medication (IMP) and placebo. Treatment will start at an initial dose of 18 mg (1 tablet) for 1 week, and be increased weekly in 18 mg increments to a maximum of 72 mg (4 tablets) (i.e. 18 mg (1 tablet), 36 mg (2 tablets), 54 mg (3 tablets) and 72 mg (4 tablets). Medication will be reduced by 18 mg (1 tablet) if there is a limiting adverse event, in which case there will be no further increase in medication for the duration of the trial. Medication may be provided either once or twice daily up to the maximum daily dose. Titration upwards will be stopped if all 18 ADHD symptoms are scored as negligible (score of 0 or 1 on the CAARS-O) or absent. Unacceptable levels of adverse effects on the lowest dose of 18mg might lead to a cessation of treatment in a few cases; if this occurs we will ask participants to remain in the trial for the remaining trial assessments. Participants in both groups are followed up at eight weeks. Previous interventions: Participants will be randomised to receive 8-weeks treatment with either OROS-MPH or placebo, titrated over 5 weeks to balance ADHD symptom improvement against side effects and then maintained for a further 3 weeks. 200 participants will be recruited with 1:1 ratio of drug to placebo. Randomisation will be conducted by the King’s CTU with blinding of both investigators and participants. Randomisation will take place once informed and signed consent has been obtained, eligibility checks have been completed and before the treatment is started. We will use the King's Clinical Trials Unit’s Independent Randomisation Service, ensuring reliability and credibility in the randomisation process. Random block sizes will be used to control the numbers of subjects allocated to each group, stratified by site and in a 1:1 drug-placebo ratio. Patient characteristics will not be taken into account in the randomisation process, but we expect a balanced ratio of cognitive ability, ADHD symptom severity and co-occurring psychosocial and mental health problems across the drug treatment and placebo groups. Both active medication (Concerta XL 18 mg tablets) and matched placebo will be titrated weekly for 5 weeks and then kept at stable maintenance dose for 3 weeks. The maximum titrated dose (or matching placebo) is as follows: Week 1 = 18 mg (1 tablet); Week 2 = 36 mg (2 tablets); Week 3 = 54 mg (3 tablets); Week 4 = 72 mg (4 tablets); Week 5 = 72 mg (4 tablets); Week 6 = 72 mg (4 tablets); Week 7 = 72mg (4 tablets); Week 8 = 72mg (4 tablets). Titration of dose is conducted by the study psychiatrist. Both the trial investigators and participants are blinded. The titration protocol is followed in the same way for both active medication (IMP) and placebo. Treatment will start at an initial dose of 18 mg (1 tablet) for 1 week, and be increased weekly in 18 mg increments to a maximum of 72 mg (4 tablets) (i.e. 18 mg (1 tablet), 36 mg (2 tablets), 54 mg (3 tablets) and 72 mg (4 tablets). Medication will be reduced by 18 mg (1 tablet) if there is a limiting adverse event, in which case there will be no further increase in medication for the duration of the trial. Medication may be provided either once or twice daily up to the maximum daily dose. Titration upwards will be stopped if all 18 ADHD symptoms are scored as negligible (score of 0 or 1 on the CAARS) or absent. Unacceptable levels of adverse effects on the lowest dose of 18mg might lead to a cessation of treatment in a few cases; if this occurs we will ask participants to remain in the trial for the remaining trial assessments. Participants in both groups are followed up at eight weeks. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | methylphenidate (Concerta XL) |
| Primary outcome measure | Current primary outcome measure as of 22/01/2021: Level of ADHD symptoms measured on the investigator rated Connors Adult ADHD rating scale (CAARS-O) measured at baseline and after 8-weeks of treatment. Previous primary outcome measure: Level of ADHD symptoms measured on the investigator rated Connors Adult ADHD rating scale measured at baseline and after 8-weeks of treatment. |
| Secondary outcome measures | Current secondary outcome measures as of 22/01/2021: 1. Emotional dysregulation rated by the investigator and measured using the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) at baseline, 5, and 8 weeks 2. Critical incidents (adjudications) measured from prison records during the 8-week period before randomisation to the 8-week assessment 3. Aggressive behaviour rated by prison officer and education staff using the Modified Overt Aggression Scale (MOAS) at baseline and 8 weeks 4. Behaviour measured using behaviour report cards from prison staff (BRC-P) and education staff (BRC-E) at baseline and at week 8 5. Engagement in education, occupational, and rehabilitation programs measured from prison records during the 8-week period before randomisation to the 8-week assessment 6. Attitudes towards violence self-rated using the Maudsley Violence Questionnaire (MVQ) at baseline, week 5 and 8 7. Subjective well-being measured using the CORE Outcome Measure (CORE-M) at baseline and 8 weeks 8. Spontaneous mind wandering self-rated using the mind excessively wandering scale (MEWS) at baseline, 5, and 8 weeks 9. General psychopathology measured using the Brief Symptoms Inventory (BSI) at baseline, 5, and 8 weeks 10. Symptoms of irritability measured using the Affective Reactivity Index - Self Report (ARI-S) at baseline, 5, and 8 weeks 11. Overall health measured using Clinical Global Impression (CGI) at baseline, 5, and 8 weeks Previous secondary outcome measures: 1. Emotional dysregulation is rated by the investigator and measured on the Wender-Reimherr Adult ADHD Diagnostic Scale at baseline and 8 weeks 2. Number of negative Incentives and Earned Privileges (IEPs) and adjudications for antisocial behaviour and rule breaking reported in the prison records at baseline and 8 weeks 3. Aggressive behaviour is rated by prison officer and education staff using the Modified Overt Aggression Scale at baseline and 8 weeks 4. Number of positive incentive and earned privileges (IEPs) for positive engagement in education, occupational and rehabilitation programs recorded in the prison records at baseline and 8 weeks 5. Attitudes towards violence are self-rated using the Maudsley Violence Questionnaire at baseline and 8 weeks 6. Subjective well-being is measured using the CORE Outcome Measure (CORE_OM) at baseline and 8 weeks |
| Overall study start date | 21/05/2014 |
| Completion date | 27/08/2019 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Upper age limit | 25 Years |
| Sex | Male |
| Target number of participants | Planned Sample Size: 200; UK Sample Size: 200 |
| Key inclusion criteria | Current participant inclusion criteria as of 22/01/2021: 1. Male, aged between 16 and 25 years 2. English speaking 3. Able to provide informed consent (understand the information sheet and make an informed decision taking into account pros and cons of study participation) 4. Meet clinical diagnostic criteria for DSM-5 ADHD: 5 or more current symptoms of ADHD in either the inattentive or hyperactive-impulsive symptom domains; 6 or more symptoms of ADHD in either the inattentive or hyperactive/impulsive symptom domains before the age of 12 years; Where it is not possible to gain sufficient clinical information to score childhood symptoms of ADHD, the operational criteria will be adapted to include evidence of several ADHD symptoms with impairment starting before the age of 12 years, and 5 or more symptoms currently with moderate to severe impairment 5. Persistent trait like (non-episodic) course of symptoms 6. Impairments in two or more clinical or psychosocial domains and two or more settings from symptoms of ADHD 7. Onset of symptoms before the age of 12 years Previous participant inclusion criteria: 1. Male, aged between 16 and 25 years 2. English speaking 3. Able to provide informed consent (understand the information sheet and make an informed decision taking into account pros and cons of study participation) 4. Meet clinical diagnostic criteria for DSM-5 ADHD: 5 or more current symptoms of ADHD in either the inattentive or hyperactive-impulsive symptom domains; 6 or more symptoms of ADHD in either the inattentive or hyperactiveimpulsive symptom domains before the age of 12 years; Where it is not possible to gain sufficient clinical information to score childhood symptoms of ADHD, the operational criteria will be adapted to include evidence of several ADHD symptoms with impairment starting before the age of 12 years, and 5 or more symptoms currently with moderate to severe impairment 5. Persistent trait like (non-episodic) course of symptoms 6. Impairments in two or more clinical or psychosocial domains and two or more settings from symptoms of ADHD 7. Onset of symptoms before the age of 12 years |
| Key exclusion criteria | Current participant exclusion criteria as of 22/01/2021: 1. Lack of capacity to give informed consent 2. Moderate or severe learning disability, defined as an IQ <60 3. Serious risk of violence to the researcher 4. Current major depression, psychosis, mania or hypomania 5. Past history of bipolar disorder or schizophrenia (such as those with a clear history of episodic mania/hypomania or psychosis unrelated to acute drug intoxication. Excluding chronic emotional dysregulation such as irritability, frustration, anger or emotional-mood instability) 6. Medical contraindications to the use of stimulants (e.g. glaucoma, hypertension, cardiovascular disease or structural heart problem) 7. Drug-seeking behaviour or craving (defined as drug-seeking behaviour that is unusually severe and likely to affect the titration protocol due to unusual and excessive demands for drugs; or where there is a current withdrawal syndrome from an addition disorder with drug dependency) 8. Taking contraindicated medication (e.g. Clonidine, Courmarins, Monoamine oxibase inhibitors, Moclobemide, Rasagline) during the four weeks prior to randomisation 9. Receiving any ADHD medication between consent for screening and randomisation Previous participant exclusion criteria: 1. Lack capacity to give informed consent 2. Moderate or severe learning disability, defined as IQ<60 3. Serious risk of violence to the researcher 4. Current major depression, psychosis, mania or hypomania 5. Past history of bipolar disorder or schizophrenia 6. Medical contraindications to the use of stimulants (e.g. glaucoma, hypertension, cardiovascular disease or structural heart problem) 7. Drug seeking behaviour or craving |
| Date of first enrolment | 17/10/2016 |
| Date of final enrolment | 02/04/2019 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
Study participating centres
London
SE28 0NZ
United Kingdom
Falkirk
FK2 0AB
United Kingdom
Sponsor information
Hospital/treatment centre
King’s Health Partners Academic Health Science Centre
Guy’s Hospital
London
SE1 9RT
England
United Kingdom
"ROR" |
https://ror.org/0220mzb33 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/06/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 1. Publication in the NIHR Journals Library for the EME program 2. Publication in prominent peer reviewed journals (e.g. Lancet, British Medical Journal, British Journal of Psychiatry 3. Press release 4. Reporting at national and international psychiatry and offender mental health meetings (e.g. RCPsych annual meeting, European Psychiatry Association, American Association of Child and Adolescent Psychiatry) 5. Reporting at regional training meetings for offender mental health teams 6. Reporting at prominent criminal justice meetings (e.g. Stockholm Criminology Symposium) 7. Workshops/regional meetings with police, probation and offender management teams 8. Dissemination to guideline development groups 9. Information leaflets for service users and presentation at user group meetings (e.g. the annual ADDISS conference) 10. Development of clinical training programs for ADHD in offender mental health 11. Meetings with local commissioning groups (e.g. commissioners for London Offender Mental Health) and service planners in Scotland (e.g. via the Forensic Mental Health Management Care Network) 12. Meetings with offender mental health care teams in prisons and community settings 13. Meetings with offender management units, probation and prison monitoring committees 14. Feedback to participants in Polmont and Isis informing them of the study outcomes and providing information on support for people with ADHD |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 02/12/2019 | 04/12/2019 | Yes | No |
| Basic results | 24/09/2020 | 16/06/2022 | No | No | |
| HRA research summary | 20/09/2023 | No | No |
Editorial Notes
20/09/2023: A link to the HRA research summary was added.
16/06/2022: EU Clinical Trials Register results added.
07/12/2021: The intention to publish date was changed from 01/06/2021 to 01/06/2022.
22/01/2021: The following changes have been made:
1. The acronym has been added.
2. The study hypothesis has been updated.
3. The trial setting has been changed from "Not Specified" to "Other".
4. The overall trial end date has been changed from 12/07/2019 to 27/08/2019.
5. The condition has been updated.
6. The interventions have been updated.
7. The intervention type has been changed from "Other" to "Drug".
8. The primary outcome measure has been updated.
9. The secondary outcome measures have been updated.
10. The participant inclusion criteria have been updated.
11. The participant exclusion criteria have been updated.
12. The recruitment start date has been changed from 12/09/2016 to 17/10/2016.
13. The recruitment end date has been changed from 12/03/2019 to 02/04/2019.
14. The trial participating centres "King’s College London" and "HMP Rochester" have been removed.
15. The trial participating centre "HMP and YOI ISIS" has been changed to "HMP YOI Isis" and the trial participating centre "YOI Polmont" has been changed to "HM YOI Polmont".
16. The plain English summary has been updated accordingly.
17. The intention to publish date has been changed from 14/07/2020 to 01/06/2021.
06/03/2020: The intention to publish date was changed from 30/09/2019 to 14/07/2020.
04/12/2019: Publication reference and EudraCT number added.
16/06/2016: Verified study status with principal investigator, ethics approval information added.
