Attention Deficit-Hyperactivity DisorderPhase 4NCT01831622
Influence of Stimulant Medication on Brain Processes for Decision Making in Attention Deficit Hyperactivity Disorder
A Phase 4 study testing Ritalin in people with Attention Deficit-Hyperactivity Disorder, run by Mats Fredriksen at 2 sites in Norway.
Trial summary
The goal of this trial is to investigate the cognitive- and brain-mechanisms underlying decision making (DM) and learning in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD) as well as the modulation of task-related and task-independent brain activation by methylphenidate. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Attention Deficit-Hyperactivity Disorder
- What is being tested?
- Ritalin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 131 participants
- Where
- 2 sitesNorway
- Study dates
- Jun 2013to Jun 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Drug-Naïve Group
- Comply with Diagnostic and Statistical Manual (DSM) -IV criteria for ADHD.
- No history of medication with Methylphenidate.
- Must be between the age of 18 and 40.
- Signed informed consent and expected cooperation of the patients for the intervention and the test dates must be obtained and documented according to International Conference on Harmonisation (ICH) Good Clinical Practice (GCP), and national/local regulations.
- After stable medication is established, these will be incorporated into the study following the procedures of the "drug group".
Show all 15Show fewer
- Drug group
- Comply with DSM-IV criteria for ADHD.
- On stable treatment with MPH.
- Must be between the age of 18 and 40.
- Signed informed consent and expected cooperation of the patients for the intervention and the test dates must be obtained and documented according to ICH GCP, and national/local regulations.
- Healthy Control Group
- Must be between the age of 18 and 40.
- No current psychiatric diagnosis.
- Signed informed consent and expected cooperation of the patients for the intervention and the test dates must be obtained and documented according to ICH GCP, and national/local regulations.
Who cannot join
- Treatment with the following groups of pharmacological agents will be considered as exclusion criteria for participation:
- Antidepressants (MOA-inhibitors, Tricyclic antidepressants, Selective Serotonin Re-uptake Inhibitors)
- Antipsychotics (both first and second generation)
- Anxiolytics/hypnotics (benzodiazepines, barbiturates)
- Opiates
- History of alcohol or drug abuse.
Show all 14Show fewer
- History of moderate to severe head injury.
- Major psychiatric comorbidity (i.e. psychosis, active suicidal ideation or acute exacerbation of other psychiatric condition in need of immediate treatment).
- Epilepsy
- History of severe memory loss
- Under treatment for metabolic disorders
- Severe primary sensory loss
- Any condition contraindicating treatment with methylphenidate will automatically lead to exclusion, since these patients will not receive methylphenidate from clinician and thus will not meet inclusion criteria (including pregnancy, methylphenidate allergies, incompatible concomitant medication etc.).
- MRI specific criteria: contraindications for MRI (i.e. metallic or circuit-containing implants, severe claustrophobia)
Trial locations and contacts
2 sites in 1 country.
Norway2 sites
Department of Psychology, University of Oslo
Oslo, Oslo, 0373
Adult ADHD diagnostic clinic, Vestre Viken Hospital Trust
Tønsberg, Tønsberg, 3103
About this study
The goal of this trial is to investigate the cognitive- and brain-mechanisms underlying decision making (DM) and learning in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD) as well as the modulation of task-related and task-independent brain activation by methylphenidate. The study aims at using a double-blinded, placebo controlled, cross-over, withdrawal design to study the effects of ADHD and methylphenidate in both a behavioural study investigating cognitive effects on decision making and instrumental learning, and a functional MRI (fMRI) study investigating the effects on brain mechanisms during decision making alone. A secondary objective of the trial is to measure the effect of adult ADHD and methylphenidate on cerebral perfusion. This will be done through applying a novel arterial spin labelling MRI-technique on the participants in the fMRI arm of the study.
Read the detailed description
The immediate scientific goal of this trial is to investigate the cognitive- and brain-mechanisms underlying Decision Making (DM) and instrumental learning in young adults with ADHD as well as the modulation of task-related and task-independent brain activation by MPH. In a more applied perspective, the investigators hope this trial will contribute to the development of tools for improved diagnosis and treatment monitoring of ADHD. Diagnostic tools should be based on the understanding of cognitive and brain mechanisms contributing to the symptom manifestation of ADHD. The study aims at using a double-blinded, placebo controlled cross-over withdrawal design to study the effects of ADHD and MPH in both a behavioural study investigating cognitive effects on DM and instrumental learning, and an fMRI study investigating the effects on brain mechanisms during DM alone. The results of the behavioural DM task from the fMRI experiment will be pooled with the data from the behavioural study to achieve higher statistical power in the analysis of the behavioural data.
A distinctive characteristic of this proposal is to gain insight into differences between ADHD-patients and healthy controls and the effects of methylphenidate (MPH) medication with an approach termed "computational psychiatry" (Maia and Frank, 2011). In this approach, the investigators apply mathematical models of cognition to observed behaviour in order to derive latent decision variables characterizing the DM- and instrumental learning processes. When combined with neuroimaging methods, computational models allow identification of differences in affective and cognitive processes together with the neurobiological processes that underlie these differences (Frank et al., 2004). Such insights should be the foundation of new tools for diagnosis and therapeutic treatment of ADHD.
- Conditions
- Attention Deficit-Hyperactivity Disorder
- Being tested
- Ritalin, Placebo
- Keywords
- Decision-Making, functional MRI, pharmacological MRI, Reinforcement Learning, Methylphenidate
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RitalinDrug
Also called Methylphenidate, MPH
On one of the two test-dates the patient participant is administered methylphenidate, in the dose prescribed by the patients doctor.
PlaceboDrug
Also called Sugar pill
On one of the test-dates the patient participants are administered a sugar pill, matching their prescribes medical dose.
| Study group | Role | What they receive |
|---|---|---|
| Behavioral | Experimental | Cognitive testing of participants. Asterisk applies for patient group.
Day 1:
* Patient arrives having abstained medication for minimum 20 hours.*
* Administer either Ritalin or placebo intervention, and wait 60 minutes before computer-testing.*
* Case Report Form (CRF), ASRS and Wechsler Adult Intelligence Scale (WAIS) subtests.
* Blood sample, if consented.*
* Computerized testing.
* Administer opposite treatment.*
Day 2:
* Patient arrives having abstained medication for a minimum of 20 hours.*
* Administer either Ritalin or placebo intervention (opposite of Day 1), and wait 60 minutes before computer-testing.*
* CRF 3, ASRS and Edinburgh Handedness Inventory (EHI).
* Blood sample, if consented.*
* Computerized testing.
* Administer opposite treatment.* Receives: Drug: Ritalin; Drug: Placebo |
| fMRI-arm | Experimental | Asterisk applies only for patient group.
Day 1:
* Patient arrives having abstained medication for minimum 20 hours.*
* Administer either Ritalin or placebo intervention, and wait 60 minutes before MRI testing.*
* CRF 2, Adult ASRS and WAIS subtests.
* Blood sample, if consented.*
* Computerized testing.
* Administer opposite treatment to ensure the patients have not been withheld from medication for too long while keeping blind.*
Day 2 (after 14 - 40 days):
* Patient arrives having abstained medication for a minimum of 20 hours.*
* Administer either Ritalin or placebo intervention, and wait 60 minutes before testing (opposite of Day 1).*
* CRF 3, ASRS and EHI.
* Blood sample, if consented.*
* Computerized testing.
* Administer opposite treatment.* Receives: Drug: Ritalin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of ADHD medication on decision making
The study will both use standard statistical models on reaction time and accuracy data, but also use Bayesian Statistics and mathematical modelling.
The investigators expect higher Drift Diffusion Model drift rate in the controls and patients on medication, and slower drift rate for participants off medication.
Measured: by may 2015 (up to 3 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2015
- Study completionJun 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit-Hyperactivity DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 131 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mats Fredriksen
- Sponsor type
- University, hospital or other
- Collaborators
- The Research Council of Norway, The Hospital of Vestfold, Norwegian Institute of Public Health
- Responsible party
- Sponsor-investigator, Mats Fredriksen, University of Oslo
- Investigators
- Mats Fredriksen, MD, Principal investigator, Vestre Viken Hospital Trust and the University of OsloGuido P Biele, PhD, Study director, University of OsloTor Endestad, PhD, Study chair, University of Oslo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01831622
- Sponsor's protocol ID
- 2012-005246-38
- Other IDs
- 2012-005246-38, 2012/1105-8, 2011/1585-10
- Status last verified
- Dec 2015
- First submitted
- 9 Apr 2013
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Mowinckel AM, Alnaes D, Pedersen ML, Ziegler S, Fredriksen M, Kaufmann T, Sonuga-Barke E, Endestad T, Westlye LT, Biele G. Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD. Neuroimage Clin. 2017 Mar 30;16:369-382. doi: 10.1016/j.nicl.2017.03.008. eCollection 2017.
PubMed 28861338
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Stimulant Medication on Brain Processes for Decision Making in Attention Deficit Hyperactivity Disorder
- ClinicalTrials.gov ID
- NCT01831622
- Acronym / sponsor ID
- 2012-005246-38
- Conditions
- Attention Deficit-Hyperactivity Disorder
- Keywords
- Decision-Making, functional MRI, pharmacological MRI, Reinforcement Learning, Methylphenidate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 131 participants (actual)
- Lead sponsor
- Mats FredriksenUniversity, hospital or other
- Collaborators
- The Research Council of Norway, The Hospital of Vestfold, Norwegian Institute of Public Health
- Study start
- Jun 2013
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 15 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this trial is to investigate the cognitive- and brain-mechanisms underlying decision making (DM) and learning in young adults with Attention-Deficit/Hyperactivity Disorder (ADHD) as well as the modulation of task-related and task-independent brain activation by methylphenidate. The study aims at using a double-blinded, placebo controlled, cross-over, withdrawal design to study the effects of ADHD and methylphenidate in both a behavioural study investigating cognitive effects on decision making and instrumental learning, and a functional MRI (fMRI) study investigating the effects on brain mechanisms during decision making alone. A secondary objective of the trial is to measure the effect of adult ADHD and methylphenidate on cerebral perfusion. This will be done through applying a novel arterial spin labelling MRI-technique on the participants in the fMRI arm of the study.
Detailed description
The immediate scientific goal of this trial is to investigate the cognitive- and brain-mechanisms underlying Decision Making (DM) and instrumental learning in young adults with ADHD as well as the modulation of task-related and task-independent brain activation by MPH. In a more applied perspective, the investigators hope this trial will contribute to the development of tools for improved diagnosis and treatment monitoring of ADHD. Diagnostic tools should be based on the understanding of cognitive and brain mechanisms contributing to the symptom manifestation of ADHD. The study aims at using a double-blinded, placebo controlled cross-over withdrawal design to study the effects of ADHD and MPH in both a behavioural study investigating cognitive effects on DM and instrumental learning, and an fMRI study investigating the effects on brain mechanisms during DM alone. The results of the behavioural DM task from the fMRI experiment will be pooled with the data from the behavioural study to achieve higher statistical power in the analysis of the behavioural data.
A distinctive characteristic of this proposal is to gain insight into differences between ADHD-patients and healthy controls and the effects of methylphenidate (MPH) medication with an approach termed "computational psychiatry" (Maia and Frank, 2011). In this approach, the investigators apply mathematical models of cognition to observed behaviour in order to derive latent decision variables characterizing the DM- and instrumental learning processes. When combined with neuroimaging methods, computational models allow identification of differences in affective and cognitive processes together with the neurobiological processes that underlie these differences (Frank et al., 2004). Such insights should be the foundation of new tools for diagnosis and therapeutic treatment of ADHD.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Behavioral | Experimental | Drug: Ritalin, Drug: PlaceboCognitive testing of participants. Asterisk applies for patient group. Day 1: * Patient arrives having abstained medication for minimum 20 hours.* * Administer either Ritalin or placebo intervention, and wait 60 minutes before computer-testing.* * Case Report Form (CRF), ASRS and Wechsler Adult Intelligence Scale (WAIS) subtests. * Blood sample, if consented.* * Computerized testing. * Administer opposite treatment.* Day 2: * Patient arrives having abstained medication for a minimum of 20 hours.* * Administer either Ritalin or placebo intervention (opposite of Day 1), and wait 60 minutes before computer-testing.* * CRF 3, ASRS and Edinburgh Handedness Inventory (EHI). * Blood sample, if consented.* * Computerized testing. * Administer opposite treatment.* |
| fMRI-arm | Experimental | Drug: Ritalin, Drug: PlaceboAsterisk applies only for patient group. Day 1: * Patient arrives having abstained medication for minimum 20 hours.* * Administer either Ritalin or placebo intervention, and wait 60 minutes before MRI testing.* * CRF 2, Adult ASRS and WAIS subtests. * Blood sample, if consented.* * Computerized testing. * Administer opposite treatment to ensure the patients have not been withheld from medication for too long while keeping blind.* Day 2 (after 14 - 40 days): * Patient arrives having abstained medication for a minimum of 20 hours.* * Administer either Ritalin or placebo intervention, and wait 60 minutes before testing (opposite of Day 1).* * CRF 3, ASRS and EHI. * Blood sample, if consented.* * Computerized testing. * Administer opposite treatment.* |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Drug-Naïve Group
- Comply with Diagnostic and Statistical Manual (DSM) -IV criteria for ADHD.
- No history of medication with Methylphenidate.
- Must be between the age of 18 and 40.
- Signed informed consent and expected cooperation of the patients for the intervention and the test dates must be obtained and documented according to International Conference on Harmonisation (ICH) Good Clinical Practice (GCP), and national/local regulations.
Key exclusion criteria (14 listed)
- Treatment with the following groups of pharmacological agents will be considered as exclusion criteria for participation:
- Antidepressants (MOA-inhibitors, Tricyclic antidepressants, Selective Serotonin Re-uptake Inhibitors)
- Antipsychotics (both first and second generation)
- Anxiolytics/hypnotics (benzodiazepines, barbiturates)
- Opiates
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RitalinAlso: Methylphenidate, MPHOn one of the two test-dates the patient participant is administered methylphenidate, in the dose prescribed by the patients doctor. | Drug | Behavioral, fMRI-arm |
| PlaceboAlso: Sugar pillOn one of the test-dates the patient participants are administered a sugar pill, matching their prescribes medical dose. | Drug | Behavioral, fMRI-arm |
Primary outcome
Effect of ADHD medication on decision making
Time frame: by may 2015 (up to 3 years)
The study will both use standard statistical models on reaction time and accuracy data, but also use Bayesian Statistics and mathematical modelling. The investigators expect higher Drift Diffusion Model drift rate in the controls and patients on medication, and slower drift rate for participants off medication.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
- Derived from this study: PubMed 28861338Mowinckel AM, Alnaes D, Pedersen ML, Ziegler S, Fredriksen M, Kaufmann T, Sonuga-Barke E, Endestad T, Westlye LT, Biele G. Increased default-mode variability is related to reduced task-performance and is evident in adults with ADHD. Neuroimage Clin. 2017 Mar 30;16:369-382. doi: 10.1016/j.nicl.2017.03.008. eCollection 2017.
Related trials for Attention Deficit-Hyperactivity Disorder
Enrolling by invitationPhase 3
An Open-Label Study to Assess the Long-Term Safety of Solriamfetol in Children and Adolescents With ADHD
ADHD
Not yet recruitingPhase 2
Lisdexamfetamine For the Treatment of Conduct Disorder in Children
Conduct Disorder
RecruitingObservational study
Augmenting Parent Management Training for Child Temper Outbursts Using a Digital Tool
Disruptive Behavior Disorders, Conduct Disorder
Recruiting
Micronutrient Supplementation and Chronotherapy in Children With ADHD
Attention Deficit Hyperactivity Disorder (ADHD)
RecruitingPhase 3
Forward Treatment of Attention Deficit and Hyperactivity Using Solriamfetol (FOCUS-2)
ADHD
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mats Fredriksen, MD principal investigator
Vestre Viken Hospital Trust and the University of Oslo
Guido P Biele, PhD study director
University of Oslo
Tor Endestad, PhD study chair
University of Oslo
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ritalin in people with Attention Deficit-Hyperactivity Disorder, run by Mats Fredriksen at 2 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of ADHD medication on decision making (time frame: by may 2015 (up to 3 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01831622, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2015.