Influence of Stimulant Medication on Brain Processes for Decision Making in Attention Deficit Hyperactivity Disorder

NCT ID: NCT01831622

Last Updated: 2015-12-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 131 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2015-06-30

Brief 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. 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.

Conditions

Attention Deficit-Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Behavioral

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.*

Group Type: EXPERIMENTAL

Ritalin

Intervention Type: DRUG

On one of the two test-dates the patient participant is administered methylphenidate, in the dose prescribed by the patients doctor.

Placebo

Intervention Type: DRUG

On one of the test-dates the patient participants are administered a sugar pill, matching their prescribes medical dose.

fMRI-arm

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.*

Group Type: EXPERIMENTAL

Ritalin

Intervention Type: DRUG

On one of the two test-dates the patient participant is administered methylphenidate, in the dose prescribed by the patients doctor.

Placebo

Intervention Type: DRUG

On one of the test-dates the patient participants are administered a sugar pill, matching their prescribes medical dose.

Interventions

Ritalin

On one of the two test-dates the patient participant is administered methylphenidate, in the dose prescribed by the patients doctor.

Intervention Type: DRUG

Placebo

On one of the test-dates the patient participants are administered a sugar pill, matching their prescribes medical dose.

Intervention Type: DRUG

Other Intervention Names

Methylphenidate; MPH; Sugar pill

Eligibility Criteria

Inclusion Criteria

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".

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.

• MRI specific criteria: contraindications for MRI (i.e. metallic or circuit-containing implants, severe claustrophobia)

Exclusion Criteria

• 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.
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The Research Council of Norway

OTHER

Sponsor Role: collaborator

The Hospital of Vestfold

OTHER

Sponsor Role: collaborator

Norwegian Institute of Public Health

OTHER_GOV

Sponsor Role: collaborator

Mats Fredriksen

OTHER

Sponsor Role: lead

Responsible Party

Mats Fredriksen

Researcher MD, PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Mats Fredriksen, MD

Role: PRINCIPAL_INVESTIGATOR

Vestre Viken Hospital Trust and the University of Oslo

Guido P Biele, PhD

Role: STUDY_DIRECTOR

University of Oslo

Tor Endestad, PhD

Role: STUDY_CHAIR

University of Oslo

Locations

Department of Psychology, University of Oslo

Oslo, Oslo County, Norway

Adult ADHD diagnostic clinic, Vestre Viken Hospital Trust

Tønsberg, Tønsberg, Norway

Countries

Norway

References

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.

Reference Type: DERIVED

PMID: 28861338 (View on PubMed)

Other Identifiers

2012-005246-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2012/1105-8

Identifier Type: OTHER

Identifier Source: secondary_id

2011/1585-10

Identifier Type: OTHER

Identifier Source: secondary_id

2012-005246-38

Identifier Type: -

Identifier Source: org_study_id