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

Primary Purpose

Attention Deficit-Hyperactivity Disorder

Status

Completed

Phase

Phase 4

Locations

Norway

Study Type

Interventional

Intervention

Ritalin

Placebo

About this trial

This is an interventional basic science trial for Attention Deficit-Hyperactivity Disorder focused on measuring Decision-Making, functional MRI, pharmacological MRI, Reinforcement Learning, Methylphenidate

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Exclusion Criteria:

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.
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)

Sites / Locations

Department of Psychology, University of Oslo
Adult ADHD diagnostic clinic, Vestre Viken Hospital Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Behavioral

fMRI-arm

Arm Description

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.*

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.*

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT01831622

First Posted

April 9, 2013

Last Updated

December 1, 2015

Sponsor

Mats Fredriksen

Collaborators

The Research Council of Norway, The Hospital of Vestfold, Norwegian Institute of Public Health

1. Study Identification

Unique Protocol Identification Number

NCT01831622

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

June 2013 (undefined)

Primary Completion Date

June 2015 (Actual)

Study Completion Date

June 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mats Fredriksen

Collaborators

The Research Council of Norway, The Hospital of Vestfold, Norwegian Institute of Public Health

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Attention Deficit-Hyperactivity Disorder

Keywords

Decision-Making, functional MRI, pharmacological MRI, Reinforcement Learning, Methylphenidate

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 4

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

131 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Behavioral

Arm Type

Experimental

Arm Description

Arm Title

fMRI-arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ritalin

Other Intervention Name(s)

Methylphenidate, MPH

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Sugar pill

Intervention Description

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

Primary Outcome Measure Information:

Title

Effect of ADHD medication on decision making

Description

Time Frame

by may 2015 (up to 3 years)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

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. Exclusion Criteria: 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. 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mats Fredriksen, MD

Organizational Affiliation

Vestre Viken Hospital Trust and the University of Oslo

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Guido P Biele, PhD

Organizational Affiliation

University of Oslo

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Tor Endestad, PhD

Organizational Affiliation

University of Oslo

Official's Role

Study Chair

Facility Information:

Facility Name

Department of Psychology, University of Oslo

City

Oslo

ZIP/Postal Code

0373

Country

Norway

Facility Name

Adult ADHD diagnostic clinic, Vestre Viken Hospital Trust

City

Tønsberg

ZIP/Postal Code

3103

Country

Norway

12. IPD Sharing Statement

Citations:

PubMed Identifier

28861338

Citation

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.

Results Reference

derived

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

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