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

NCT01831622 | Completed Phase 4 DMC

• 3 other identifiers: 2012-005246-382012/1105-82011/1585-10
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 2

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.

Conditions

Attention Deficit-Hyperactivity Disorder

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  by may 2015 (up to 3 years)

Study Arms (2)

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.\*

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.\*

Drug: Ritalin; Drug: Placebo

Interventions

Ritalin DRUG

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

Also known as: Methylphenidate, MPH

Behavioral; fMRI-arm

Placebo DRUG

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

Also known as: Sugar pill

Behavioral; fMRI-arm

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Mats Fredriksen: lead
• The Research Council of Norway: collaborator
• The Hospital of Vestfold: collaborator
• Norwegian Institute of Public Health: collaborator

Study Sites (2)

Department of Psychology, University of Oslo

Oslo, Oslo County, 0373, Norway

Location

Adult ADHD diagnostic clinic, Vestre Viken Hospital Trust

Tønsberg, Tønsberg, 3103, Norway

Location

Related Publications (1)

• 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.

  PMID: 28861338 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate; 5,10-dihydro-5-methylphenazine; Sugars

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbohydrates

Study Officials

• Mats Fredriksen, MD

  Vestre Viken Hospital Trust and the University of Oslo

  PRINCIPAL INVESTIGATOR

• Guido P Biele, PhD

  University of Oslo

  STUDY DIRECTOR

• Tor Endestad, PhD

  University of Oslo

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Researcher MD, PhD

Study Record Dates

• First Submitted: April 9, 2013
• First Posted: April 15, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: December 2, 2015

Record last verified: 2015-12

Locations

NO (2)