EEG-MRI Imaging of Methylphenidate Effects in Adult ADHD and Attentional Symptoms in Mood Disorders
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-60
SponsorUniversity Hospital, Strasbourg, France
About this trial
Attention Deficit Hyperactivity Disorder (ADHD) in adults is a common psychiatric disorder, with important consequences in terms of quality of life, mental health (associated disorders and poorer response to treatment), family life, risk of accidents; with a consequent cost for society.
Adult ADHD is frequently associated with psychiatric co-morbidities, and notably associated with mood disorders (major depressive disorder or bipolar disorder) in about 50% of cases.
The diagnosis of ADHD in adults is made in patients with an attentional complaint (pure ADHD or ADHD-P), but also very often in the management of a comorbid mood disorder (ADHD associated with mood disorder, or ADHD-MD). In this case, the ADHD had no impact during childhood and adolescence.
Medication management is well established for ADHD-P, and medication is based on methylphenidate, which has a rapid and significant effect on attentional symptoms and impulsivity. However, in the case of ADHD-HD, there is little evidence of treatment efficacy and the mechanisms of action of methylphenidate at the brain level are poorly understood.
The aim of the study is to determine the neural mechanisms of the effect of methylphenidate, using functional MRI and EEG, in ADHD-P and ADHD-HD patients, and to compare them to healthy subjects. A single dose allows us to observe effects that are then persistent with repeated doses. The aim is to determine, by means of a biomarker, whether methylphenidate treatment responds to the same mechanisms in the different groups and would be relevant in ADHD-P as in ADHD-HD.
Main objective:
To determine whether methylphenidate impacts differently on brain circuits associated with cognitive functions in the two clinical populations studied (adult ADHD patients and patients with post mood disorder attentional deficit) and in comparison to controls.
Secondary objectives:
1. To determine the effect of methylphenidate on baseline brain flow in the two clinical populations and in controls (healthy subjects). 2. To determine whether methylphenidate has a different impact on cognitive performance in the two clinical populations studied and in comparison to controls (healthy subjects). 3. To confirm the effect of methylphenidate on the maintenance of cortical arousal. 4. To distinguish the brain networks impacted by methylphenidate (maintenance of attention or inhibition) with MRI and EEG.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Subject (male or female) aged 18 to 60 years old
Subject affiliated to a social protection health insurance scheme
Subject capable of understanding the objectives and risks of the research and of providing dated and signed informed consent
Subject having been informed of the results of the prior medical examination
Disqualifiers
hypersensitivity to the active substance,
glaucoma,
pheochromocytoma,
treatment with other indirect sympathomimetics or alpha sympathomimetics (oral and/or nasal routes), irreversible MAOIs
Trial design
Design model
Crossover
Treatments tested in this trial
Placebo
DrugPatients will have 2 imaging sessions (MRI and EEG) after either: * methylphenidate immediate release 25 mg * placebo in a cross-over design. The two imaging sessions will be separated by 11 to 87 days.
Methylphenidate immediate release 25mg
DrugPatients will have 2 imaging sessions (MRI and EEG) after either: * methylphenidate immediate release 25 mg * placebo in a cross-over design. The two imaging sessions will be separated by 11 to 87 days.
Treatment groups
80 Participants
are divided into 3 treatment groupsGroup A: Group AExperimental treatment 2 interventions
Group B: Group BExperimental treatment 2 interventions
Group C: Group CExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Effect of methylphenidate on the task vs. rest activation differential (treatment x group interaction) in a region defined by its involvement in the cognitive task and its responsiveness to methylphenidate.
Changes in brain activations from J3-J600 to J14-J90 (MRI) in ADHD patients (ADHD-P and ADHD-HD), compared to healthy subjects(ADHD-P and ADHD-HD), compared to healthy subjects\] ROI (Region of Interest) analysis to maximize power.
Time frame
2 hours after intake of methylphenidate or placeboSecondary outcomes
1
Decrease in rCBF (regional Cerebral Blood Flow) in the methylphenidate vs. placebo condition, in the different groups (group x treatment interaction).
Time frame
2 hours after intake of methylphenidate or placebo2
Improved cognitive performance in sustained attention and inhibition tasks (SART : number of errors) following methylphenidate administration, in the different groups.
Time frame
2 hours after intake of methylphenidate or placebo3
EEG spectrum power in the low frequencies (proportion of delta power (1-4Hz) and theta power EEG bands (4-8Hz)) in the methylphenidate vs. placebo condition
Time frame
3 hours after intake of methylphenidate or placebo4
MRI: Interaction group x treatment x task on brain activation related to sustained attention and inhibition corresponding to each of these tasks.
Time frame
2 hours after intake of methylphenidate or placeboSponsors and contacts
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Source ClinicalTrials.gov