EEG-MRI Imaging of Methylphenidate Effects in Adult ADHD and Attentional Symptoms in Mood Disorders

NCT05832489 | Recruiting Phase 3

• 1 other identifier: 7347
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.To determine the effect of methylphenidate on baseline brain flow in the two clinical populations and in controls (healthy subjects).
2. 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. 3.To confirm the effect of methylphenidate on the maintenance of cortical arousal.
4. 4.To distinguish the brain networks impacted by methylphenidate (maintenance of attention or inhibition) with MRI and EEG.

Conditions

Adult ADHD; Adult-onset ADHD With Mood Disorder

Keywords

Adult ADHD; Sustained attention; fMRI; EEG; Pharmacoimaging; Methylphenidate

Outcome Measures

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.

  2 hours after intake of methylphenidate or placebo

Secondary Outcomes (5)

• Decrease in rCBF (regional Cerebral Blood Flow) in the methylphenidate vs. placebo condition, in the different groups (group x treatment interaction).

  2 hours after intake of methylphenidate or placebo

• Improved cognitive performance in sustained attention and inhibition tasks (SART : number of errors) following methylphenidate administration, in the different groups.

  2 hours after intake of methylphenidate or placebo

• 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

  3 hours after intake of methylphenidate or placebo

• MRI: Interaction group x treatment x task on brain activation related to sustained attention and inhibition corresponding to each of these tasks.

  2 hours after intake of methylphenidate or placebo

• EEG evoked potentials: Interaction group x treatment x task on the amplitude of the P300 wave related to sustained attention (P300b) and related to inhibition (P300a) corresponding to each of these tasks.

  3 hours after intake of methylphenidate or placebo

Study Arms (3)

Group A

EXPERIMENTAL

Adult patients with ADHD (ADHD-P) receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)

Drug: Placebo; Drug: Methylphenidate immediate release 25mg

Group B

EXPERIMENTAL

Adult patients with attention deficit due to/emphasized by mood disorders (ADHD-HD) receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)

Drug: Placebo; Drug: Methylphenidate immediate release 25mg

Group C

EXPERIMENTAL

Adult Healthy controls receive a placebo or 25 mg of methylphenidate 45min before the first and second imaging sessions (MRI+EEG)

Drug: Placebo; Drug: Methylphenidate immediate release 25mg

Interventions

Placebo DRUG

Patients 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.

Also known as: MRI, EEG

Group A; Group B; Group C

Methylphenidate immediate release 25mg DRUG

Patients 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.

Also known as: MRI, EEG

Group A; Group B; Group C

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• For a woman of childbearing age: negative blood pregnancy test and effective contraception throughout the study (intrauterine device, sterilization, estro-progestogen or progestogen per os, injectable or in the form of an implant or ring) and refusal to perform a pregnancy test before each MRI)
• Diagnosis of ADHD according to DSM-5 (in particular criterion B: presence of symptoms before the age of 12 years) NB: the diagnosis was not necessarily made at this age.
• Subject with or without methylphenidate treatment
• Association of ADHD symptoms with attentional disorders according to the combination of the following criteria :
• Diagnosis of Recurrent Depressive Disorder or Bipolar Disorder according to DSM-5
• DSM-5 Adult ADHD Criteria A (at least 5 symptoms of inattention and/or hyperactivity/impulsivity)
• Absence of Criterion D during childhood, adolescence and before mood disorders (i.e., no significant impact with reduced quality of social, academic or occupational functioning)
• Presence of Criterion D at present (symptoms have a significant impact with a reduction in the quality of social, academic or professional functioning)
• Subject with or without approved mood disorder treatment: Mood stabilizers (lithium, valproate, lamotrigine); antidepressants (SSRIs, IRSNa ≤60mg/j of venlafaxine and ≤60mg/j of duloxetine); benzodiazepines in stable doses for more than a month.
• Subject with or without methylphenidate treatment
• \- Subject with no psychiatric or neurological history

You may not qualify if:

• Subjects with contraindication to methylphenidate :
• hypersensitivity to the active substance,
• glaucoma,
• pheochromocytoma,
• treatment with other indirect sympathomimetics or alpha sympathomimetics (oral and/or nasal routes), irreversible MAOIs
• Hyperthyroidism or thyrotoxicosis,
• Pre-existing cardiovascular disorders including severe hypertension, heart failure, occlusive arterial disease, angina pectoris, congenital heart disease with hemodynamic impact, cardiomyopathy, myocardial infarction, arrhythmias and potentially life-threatening ductopathies (disorders caused by ion channel dysfunction),
• Pre-existing cerebrovascular disorders, brain aneurysms, vascular abnormalities including vasculitis or stroke,
• wheat allergy (other than celiac disease)
• Diagnosis or history of severe depression, anorexia nervosa or anorexic disorder, suicidal tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia, psychopathic or borderline personality disorder.
• Diagnosis or history of episodic and severe (type 1) (and poorly controlled) bipolar (affective) disorder.
• Subjectis with contraindication to performing an MRI: presence of non-removable ferromagnetic body, prosthesis, pacemaker, medication delivered by an implanted pump, vascular clip or stent, heart valve or ventricular shunt
• History that may affect brain anatomy or be related to an abnormality (neonatal suffering, neurosurgical operation, comitiality, stroke, head injury with unconsciousness of more than 15 minutes and mental retardation)
• Substance Use Disorder as per DSM-5 criteria (except tobacco)
• Pregnant women or, in women of childbearing age and ability (non-sterile), lack of effective contraception

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

Study Sites (1)

Service de Psychiatrie 2, Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

RECRUITING

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Methylphenidate

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

Study Officials

• Sébastien WEIBEL, MD

  Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sébastien WEIBEL, MD

CONTACT

33388115157; sebastien.weibel@chru-strasbourg.fr

Hélène SOAVELO

CONTACT

33388116559; helene.soavelo@chru-strasbourg.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: April 27, 2023
• Study Start: February 26, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)