Methylphenidate hydrochloride for Attention deficit hyperactivity disorder (ADHD)

Inclusion criteria

• {"criterion_text":"Common criteria for all groups: - Subject (male or female) aged 18 to 60 years - Subject affiliated to a social health insurance plan, or beneficiary / beneficiary of such a plan - Able to understand the objectives and risks of the research and to give dated and signed informed consent - Subject who has been informed of the results of the prior medical examination - Subject with a \"health pass\" in relation to the SARS-Cov2 pandemic as defined by current legislation, if applicable - Subject agreeing not to consume narcotics during the study (except tobacco and alcohol) - For a woman of childbearing age: *blood pregnancy test prescribed at inclusion, the result of which must be negative before taking the study treatment *effective contraception throughout the study *and agreement to perform a urine pregnancy test before each MRI"}
• {"criterion_text":"Group A: ADHD patients without associated mood disorder (ADHD-P) - 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. - Subjects benefiting or not from a methylphenidate treatment"}
• {"criterion_text":"Group B: patients with attention deficit due to/accentuated by mood disorders (ADHD-HD) - Association of ADHD symptoms with attentional disorders according to the combination of the following criteria: * DSM-5 diagnosis of recurrent depressive disorder or bipolar disorder *Currently euthymic, i.e., a QIDS-16 depression score < 6 (Appendix 1) and a YRMS mania score < 6 (Appendix 2), and clinically stabilized for at least 6 weeks prior to inclusion (stable treatment and out of acute phase). NB: for QIDS item 10 (concentration/decision making, score only decision making) *Criterion A of adult ADHD according to DSM-5 (at least 5 symptoms of inattention and/or hyperactivity/impulsivity) *Absence of Criterion D in childhood, adolescence and prior to mood disorders (i.e., absence of significant impact with reduced social, academic or occupational functioning) *Criterion D present (symptoms have a significant impact with reduced social, academic or occupational functioning) - Whether or not the subject is receiving treatment for mood disorders that is approved for: *mood stabilizers (lithium, valproate, lamotrigine, oxcarbazepine), *antidepressants (SSRIs, SNRIs ≤150mg/d venlafaxine and ≤60mg/d duloxetine), benzodiazepines at stable doses for more than one month (maximum daily dose of 10mg diazepam equivalent). - Subjects with or without methylphenidate treatment"}
• {"criterion_text":"Group C: healthy control subjects - Subjects with no psychiatric or neurological history"}

Exclusion criteria

• {"criterion_text":"Common criteria for all groups - Subject with a contraindication to methylphenidate: * hypersensitivity to the active substance, * glaucoma * pheochromocytoma, * treatment with other indirect sympathomimetics or alpha sympathomimetics (oral and/or nasal), irreversible MAOIs * Hyperthyroidism or thyrotoxicosis, * Pre-existing cardiovascular disorders including severe hypertension, XML File Identifier: 0Vmd7NrSRK8JeP+9ISLPaO9Oq+U= Page 12/26 heart failure, arterial occlusive disease, angina pectoris, congenital heart disease with hemodynamic impact, cardiomyopathy, myocardial infarction, arrhythmias and potentially life-threatening channelopathies (disorders caused by ion channel dysfunction), * Pre-existing cerebrovascular disorders, cerebral aneurysms, vascular abnormalities including vasculitis or stroke, * wheat allergy (other than celiac disease) - Unstabilized psychiatric disorders: severe depression, anorexia nervosa or anorexic disorder, suicidal tendencies, psychotic symptoms, severe mood disorders, mania, schizophrenia, psychopathic or borderline personality disorder - Family history of ventricular arrhythmia, sudden death, particularly of cardiac origin, or unexplained death - Subjects with a contraindication to MRI: presence of a non-removable ferromagnetic body, prosthesis, pacemaker, medication delivered by an implanted pump, vascular clip or stent, heart valve or ventricular bypass - History that may affect brain anatomy or be related to an abnormality (neonatal distress, neurosurgical operation, comitiveness, stroke, head injury with loss of consciousness of more than 15 minutes and mental retardation) - History that may affect brain function (general anesthesia or electroconvulsive therapy within 3 months prior to inclusion) - Substance use disorder, according to DSM-5 criteria (excluding tobacco) - Pregnant women or, in women of childbearing age and capacity (not infertile), lack of effective contraception - Subjects participating in other research involving an investigational product - Nursing women - Serious or unstabilized somatic pathology. - Subject deprived of liberty, or under forced care - Incapacitated subject (subject to a legal protection measure: curatorship, guardianship, future protection mandate, family habilitation) - Impossibility to give the subject informed information (subject in an emergency situation, difficulties in understanding the subject, ...) - Subject in a period of exclusion defined by another protocol in progress"}
• {"criterion_text":"Group A: ADHD patients without associated mood disorder (ADHD-P) • Current Mood Disorder • History of bipolar disorder in a first-degree relative • Taking unauthorized psychotropic drugs: all antidepressants, antipsychotics, sedative antihistamines, regular hypnotics, benzodiazepines in unstable doses."}
• {"criterion_text":"Group B: Patients with attention deficit disorder due to/ accentuated by mood disorders (ADHD-MD) • Acute phase of mood disorder defined by scores a depression score in the QIDS-16SC ≥ 6 and a mania score in the YRMS ≥ 6. NB: for ISQ item 10 (concentration/decision making, score decision making only). • Use of unauthorized psychotropic drugs including antipsychotics, sedative antihistamines, high-dose IRSNa (>150mg/d venlafaxine and >60mg/d duloxetine), MAOIs, tricyclic antidepressants, benzodiazepines in unstable doses."}
• {"criterion_text":"Group C: healthy subjects control - Taking any psychotropic medication (seasonal allergy treatments permitted)"}

Primary endpoints

• {"endpoint_text":"- Effect of methylphenidate on the task vs. rest in a region defined by its involvement in the cognitive task and its reactivity to methylphenidate. ROI (Region of Interest) analysis to maximize power.","definition_or_measurement_approach":"ROI analysis comparing task vs. rest activation in brain regions defined by involvement in the cognitive task and reactivity to methylphenidate (Region of Interest analysis to maximize power)."}

Secondary endpoints

• {"endpoint_text":"- Decrease in rCBF (regional Cerebral Blood Flow) in the methylphenidate condition vs. placebo, in the different groups.","definition_or_measurement_approach":"Comparison of regional cerebral blood flow (rCBF) between methylphenidate and placebo conditions across groups."}
• {"endpoint_text":"- Improved cognitive performance on tests of sustained attention, working memory and flexibility following the administration of methylphenidate, in the different groups.","definition_or_measurement_approach":"Cognitive tests measuring sustained attention, working memory and cognitive flexibility pre- and post-administration of methylphenidate versus placebo."}
• {"endpoint_text":"- Stabilization of the power of the EEG spectrum in the low frequencies (delta (1-4Hz) and theta (4-8Hz)) in the methylphenidate condition vs. placebo.","definition_or_measurement_approach":"EEG spectral power analysis in delta and theta bands comparing methylphenidate vs. placebo conditions."}
• {"endpoint_text":"- MRI: Interaction group x treatment x task on cerebral activation linked to sustained attention and linked to the inhibition corresponding to each of these tasks.","definition_or_measurement_approach":"MRI analysis of interaction effects (group x treatment x task) on cerebral activation related to sustained attention and inhibition."}
• {"endpoint_text":"- EEG: Group x treatment x task interaction on the amplitude of the P300 wave linked to sustained attention (P300b) and linked to inhibition (P300a) corresponding to each of these tasks.","definition_or_measurement_approach":"EEG P300 amplitude analysis (P300b and P300a) assessing group x treatment x task interactions."}

France

Earliest CTIS Part Ii Submission Date

09-09-2024

Latest Decision Or Authorization Date

19-09-2024

Processing Time Days

10

Number Of Sites

2

Number Of Participants

80

Primary sponsor

Full Name

Les Hopitaux Universitaires De Strasbourg

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France