Safety and Efficacy of Mexidol® for ADHD in Children Aged 6-12

Pharmasoft333 enrolled

Overview

The primary objective of this study was to evaluate the efficacy and safety of Mexidol® film-coated tablets (125 mg) compared to a placebo in children aged 6 to 12 years with Attention Deficit Hyperactivity Disorder (ADHD). This multicenter, prospective, double-blind, randomized trial included 333 children who met the diagnostic criteria established by the International Classification of Diseases (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Participants received either Mexidol or placebo for 42 days, and various efficacy and safety parameters were assessed.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

333

Conditions

Attention Deficit Hyperactivity Disorder (ADHD)Anxiety Disorders and Symptoms

Interventions

Eligibility

Sex: ALLMin age: 6 YearsMax age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed written informed consent for participation in the study from the patient's parents. 2. Patients - boys and girls aged 6 to 12 years, inclusive, at the time of signing the informed consent. 3. The child is raised by a father and/or mother. 4. The child is attending general education preschool or school institutions. 5. Diagnosis of Attention Deficit Hyperactivity Disorder (ADHD) established in accordance with ICD-10 and DSM-5 criteria by a psychiatrist or neurologist, specifically: \- According to DSM-5: 1. Six or more symptoms of inattention persisting for at least 6 months and/or 2. Six or more symptoms of hyperactivity and impulsivity persisting for at least 6 months 3. Symptoms are present in at least two areas of functioning (in preschool or school and at home). \- And/or according to ICD-10: 4. Presence of at least 6 symptoms of inattention 5. Presence of at least 3 symptoms of hyperactivity 6. Presence of at least 1 symptom of impulsivity 7. Persisting for at least 6 months. 6. Moderate severity of ADHD as determined by the Clinical Global Impression - Severity Scale for ADHD (CGI-ADHD-S), not requiring hospitalization for treatment. 7. No more than two comorbid disorders that do not require additional pharmacotherapy, in the investigator's opinion, during the study period. Exclusion Criteria: Individuals who exhibit at least one of the following characteristics were not included in the study: 1. Increased sensitivity to the active substance of the investigational drug (ethylmethylhydroxypyridine succinate) and/or other components of the drug. 2. Liver dysfunction: ALT and/or AST ≥2.5 times the upper limit of normal (ULN) based on screening lab results. 3. Kidney dysfunction: serum creatinine ≥1.5 times ULN based on screening lab results. 4. Intracranial pathology (including but not limited to: intracranial hemorrhage, tumors, infections, history of head trauma, excluding concussion). 5. Co-occurring autism spectrum disorders, Asperger syndrome. 6. Intellectual disability of any degree. 7. Other mental disorders, except for behavioral disorders (ICD-10 code F91). 8. Inability to discontinue psychotropic medications used for the treatment of ADHD. 9. Other somatic and/or neurological disorders requiring treatment with medications that may affect the efficacy of the investigational drug (including but not limited to: epilepsy, depression). 10. Use of nootropic, vasoactive medications, neuroprotectors, antioxidants, or metabolic agents within 7 days or 5 half-lives (whichever is longer) prior to randomization. 11. Presence of any oncological disease in the medical history within 5 years prior to the screening visit. 12. Participation in any other clinical study of drugs and/or medical devices within 3 months prior to the screening visit and/or 5 half-lives, whichever is longer. 13. Inability or unwillingness to comply with protocol requirements, including for physical, mental, or social reasons, in the opinion of the investigator. 14. Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Locations (14)

State Autonomous Healthcare Institution of the Sverdlovsk Region "Multispecialty Clinical Medical Center 'Bonum'

Yekaterinburg, Ural Region, Russia

Federal State Budgetary Educational Institution of Higher Education "Kazan State Medical University" Ministry of Health of the Russian Federation

Kazan', Russia

State Budgetary Healthcare Institution "Specialized Clinical Psychiatric Hospital №1" of the Ministry of Health of the Krasnodar Territory

Krasnodar, Russia

Limited Liability Company "Center for Professional Therapy"

Krasnodar, Russia

Federal State Autonomous Educational Institution of Higher Education "Russian National Research Medical University named after N.I. Pirogov" Ministry of Health of the Russian Federation

Moscow, Russia

State Budgetary Healthcare Institution of the City of Moscow "Scientific and Practical Center for Child Psychoneurology of the Moscow Department of Healthcare"

Moscow, Russia

Limited Liability Company "NizhMedClinic"

Nizhny Novgorod, Russia

State Budgetary Healthcare Institution "Orenburg Regional Clinical Psychiatric Hospital №1"

Orenburg, Russia

Limited Liability Company "Medical Technologies"

Saint Petersburg, Russia

Limited Liability Company "DNA Research Center"

Saratov, Russia

...and 4 more locations

Outcomes

Primary Outcomes

The Average Change in the Total Score Across the "Inattention" and "Hyperactivity/Impulsivity" Subscales of the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) After 6 Weeks of Therapy Compared to the Baseline Level.

The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder and oppositional defiant disorder symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores are calculated by summing the scores on the subset and dividing by the number of items in the subset. The main criterion for the treatment efficacy was the mean change in the total score on the "inattention" and "hyperactivity/impulsivity" subscales after 6 weeks of therapy. A conclusion of superiority of Mexidol over placebo can be made if the upper limit of the 95% confidence interval for the difference in mean changes is negative. 55 point scale: min value 0, max value 54, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day 1 = Randomization Visit)

Secondary Outcomes

Average Change in the the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV), Subscale "Inattention"

The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores on the SNAP-IV are calculated by summing the scores on the subset and dividing by the number of items in the subset. The score for any subset is expressed as the Average Rating-Per-Item. 28 point scale: min value 0, max value 27, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 1 Day 0 = Screening)

Average Change in the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV), Subscale "Hyperactivity/Impulsivity"

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 1 Day 0 = Screening)

Average Change in the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV), Subscale "Oppositional Defiant Disorder"

The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores on the SNAP-IV are calculated by summing the scores on the subset and dividing by the number of items in the subset. The score for any subset is expressed as the Average Rating-Per-Item. 25 point scale: min value 0, max value 24, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 1 Day 0 = Screening)

Average Change in the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV), Subscale "Connors Index"

The Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV) is a 90-question self-report inventory designed to measure attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) symptoms in children and young adults. The SNAP-IV is based on a 0 to 3 rating scale: Not at all = 0, Just a little = 1, Often = 2, and Very often = 3. The questions measure different domains of ADHD and ODD. Subscale scores on the SNAP-IV are calculated by summing the scores on the subset and dividing by the number of items in the subset. The score for any subset is expressed as the Average Rating-Per-Item. 31 point scale: min value 0, max value 30, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 1 Day 0 = Screening)

Average Change in the Spence Children's Anxiety Scale - Parent Version (SCAS-Parent) Score

The Spence Children's Anxiety Scale - Parent Version (SCAS-Parent) is a 39-item parent report measure designed to assess anxiety symptoms in children. Built upon contemporary diagnostic frameworks, the SCAS-Parent evaluates six distinct domains of anxiety that align with clinical diagnostic categories. Each question on the test addresses the frequency of certain anxiety symptoms, measured on a 0-3 scale from "never", "sometimes", "often", to "always". SCAS-Parent scores consist of a total raw score (range from 0 to 114) and six sub-scale scores, with higher scores indicating greater severity of anxiety symptoms. 124 point scale: min value 0, max value 123, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day 1 = Randomization Visit)

Average Change in the Attention Deficit Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) Score

The Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) is an 18-question inventory used to aid in the diagnosis of attention deficit hyperactivity disorder (ADHD) in children. Each question measures the frequency of the behavior on a 0-3 scale from "rarely or never", "sometimes", "often", to "very often". The questionnaire is intended to be filled out by parents and teachers. Higher scores indicate greater severity of ADHD symptoms. 55 point scale: min value 0, max value 54, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day 1 = Randomization Visit)

Assessment Using the Clinical Global Impressions for Attention Deficit Hyperactivity Disorder Severity (CGI-ADHD-S) Scale

The Clinical Global Impressions-ADHD-Severity (CGI-ADHD-S) is a clinician-rated scale used to assess the severity of Attention Deficit Hyperactivity Disorder (ADHD) symptoms. This tool is part of the Clinical Global Impressions (CGI) scales. It typically consists of a single item that rates the severity of ADHD on a 7-point scale, ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). 7 point scale: min value 1, max value 7, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day 1 = Randomization Visit)

Assessment Using the Clinical Global Impressions Scale for Improvement (CGI-I)

The Clinical Global Impressions (CGI) Scale is a standardized assessment tool used to rate the severity of illness, change over time, and efficacy of medication. It consists of 3 subscales. The subscale Clinical Global Impression-Improvement (CGI-I) is a 7-point scale that assesses how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention, and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. 7 point scale: min value 1, max value 7, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (before treatment)

Assessment Using the Pediatric Migraine Disability Assessment Questionnaire (PedMIDAS), Days

The Pediatric Migraine Disability Assessment questionnaire (PedMIDAS) is used to assess the impact of headaches on school performance (three questions), activities at home (one question on homework or chores), and social and/or sports functions (two questions). The PedMIDAS is scored by summing the answers across the six questions. The frequency and severity are not scored but can be used for clinical reference. PedMIDAS score range from 0 to 10 indicates little to none disability grade, score range from 11 to 30 indicates mild disability grade, score range from 31 to 50 indicates moderate disability grade and score range greater than 50 indicates severe disability grade. Min value 0, max value 240, higher scores mean a worse outcome.

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day1 = Randomization Visit)

Assessment Using the Pediatric Migraine Disability Assessment Questionnaire (PedMIDAS), Headache Severity

Time frame: Visit 5 (after 6 weeks of therapy) compared to the baseline level (Visit 2 Day1 = Randomization Visit)