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NCT Number: NCT07417878

Study of the Nutritional, Inflammatory, and Metabolic Endophenotypes of Attention-Deficit/Hyperactivity Disorder (ADHD)

This study aims to better understand the biological mechanisms involved in attention deficit hyperactivity disorder (ADHD) and to clarify why some children and adolescents respond well to methylphenidate (MPH)-the most commonly prescribed medication-while others do not. Although MPH is effective for many patients, a significant number experience limited benefits or problematic side effects such as appetite loss and sleep difficulties. Recent research suggests that inflammation and oxidative stress in the body may play an important role in ADHD. Some animal studies also indicate that MPH itself might trigger inflammatory processes, but this has never been examined directly in humans.

The main goal of this research is to determine whether children with ADHD show differences in their nutritional, immune, and inflammatory profiles compared to children without ADHD, and whether these biological factors influence symptom severity, digestive problems, and response to treatment. The study also seeks to understand whether MPH has a measurable inflammatory effect in young patients and whether this could be linked to treatment tolerability.

To answer these questions, the study combines several approaches. First, a case-control comparison will examine differences between children/adolescents with ADHD and age- and sex-matched controls. Second, a one-year follow-up of the ADHD group will evaluate changes over time and help identify biological predictors of treatment response and side effects. Finally, a cross-sectional analysis will investigate the role of polyphenols-natural antioxidant compounds found in food-in relation to inflammation, treatment outcomes, and gender differences.

The primary focus is on comparing levels of the inflammatory marker IL-6 between children with ADHD and controls. Secondary objectives include assessing additional inflammatory and immune indicators, nutritional status, gastrointestinal symptoms, ADHD severity, irritability, and MPH tolerability.

By identifying specific inflammatory and immune markers associated with ADHD and treatment response, this study hopes to improve understanding of the disorder and guide more personalized and effective treatment strategies for young patients. It will also provide the first human data on whether psychostimulant medications may have inflammatory effects.

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Key information

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

ADHD Group (Cases) - Inclusion Criteria:

  • Children or adolescents aged 7 to 17 years.
  • Meet DSM-5 diagnostic criteria for Attention-Deficit/Hyperactivity Disorder (ADHD), assessed using the K-SADS interview.
  • Currently treated with psychostimulant medication.
  • Stabilized on psychostimulant treatment for at least one month prior to inclusion.
  • Signed informed consent obtained from parents or legal guardians.
  • Assent obtained from the minor participant.
  • Affiliation with a national health insurance system.

Control Group (Typically Developing Peers) - Inclusion Criteria:

  • Children or adolescents aged 7 to 17 years without any diagnosed mental disorder.
  • Age- and sex-matched with the ADHD group.
  • Signed informed consent obtained from parents or legal guardians.
  • Assent obtained from the minor participant.
  • Affiliation with a national health insurance system.

ADHD Group (Cases) - Exclusion Criteria:

  • Presence of a progressive neurological disorder, intellectual developmental disorder, or clinically significant suicide risk.
  • Presence of an immunological or chronic inflammatory disease.
  • Inability to comply with medication-free periods of at least two weeks.
  • Absence of parental consent.
  • Absence of assent from the minor participant.
  • Participation in another clinical study with an ongoing exclusion period.

Control Group (Typically Developing Peers) - Exclusion Criteria:

  • Presence of an immunological or chronic inflammatory disease.
  • Absence of parental consent.
  • Absence of assent from the minor participant.
  • Participation in another clinical study with an ongoing exclusion period.

Treatment and study plan

Clinical and Biological Evaluation - ADHD Cases

Other

Children and adolescents with ADHD undergo diagnostic confirmation (K-SADS if not completed within 6 months), behavioral and functional questionnaires (ADHD-RS for cases only, P-ARI, R4PDQ, KIDMED), clinician-rated scales (CGI-S/I, PAERS), and venous blood sampling for plasma and PBMC analysis. They complete two assessments: one during stabilized medication and one after a minimum two-week medication interruption, consistent with clinical practice guidelines. Assessments occur during the school period to reduce confounding factors.

Clinical and Biological Evaluation - Controls

Other

Children and adolescents without psychiatric disorders undergo behavioral and functional questionnaires (P-ARI, R4PDQ, KIDMED)and venous blood sampling for plasma and PBMC analysis.

Primary outcomes

  1. Circulating IL-6 Levels in ADHD vs. Controls

    Time frame: Baseline (V1)

    Comparison of IL-6 levels between children and adolescents with ADHD and age- and sex-matched typically developing controls at baseline (V1).

Secondary outcomes

  1. CRP Levels in ADHD vs. Controls

    Time frame: Baseline (V1)

    Comparison of CRP levels between ADHD participants and matched controls at V1.

  2. IL-1β Levels in ADHD vs. Controls

    Time frame: Baseline (V1)

    Comparison of IL-1β levels between ADHD participants and matched controls at V1.

  3. IL-6 Levels in ADHD vs. Controls

    Time frame: Baseline (V1)

    Comparison of IL-6 levels between ADHD participants and matched controls at V1.

  4. IL-10 Levels in ADHD vs. Controls

    Time frame: Baseline (V1)

    Comparison of IL-10 levels between ADHD participants and matched controls at V1.

  5. TNF-α Levels in ADHD vs. Controls

    Time frame: Baseline (V1)

    Comparison of TNF-α levels between ADHD participants and matched controls at V1.

  6. NfL Levels in ADHD vs. Controls

    Time frame: Baseline (V1)

    Comparison of NfL levels between ADHD participants and matched controls at V1.

  7. CRP Levels in Medicated vs. Unmedicated ADHD Participants

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Comparison of CRP levels in ADHD participants during medicated vs. unmedicated periods (V1 vs. V2).

  8. IL-1β Levels in Medicated vs. Unmedicated ADHD Participants

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Comparison of IL-1β levels in ADHD participants during medicated vs. unmedicated periods (V1 vs. V2).

  9. IL-6 Levels in Medicated vs. Unmedicated ADHD Participants

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Comparison of IL-6 levels in ADHD participants during medicated vs. unmedicated periods (V1 vs. V2).

  10. IL-10 Levels in Medicated vs. Unmedicated ADHD Participants

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Comparison of IL-10 levels in ADHD participants during medicated vs. unmedicated periods (V1 vs. V2).

  11. TNF-α Levels in Medicated vs. Unmedicated ADHD Participants

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Comparison of TNF-α levels in ADHD participants during medicated vs. unmedicated periods (V1 vs. V2).

  12. NfL Levels in Medicated vs. Unmedicated ADHD Participants

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Comparison of NfL levels in ADHD participants during medicated vs. unmedicated periods (V1 vs. V2).

  13. Pro- and Anti-Inflammatory Cytokine Plasma Levels for Immuno-Inflammatory Biotype Identification in ADHD patients

    Time frame: Baseline (V1)

    Exploration of the existence of distinct immuno-inflammatory profiles among children and adolescents with ADHD using unsupervised clustering methods to define High Inflammatory Profile vs Low Inflammatory Profile. Participants with ADHD will be categorized into distinct biotypes (High Inflammatory vs. Low Inflammatory) determined by the integrated analysis of pro- and anti-inflammatoru cytokines. Plasma levels of IL-6, IL-1β, IL-10, and TNF-α will be measured in pg/mL.

    These biomarkers will contribute to the identification of High vs Low inflammatory biotypes using unsupervised clustering methods.

  14. C-Reactive Protein (CRP) Levels for Immuno-Inflammatory Biotype Identification in ADHD patients

    Time frame: Baseline (V1)

    Exploration of the existence of distinct immuno-inflammatory profiles among children and adolescents with ADHD using unsupervised clustering methods to define High Inflammatory Profile vs Low Inflammatory Profile. Participants with ADHD will be categorized into distinct biotypes (High Inflammatory vs. Low Inflammatory) determined by the integrated analysis of acute phase reactants. C-reactive protein (CRP) levels will be measured in mg/L.

    These biomarkers will contribute to the identification of High vs Low inflammatory biotypes using unsupervised clustering methods.

  15. Neurofilament Light Chain (NfL) Levels for Immuno-Inflammatory Biotype Identification in ADHD patients

    Time frame: Baseline (V1)

    Exploration of the existence of distinct immuno-inflammatory profiles among children and adolescents with ADHD using unsupervised clustering methods to define High Inflammatory Profile vs Low Inflammatory Profile. Participants with ADHD will be categorized into distinct biotypes (High Inflammatory vs. Low Inflammatory) determined by the integrated analysis of a neuronal injury marker. Neurofilament Light chain (NfL) levels will be measured in pg/mL.

    These biomarkers will contribute to the identification of High vs Low inflammatory biotypes using unsupervised clustering methods.

  16. Correlations between Immuno-Inflammatory Profiles & ADHD Symptoms

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL) and ADHD symptoms using the Attention Deficit Hyperactivity Disorder Rating Scale 'ADHD-RS'

  17. Correlations between Immuno-Inflammatory Profiles & Gastrointestinal Symptoms

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL) and gastrointestinal symptoms using the Rome IV Pediatric Diagnostic Questionnaire 'R4DQ-child'.

  18. Correlations between Immuno-Inflammatory Profiles & Treatment Tolerability/Effectiveness

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL) and treatment tolerability/effectiveness using the Pediatric Adverse Event Rating Scale 'PAERS'.

  19. Correlations between Immuno-Inflammatory Profiles & Treatment Tolerability/Effectiveness

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL) and treatment tolerability/effectiveness using the Visual Analog Scale 'VAS'.

  20. Correlations between Immuno-Inflammatory Profiles & Irritability

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL) and irritability using the Parental Affective Reactivity Index 'ARI-P'.

  21. Nutritional Profiles in ADHD vs. Controls

    Time frame: Baseline (V1)

    Comparison of nutritional profiles assessed using the Mediterranean Diet Quality Index in children and adolescents 'KIDMED' between children and adolescents with ADHD and age- and sex-matched typically developing peers.

  22. Correlations between Nutritional and Immuno-Inflammatory profiles

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between nutritional profiles - using the Mediterranean Diet Quality Index in children and adolescents 'KIDMED' - and the immuno-inflammatory profiles (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL).

  23. Correlations between Polyphenol Bioavailability & ADHD symptoms

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations of polyphenol bioavailability - using a 3-day food-tracking diary and the Phenol-Explorer database - with ADHD symptoms using the Attention Deficit Hyperactivity Disorder Rating Scale 'ADHD-RS'.

  24. Correlations between Polyphenol Bioavailability & Irritability

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between polyphenol bioavailability - using a 3-day food-tracking diary and the Phenol-Explorer database - with irritability using the Parental Affective Reactivity Index 'ARI-P').

  25. Correlations between Polyphenol Bioavailability & Immuno-Inflammatory Markers

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between polyphenol bioavailability - using a 3-day food-tracking diary and the Phenol-Explorer database - with immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL).

  26. Correlations between Polyphenol Bioavailability & Treatment Tolerability/Effectiveness

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between polyphenol bioavailability - using a 3-day food-tracking diary and the Phenol-Explorer database - with psychostimulant treatment tolerability/effectiveness using the Pediatric Adverse Event Rating Scale 'PAERS'.

  27. Correlations between Polyphenol Bioavailability & Treatment Tolerability/Effectiveness

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between polyphenol bioavailability - using a 3-day food-tracking diary and the Phenol-Explorer database - with psychostimulant treatment tolerability/effectiveness using the Visual Analog Scale 'VAS'.

  28. Correlations between Immuno-Inflammatory Profiles & ADHD Symptoms

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL) and ADHD symptoms using the Attention Deficit Hyperactivity Disorder Rating Scale 'ADHD-RS'.

  29. Correlations between Immuno-Inflammatory Profiles & Irritabiliy

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL) and irritabiliy using the Parental Affective Reactivity Index 'ARI-P'.

  30. Correlations between immuno-inflammatory markers and ADHD symptoms

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between immuno-inflammatory markers (CRP, IL-6, IL-1β, IL-10, TNF-α, and NfL) and ADHD symptoms using Clinical Global Impression 'CGI'.

  31. Correlations between nutritional profiles and ADHD symptoms

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between nutritional profiles - using the Mediterranean Diet Quality Index in children and adolescents 'KIDMED' - and clinical symptoms using the Attention Deficit Hyperactivity Disorder Rating Scale 'ADHD-RS'.

  32. Correlations between nutritional profiles and overall clinical symptoms

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations between nutritional profiles - using the Mediterranean Diet Quality Index in children and adolescents 'KIDMED' - and overall clinical symptoms using Clinical Global Impression 'CGI'.

  33. Correlations between Polyphenol Bioavailability & overall clinical symptoms

    Time frame: Baseline (V1) and Follow-up (V2)(up to 6-months after V1)

    Examination of correlations of polyphenol bioavailability using a 3-day food-tracking diary and the Phenol-Explorer database with overall clinical symptoms using Clinical Global Impression 'CGI'.

Study contacts

Contact information is provided by the study sponsor or research team.

Diane PURPER-OUAKIL, PUPH

CONTACT

[email protected]

+ 33 467336009 Ext. +33

Sponsors and collaborators

Lead sponsor

University Hospital, Montpellier

Other

Collaborators

  • INRAE Bordeaux

Registry information

Acronym: ANIME

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Feb 18, 2026
Registry last updated
Feb 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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