Effectiveness of Neuroplasticity-Targeted Supplements on Neuroinflammatory Markers, ADHD Symptom Severity, and Clinical Scores in Children

Официальное название

Effectiveness of Neuroplasticity-Targeted Supplements on Neuroinflammatory Markers, ADHD Symptom Severity, and Clinical Scores in Children: A Randomized Controlled Trial

Обзор

This randomized controlled trial will evaluate the effectiveness of neuroplasticity-targeted supplements on neuroinflammatory markers and ADHD symptoms in children aged 6 to 12 years diagnosed with Attention Deficit Hyperactivity Disorder (ADHD). Participants will be randomly assigned to one of four groups: gut-targeted supplements (prebiotics and probiotics), brain-targeted supplements (omega-3 fatty acids and vitamin B1), combined supplementation, or placebo. The intervention period will last 12 weeks. Primary outcomes include changes in ADHD symptom severity and clinical scores using validated rating scales. Secondary outcomes include changes in biomarkers of neuroinflammation and neuroplasticity, including IL-6, TNF-alpha, BDNF, short-chain fatty acids, and Claudin-5.

Подробное описание

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. Emerging evidence suggests that neuroinflammation, altered gut microbiota, and impaired neuroplasticity may contribute to ADHD pathophysiology. Nutritional interventions that target these mechanisms may provide additional therapeutic benefit.

This study is a randomized, placebo-controlled, parallel-group clinical trial designed to investigate whether supplementation with prebiotics, probiotics, omega-3 fatty acids, and vitamin B1 can improve ADHD symptoms and related biological markers in children. Sixty-eight participants aged 6 to 12 years with DSM-5 confirmed ADHD will be enrolled and randomly assigned in equal numbers to one of four intervention groups: (1) prebiotics plus probiotics, (2) omega-3 fatty acids plus vitamin B1, (3) combined supplementation, or (4) placebo.

The intervention duration will be 12 weeks. ADHD symptoms and behavioral scores will be assessed at baseline and after treatment using validated rating scales, including Conners 3 and Vanderbilt ADHD forms. Blood samples will be collected at baseline and week 12 for measurement of inflammatory and neuroplasticity biomarkers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), brain-derived neurotrophic factor (BDNF), short-chain fatty acids (SCFA), Claudin-5, and complete blood count parameters.

The primary objective is to determine the effect of supplementation on ADHD symptom scores. Secondary objectives include comparison of treatment groups for biomarker changes and evaluation of associations between biological markers and clinical outcomes. Results may help identify safe adjunctive nutritional strategies for children with ADHD.

Вмешательства

• Пищевая добавка Inulin
  Participants will receive inulin powder 6 grams orally once daily for 12 weeks as a prebiotic supplement intended to support beneficial gut microbiota.
• Пищевая добавка Probiotic
  Participants will receive a probiotic supplement containing Acidophilus Bifidus 2 × 10\^11 CFU orally once daily for 12 weeks.
• Пищевая добавка Omega-3 Fatty Acids
  Participants will receive omega-3 fatty acid supplementation containing EPA 650 mg and DHA 540 mg orally once daily for 12 weeks.
• Пищевая добавка Thiamine
  Participants will receive thiamine (vitamin B1) 10 mg orally once daily for 12 weeks.
• Другое Placebo
  Participants will receive matching placebo supplementation orally once daily for 12 weeks.

Первичные конечные точки

• Parent and Teacher ADHD Rating [Срок оценки: Baseline and Week 12]
• Neuroinflammation Markers (IL-6, TNF-α) [Срок оценки: Baseline and Week 12]
• Neuroplasticity Markers (BDNF, Claudin-5) [Срок оценки: Baseline and Week 12]
• Short-Chain Fatty Acids (SCFA) [Срок оценки: Baseline and Week 12]
• Complete Blood Count (CBC) [Срок оценки: Baseline and Week 12]
• ADHD Diagnostic Parent and Teacher Rating [Срок оценки: Baseline and Week 12]

Критерии участия

Критерии включения

• DSM-5 confirmed ADHD diagnosis
• Age 6-12 years
• Medication-free or on stable stimulant medication (≥1 month)

Критерии исключения

• Antibiotic use in last 4 weeks
• Gastrointestinal disorders
• Neurological comorbidities (e.g., epilepsy)
• Severe food allergies

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Пакистан · 1 центр

• Khyber Teaching Hospital — Peshawar

Публикации

• Allahyari P, Abbas Torki S, Aminnezhad Kavkani B, Mahmoudi Z, Mousavi Hoseini MS, Moradi M, Alami F, Keshavarz Mohammadian M, Bahoo Sele Bani S, Abbasi Mobarakeh K, Shafaei H, Khoshdooz S, Hajipour A, Doaei S, Gholamalizadeh M. A systematic review of the beneficial effects of prebiotics, probiotics, and synbiotics on ADHD. Neuropsychopharmacol Rep. 2024 Jun;44(2):300-307. doi: 10.1002/npr2.12437. PMID 38623929
• Levy Schwartz M, Magzal F, Yehuda I, Tamir S. Exploring the impact of probiotics on adult ADHD management through a double-blind RCT. Sci Rep. 2024 Nov 5;14(1):26830. doi: 10.1038/s41598-024-73874-y. PMID 39500949
• Yin X, Liu W, Feng H, Huang J, Wang Q, Zhang Q, He J, Wang R. Bifidobacterium animalis subsp. lactis A6 attenuates hippocampal damage and memory impairments in an ADHD rat model. Food Funct. 2024 Mar 4;15(5):2668-2678. doi: 10.1039/d3fo04665f. PMID 38374797
• Checa-Ros A, Jerez-Calero A, Molina-Carballo A, Campoy C, Munoz-Hoyos A. Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications. Nutrients. 2021 Jan 16;13(1):249. doi: 10.3390/nu13010249. PMID 33467150
• Sayed SZ, Hassan ZO, Abdelraheem WM, Refaat RS, Abuelela IS. Is there a link between peripheral inflammation and blood brain barrier integrity in children with attention-deficit/hyperactivity disorder? A case-control study. BMC Pediatr. 2024 Nov 26;24(1):769. doi: 10.1186/s12887-024-05254-4. PMID 39592970
• Steckler R, Magzal F, Kokot M, Walkowiak J, Tamir S. Disrupted gut harmony in attention-deficit/hyperactivity disorder: Dysbiosis and decreased short-chain fatty acids. Brain Behav Immun Health. 2024 Jul 27;40:100829. doi: 10.1016/j.bbih.2024.100829. eCollection 2024 Oct. PMID 39184374
• Young GS, Conquer JA, Thomas R. Effect of randomized supplementation with high dose olive, flax or fish oil on serum phospholipid fatty acid levels in adults with attention deficit hyperactivity disorder. Reprod Nutr Dev. 2005 Sep-Oct;45(5):549-58. doi: 10.1051/rnd:2005045. PMID 16188207

Идентификаторы

NCT: NCT07665658 · KMU/DIR/CTU/2026/02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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