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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Attention Deficit Hyperactivity Disorder
• Intervention / Treatment: Dietary supplement: Inulin; Dietary supplement: Probiotic; Dietary supplement: Omega-3 Fatty Acids; Dietary supplement: Thiamine; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 68
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Dur E Shawar, PhD*; Phone Number: 03348405894; Email: shehwar88@gmail.com
• Study Contact Backup: Name: Prof Dr Inayat Shah, PhD; Phone Number: 03321431414; Email: inayat.shah@kmu.edu.pk

Study Locations

• Pakistan
  • KPK
    • Peshawar, KPK, Pakistan, 25000
      • Recruiting
      • Khyber Teaching Hospital
      • Contact: Dr Dur e
      • Contact: Dr Inayat Khan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gut-Targeted Supplements Group; Participants will receive prebiotics (inulin 6 g/day) and probiotics (Acidophilus Bifidus 2 × 10^11 CFU/day orally) for 12 weeks.	Dietary supplement: Inulin; Participants will receive inulin powder 6 grams orally once daily for 12 weeks as a prebiotic supplement intended to support beneficial gut microbiota.; Other Names: Fructan prebiotic; Dietary supplement: Probiotic; Participants will receive a probiotic supplement containing Acidophilus Bifidus 2 × 10^11 CFU orally once daily for 12 weeks.; Other Names: Acidophilus Bifidus
Experimental: Neuroplasticity-Targeted Supplements Group; Participants will receive omega-3 fatty acids containing EPA 650 mg and DHA 540 mg daily, plus vitamin B1 (thiamine 10 mg/day orally) for 12 weeks.	Dietary supplement: 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.; Other Names: Fish Oil, EPA, DHA; Dietary supplement: Thiamine; Participants will receive thiamine (vitamin B1) 10 mg orally once daily for 12 weeks.; Other Names: Vitamin B1
Experimental: Combined Supplements Group; Participants will receive prebiotics (inulin 6 g/day), probiotics (Acidophilus Bifidus 2 × 10^11 CFU/day), omega-3 fatty acids containing EPA 650 mg and DHA 540 mg daily, and vitamin B1 (thiamine 10 mg/day orally) for 12 weeks.	Dietary supplement: Inulin; Participants will receive inulin powder 6 grams orally once daily for 12 weeks as a prebiotic supplement intended to support beneficial gut microbiota.; Other Names: Fructan prebiotic; Dietary supplement: Probiotic; Participants will receive a probiotic supplement containing Acidophilus Bifidus 2 × 10^11 CFU orally once daily for 12 weeks.; Other Names: Acidophilus Bifidus; Dietary supplement: 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.; Other Names: Fish Oil, EPA, DHA; Dietary supplement: Thiamine; Participants will receive thiamine (vitamin B1) 10 mg orally once daily for 12 weeks.; Other Names: Vitamin B1
Placebo Comparator: Placebo Group; Participants will receive matching placebo supplements orally for 12 weeks.	Other: Placebo; Participants will receive matching placebo supplementation orally once daily for 12 weeks.; Other Names: Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parent and Teacher ADHD Rating	Change in Attention-Deficit/Hyperactivity Disorder (ADHD) symptom severity measured using the Conners 3 Parent and Teacher ADHD Rating Scales. The Conners 3 assesses inattention, hyperactivity/impulsivity, executive functioning, learning problems, aggression, and peer relations. Raw scores are converted to T-scores, with higher scores indicating greater symptom severity and functional impairment. Scale Information: T-score range: approximately 40-90 Higher scores indicate worse ADHD symptoms.	Baseline and Week 12
Neuroinflammation Markers (IL-6, TNF-α)	Change in serum levels of pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha measured by ELISA	Baseline and Week 12
Neuroplasticity Markers (BDNF, Claudin-5)	Change in brain-derived neurotrophic factor (BDNF) and blood-brain barrier tight junction protein claudin-5 measured by ELISA	Baseline and Week 12
Short-Chain Fatty Acids (SCFA)	Change in gut microbiota-derived metabolites (e.g., butyrate) measured by ELISA	Baseline and Week 12
Complete Blood Count (CBC)	Change in blood cell counts (e.g., white blood cells, red blood cells, platelets)	Baseline and Week 12
ADHD Diagnostic Parent and Teacher Rating	Change in ADHD symptom severity measured using the Vanderbilt ADHD Diagnostic Parent and Teacher Rating Scales. The symptom assessment includes 18 ADHD items corresponding to DSM criteria for inattentive and hyperactive-impulsive symptoms. Total symptom scores range from 0 to 54, with higher scores indicating greater ADHD symptom severity. Scale Information: Minimum score: 0 Maximum score: 54 Higher scores indicate worse ADHD symptoms.	Baseline and Week 12

Collaborators and Investigators

• Sponsor: Khyber Medical University Peshawar
• Collaborators: Khyber Teaching Hospital
• Investigators: Principal Investigator: Dr Dur E Shawar, PhD*, Khyber Medical University Peshawar, Pakistan; Principal Investigator: Prof Dr Inayat Shah, PhD, Khyber Medical University Peshawar, Pakistan; Principal Investigator: Prof Dr Omer Malik, PhD, Khyber Medical University Peshawar, Pakistan; Principal Investigator: Dr Madiha Khattak, PhD, Khyber Medical College

Publications and helpful links

General Publications

• 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. Epub 2024 Apr 16.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 25, 2026

Study Registration Dates

• First Submitted: June 16, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Neuroinflammation; Neuroplasticity; Attention Deficit Hyperactivity Disorder; Randomized Controlled Trial
• Additional Relevant MeSH Terms: Nervous System Diseases; Mental Disorders; Pathologic Processes; Inflammation; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Pathological Conditions, Signs and Symptoms; Neuroinflammatory Diseases; Attention Deficit Disorder with Hyperactivity; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Thiazoles; Azoles; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Carbohydrates; Carbohydrates; Pyrimidines; Polymers; Macromolecular Substances; Polysaccharides; Starch; Glucans; Fatty Acids, Unsaturated; Biopolymers; Fructans; Oils; Dietary Fats; Fats; Dietary Fats, Unsaturated; Thiamine; Probiotics; Inulin; Fish Oils; Fatty Acids, Omega-3
• Other Study ID Numbers: KMU/DIR/CTU/2026/02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD that underlie the results reported in publications, including demographic data, baseline characteristics, ADHD symptom scores, laboratory measurements, and intervention allocation data, will be shared after de-identification. Data will be provided in a manner that protects participant confidentiality and privacy. Supporting study documents including the study protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code will also be made available. IPD that underlie the results reported in publications, including demographic data, baseline characteristics, ADHD symptom scores, laboratory measures, and intervention allocation data, will be shared after de-identification. Data will be provided in a manner that protects participant confidentiality and privacy. Supporting study documents including the study protocol, statistical analysis plan, informed consent form, clinical study report, and analytic code will also be made available.
• IPD Sharing Time Frame: Data will become available beginning 6 months after publication of the primary study results and will remain available for 5 years thereafter.
• IPD Sharing Access Criteria: De-identified participant data and supporting documents will be made available to qualified researchers who provide a methodologically sound research proposal. Requests should be directed to the Principal Investigator. Access will be granted following review and approval of the proposal and execution of a data-sharing agreement that ensures participant confidentiality and compliance with applicable ethical and regulatory requirements.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No