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

NCT07665658 | Recruiting DMC

• 1 other identifier: KMU/DIR/CTU/2026/02
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

Attention Deficit Hyperactivity Disorder; Randomized Controlled Trial; Neuroinflammation; Neuroplasticity

Outcome Measures

Primary Outcomes (6)

• 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

Study Arms (4)

Gut-Targeted Supplements Group

EXPERIMENTAL

Participants will receive prebiotics (inulin 6 g/day) and probiotics (Acidophilus Bifidus 2 × 10\^11 CFU/day orally) for 12 weeks.

Dietary Supplement: Inulin; Dietary Supplement: Probiotic

Neuroplasticity-Targeted Supplements Group

EXPERIMENTAL

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; Dietary Supplement: Thiamine

Combined Supplements Group

EXPERIMENTAL

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; Dietary Supplement: Probiotic; Dietary Supplement: Omega-3 Fatty Acids; Dietary Supplement: Thiamine

Placebo Group

PLACEBO COMPARATOR

Participants will receive matching placebo supplements orally for 12 weeks.

Other: Placebo

Interventions

Inulin DIETARY_SUPPLEMENT

Participants will receive inulin powder 6 grams orally once daily for 12 weeks as a prebiotic supplement intended to support beneficial gut microbiota.

Also known as: Fructan prebiotic

Combined Supplements Group; Gut-Targeted Supplements Group

Thiamine DIETARY_SUPPLEMENT

Participants will receive thiamine (vitamin B1) 10 mg orally once daily for 12 weeks.

Also known as: Vitamin B1

Combined Supplements Group; Neuroplasticity-Targeted Supplements Group

Placebo OTHER

Participants will receive matching placebo supplementation orally once daily for 12 weeks.

Also known as: Matching placebo

Placebo Group

Probiotic DIETARY_SUPPLEMENT

Participants will receive a probiotic supplement containing Acidophilus Bifidus 2 × 10\^11 CFU orally once daily for 12 weeks.

Also known as: Acidophilus Bifidus

Combined Supplements Group; Gut-Targeted Supplements Group

Omega-3 Fatty Acids DIETARY_SUPPLEMENT

Participants will receive omega-3 fatty acid supplementation containing EPA 650 mg and DHA 540 mg orally once daily for 12 weeks.

Also known as: Fish Oil, EPA, DHA

Combined Supplements Group; Neuroplasticity-Targeted Supplements Group

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Khyber Medical University Peshawar: lead
• Khyber Teaching Hospital: collaborator

Study Sites (1)

Khyber Teaching Hospital

Peshawar, KPK, 25000, Pakistan

RECRUITING

Related Publications (7)

• 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.

  PMID: 38623929 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity; Neuroinflammatory Diseases

Interventions

Inulin; Probiotics; Fatty Acids, Omega-3; Fish Oils; Thiamine

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders; Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Oils; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dr Dur E Shawar, PhD*

CONTACT

03348405894; shehwar88@gmail.com

Prof Dr Inayat Shah, PhD

CONTACT

03321431414; inayat.shah@kmu.edu.pk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to one of four parallel groups: (1) prebiotics plus probiotics, (2) omega-3 fatty acids plus vitamin B1, (3) combined supplementation, or (4) placebo. Participants will remain in their assigned group throughout the 12-week intervention period.

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 24, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 25, 2026
• Last Updated: June 24, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Data will become available beginning 6 months after publication of the primary study results and will remain available for 5 years thereafter.
• 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.

Locations

PA (1)