A Clinical Trial Evaluating Fecal Microbiota Transplantation (FMT) in Adolescents With ADHD

Feasibility: Number of Participants Enrolled

Feasibility of FMT in an Adolescent Population With ADHD will be determined by: Successful enrollment of at least 45 participants across the four trial arms

Feasibility: Number of Participants Completing Study Protocol

Feasibility of FMT in an Adolescent Population With ADHD will be determined by: A minimum of 45 participants to complete study until the 24-week primary endpoint

Feasibility: Number of Prescribed Capsule Doses Successfully Ingested

Feasibility of FMT in an Adolescent Population With ADHD will be determined by adherence to study protocols: Receive at least 10/20 capsules per dosing visit

Feasibility: Number of Participants Completing Required Study Visits

Feasibility of FMT in an Adolescent Population With ADHD will be determined by the adherence to study protocols: Attend all visits - attend the baseline visit (Visit 2- V2) and at least 2 follow up visits (V4-10).

Stool Samples - Microbiome Composition - Metagenomics: Change From Baseline in Gut Microbiome Alpha Diversity (Shannon Diversity Index) and Beta Diversity (Bray-Curtis Dissimilarity) via Shotgun Metagenomic Sequencing

The effect of FMT on microbiome composition will be assessed through changes from baseline (V2) to post-intervention follow-up (V4-10). Evaluated using shotgun metagenomic sequencing of stool samples analyzed via the MetaPhlAn4 bioinformatics pipeline. Species-level relative abundances are used to calculate the Shannon Diversity Index (alpha diversity) and Bray-Curtis dissimilarity (beta diversity) at each study visit. Higher Shannon values indicate greater microbial community diversity and species richness, while Bray-Curtis dissimilarity measures compositional differences between samples over time. Samples are collected at 5 time points.

Stool Samples - Microbiome Functional Activity - Metabolomics: Change From Baseline in Fecal Metabolite Concentrations Measured via Proton Nuclear Magnetic Resonance (1H-NMR) Spectroscopy

The effect of FMT on microbiome functional activity will be assessed through changes in the following from baseline (V2) to post-intervention follow-up (V4-10): Evaluated by quantifying fecal metabolite concentrations from stool samples using a 500 MHz 1H-NMR spectrometer and Chenomx NMR Suite library profiling. Individual target metabolites (e.g., short-chain fatty acids) are quantified across study visits. Samples are collected at 5 time points.

Saliva Samples - Oral Microbiome Composition - Metagenomics: Change From Baseline in Oral Microbiome Alpha Diversity (Shannon Diversity Index) and Beta Diversity (Bray-Curtis Dissimilarity) via Shotgun Metagenomic Sequencing

The effect of FMT on oral microbiome composition will be assessed through changes from baseline (V2) to post-intervention follow-up (V4-10). Evaluated using shotgun metagenomic sequencing of saliva samples analyzed via the MetaPhlAn4 bioinformatics pipeline. Species-level relative abundances are used to calculate the Shannon Diversity Index (alpha diversity) and Bray-Curtis dissimilarity (beta diversity) at each study visit. Higher Shannon values indicate greater oral microbial community diversity and species richness, while Bray-Curtis dissimilarity measures compositional differences between samples over time. Samples are collected at 5 time points.

Saliva Samples - Oral Microbiome Composition - Metabolomic Analysis: Change From Baseline in Salivary Metabolite Concentrations Measured via Proton Nuclear Magnetic Resonance (1H-NMR) Spectroscopy

To assess the effect of FMT on the oral microbiome through changes in the following from baseline (V2) to post intervention follow up (V4-10): Evaluates functional metabolic changes in saliva by quantifying individual metabolite concentrations using 1H-NMR spectroscopy collected at 5 time points.

ADHD Symptomology: Change From Baseline in the Swanson, Nolan, and Pelham Parent Rating Scale IV (SNAP-IV 26) Total Score

Evaluate the effectiveness of adjunct oral FMT with treatment as usual (TAU) ± antibiotics versus TAU ± antibiotics alone in managing ADHD symptoms. This is assessed via changes from baseline to post-intervention follow-up (Weeks 4-24) using the parent-administered Swanson, Nolan, and Pelham Parent Rating Scale IV (SNAP-IV 26). Items are scored 0-3 across a total score range of 0-78, where higher scores indicate greater symptom severity.

Functional Impairment: Change From Baseline in the Weiss Functional Impairment Rating Scale Self-Report (WFIRS-S) and Parent-Report (WFIRS-P) Total Score

Evaluate the effectiveness of adjunct oral FMT with treatment as usual (TAU) ± antibiotics versus TAU ± antibiotics alone in managing functional impairment. This is assessed via changes from baseline to post-intervention follow-up (Weeks 4-24) using the Weiss Functional Impairment Rating Scale Self-Report (WFIRS-S) and Parent-Report (WFIRS-P). Items are scored 0-3, where higher total and domain scores indicate greater functional impairment

Anxiety and Depression: Change From Baseline in the Revised Children's Anxiety and Depression Scale Self-Report (RCADS) and Parent Version (RCADS-P) Total Score

Evaluate the effectiveness of adjunct oral FMT with treatment as usual (TAU) ± antibiotics versus TAU ± antibiotics alone in managing anxiety and depression. This is assessed via changes from baseline to post-intervention follow-up (Weeks 4-24) using the Revised Children's Anxiety and Depression Scale Self-Report (RCADS) and Parent Version (RCADS-P). Individual item scores (0-3) are converted to T-scores, where higher scores indicate greater symptom severity.