Radar degli Studi Clinici

Imidazole Propionate (ImP)

Plasma ImP concentration: Primary metabolite produced by histidine-metabolizing gut bacteria, strongly associated with insulin resistance and type 2 diabetes risk Change from baseline: Reduction in ImP levels indicating improved metabolic health

Baseline to week 4

Gut Microbiome Composition

Gut microbiome composition and functional capacity will be assessed from stool samples using 16S rRNA gene sequencing and metagenomic sequencing. Analyses will evaluate overall microbial community structure, relative abundance of histidine-metabolising bacteria, and functional pathways related to imidazole propionate production. Measurement details: Analytical method: 16S rRNA gene sequencing and shotgun metagenomic sequencing Units: Relative abundance (%), diversity indices (unitless), and pathway abundance (relative abundance)

Baseline to week 4

Histidine Metabolic Pathway - Histidine

Histidine: Precursor amino acid for ImP synthesis. Plasma histidine concentration will be quantified as a marker of substrate availability within the histidine metabolic pathway.

Baseline to week 4

Histidine Metabolic Pathway - Histamine

Histamine: Alternative histidine metabolite. Plasma histamine concentration will be measured as an alternative downstream metabolite of histidine metabolism.

Baseline to week 4

Histidine Metabolic Pathway - Urocanic acid

Urocanic acid: Intermediate metabolite in histidine degradation pathway. Plasma urocanic acid concentration (µmol/L), an intermediate metabolite in the histidine degradation pathway, will be quantified.

Baseline to week 4

Insulin Sensitivity and Metabolic Health: HOMA-IR

Insulin sensitivity and beta-cell function will be assessed using the Homeostatic Model Assessment (HOMA). Indices will be calculated from fasting plasma glucose and fasting serum insulin concentrations. Specific indices derived: * HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) HOMA indices derived using the HOMA2 model calculator (Oxford Centre for Diabetes, Endocrinology and Metabolism

Baseline to week 4

Insulin Sensitivity and Metabolic Health: HOMA2

Insulin sensitivity and beta-cell function will be assessed using the Homeostatic Model Assessment (HOMA). Indices will be calculated from fasting plasma glucose and fasting serum insulin concentrations. Specific indices derived: * HOMA2-%B (beta-cell function) using the HOMA2 calculator HOMA indices derived using the HOMA2 model calculator (Oxford Centre for Diabetes, Endocrinology and Metabolism

Baseline to week 4

Safety and Tolerability - Adverse events

Adverse events: Any untoward medical occurrences during the study period

Baseline to week 4

Safety and Tolerability - Blood pressure

Safety and tolerability, vital signs - blood pressure

Baseline to week 4

Safety and Tolerability - Heart Rate

Safety and tolerability, vital signs - heart rate

Baseline to week 4

Safety and Tolerability - E/LFT (electrolytes)

Safety and tolerability biomarkers - Electrolytes Tests. These analytes form part of a single standard clinical chemistry panel (E/LFT) performed as one laboratory assessment for safety monitoring rather than independent mechanistic endpoints. A comprehensive clinical chemistry panel will be used to assess E/LFTs. The panel will be performed as a single laboratory assessment using standard automated clinical chemistry methods in an accredited pathology laboratory.

Baseline to week 4

Safety and Tolerability - E/LFT (Liver Function test)

Safety and tolerability biomarkers - Liver Function Tests. These analytes form part of a single standard clinical chemistry panel (E/LFT) performed as one laboratory assessment for safety monitoring rather than independent mechanistic endpoints. A comprehensive clinical chemistry panel will be used to assess E/LFTs. The panel will be performed as a single laboratory assessment using standard automated clinical chemistry methods in an accredited pathology laboratory.

Baseline to week 4