GenesiDol for the Management of Musculoskeletal Pain

Change from baseline in perceived musculoskeletal pain intensity, measured using the Visual Analog Scale (VAS), a 100-mm visual analog scale with a minimum score of 0 mm (no pain) and a maximum score of 100 mm (worst imaginable pain). Higher scores indicate greater pain intensity (worse outcome).

Anxiety assessed by the Hospital Anxiety and Depression Scale - Anxiety Subscale (HADS-A) Psychological profile - anxiety will be assessed using the Hospital Anxiety and Depression Scale - Anxiety Subscale, a 7-item questionnaire with a total score ranging from 0 to 21. Higher scores indicate greater anxiety severity (worse outcome).

Depression assessed by the Hospital Anxiety and Depression Scale - Depression Subscale (HADS-D).Psychological profile - depression will be assessed using the Hospital Anxiety and Depression Scale - Depression Subscale, a 7-item questionnaire with a total score ranging from 0 to 21. Higher scores indicate greater depression severity (worse outcome).

Perceived stress assessed by the Perceived Stress Scale (PSS-10). Psychological profile - stress will be assessed using the Perceived Stress Scale (10-item version), with total scores ranging from 0 to 40. Higher scores indicate higher perceived stress (worse outcome).

Pain coping strategies assessed by the Coping Strategies Questionnaire (CSQ). Psychological profile - pain coping strategies will be assessed using the Coping Strategies Questionnaire, with subscale scores varying depending on the coping domain. Higher scores indicate greater use of the specific coping strategy; interpretation (adaptive vs maladaptive) depends on the subscale.

Gut microbiota alpha diversity will be assessed from fecal samples using the Shannon Diversity Index, a quantitative measure of within-sample microbial diversity. The index has no fixed upper limit; higher values indicate greater microbial diversity (generally considered a more favorable outcome).

Between-sample microbial diversity will be assessed using the Bray-Curtis dissimilarity index, which ranges from 0 to 1. Higher values indicate greater dissimilarity in microbial composition between samples.

Relative abundance of pre-specified bacterial taxa will be assessed from fecal samples and expressed as percentage (%) of total bacterial sequences. Values range from 0% to 100%. Higher percentages indicate greater relative abundance of the specific taxon analyzed.

Intestinal response to therapy in participants with Crohn's disease will be assessed using the Crohn's Disease Activity Index (CDAI). The CDAI score typically ranges from 0 to approximately 600, with higher scores indicating more severe disease activity (worse outcome). Clinical response will be defined according to established criteria (e.g., reduction of ≥100 points from baseline), and remission as CDAI <150.

Intestinal response to therapy in participants with ulcerative colitis will be assessed using the Mayo Score, which ranges from 0 to 12. Higher scores indicate more severe disease activity (worse outcome). Clinical response and remission will be defined according to established criteria (e.g., total score ≤2 with no individual subscore >1 for remission).

Change from baseline in perceived musculoskeletal pain intensity measured using the Visual Analog Scale (VAS), a 100-mm visual analog scale ranging from 0 mm (no pain) to 100 mm (worst imaginable pain). Higher scores indicate greater pain intensity (worse outcome).

Assessments will be performed at baseline and 12 weeks after completion of the GenesiDol dietary supplementation protocol in adult patients with inflammatory bowel disease (IBD).

Change from baseline in serum zonulin levels measured in ng/mL in adult patients with inflammatory bowel disease (IBD). There is no universally established fixed minimum or maximum value; typical reference values in serum are approximately 34 ng/mL in healthy individuals. Higher levels are generally interpreted as reflecting increased intestinal permeability (worse outcome).

Change from baseline in perceived musculoskeletal pain intensity in the control group (participants who did not receive the dietary supplementation protocol), measured using the Visual Analog Scale (VAS), a 100-mm visual analog scale ranging from 0 mm (no pain) to 100 mm (worst imaginable pain). Higher scores indicate greater pain intensity (worse outcome).

Anxiety will be assessed using the Hospital Anxiety and Depression Scale - Anxiety Subscale, a 7-item questionnaire with total scores ranging from 0 to 21. Higher scores indicate greater anxiety severity (worse outcome).

Depression will be assessed using the Hospital Anxiety and Depression Scale - Depression Subscale, a 7-item questionnaire with total scores ranging from 0 to 21. Higher scores indicate greater depression severity (worse outcome).

Perceived stress will be assessed using the Perceived Stress Scale (10-item version), with total scores ranging from 0 to 40. Higher scores indicate higher perceived stress levels (worse outcome).

Pain coping strategies will be assessed using the Coping Strategies Questionnaire, which includes multiple subscales. Subscale scores vary depending on the coping domain assessed. Higher scores indicate greater use of the specific coping strategy; interpretation as adaptive or maladaptive depends on the subscale.

Change from baseline in psychological status assessed using validated questionnaires measuring anxiety, depression, stress, and pain-related psychological factors in adult patients with inflammatory bowel disease.

Change from baseline in nutritional status assessed using anthropometric measures and nutritional assessment tools (e.g., body mass index, body composition, dietary assessment) in adult patients with inflammatory bowel disease.

Change from baseline in gut microbiota composition assessed by stool sample analysis, including microbial diversity indices and relative abundance of bacterial taxa, in adult patients with inflammatory bowel disease.

Change from baseline in metabolomic profile assessed by analysis of biological samples using validated metabolomic techniques in adult patients with inflammatory bowel disease.

Change from baseline in serum lipopolysaccharide (LPS) levels, measured as a biomarker of intestinal permeability, to assess the effect of GenesiDol on epithelial barrier function.

Change from baseline in serum zonulin levels, measured as a biomarker of intestinal epithelial barrier function, to assess the effect of GenesiDol on intestinal permeability.

Adherence to the study product regimen will be measured using weekly patient diaries in which participants record daily intake of the study product. Data will be collected for both the active treatment group and the placebo group, and adherence will be summarized as the proportion of prescribed doses taken over the study period.