Inflammatory Bowel Diseases
Conditions
Brief summary
Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are chronic, relapsing conditions characterized by persistent inflammation of the gastrointestinal tract and a significant impact on patients' quality of life. Crohn's disease can involve any part of the gastrointestinal tract, most commonly the terminal ileum and colon, whereas ulcerative colitis is confined to the colonic mucosa. Typical symptoms include abdominal pain, diarrhea, fatigue, fever, and weight loss, often alternating between periods of remission and disease flare-ups.In addition to intestinal involvement, IBD are frequently associated with extraintestinal manifestations affecting multiple organ systems. Among these, enteropathic arthritis represents one of the most common and clinically relevant complications. It belongs to the spectrum of spondyloarthritis, a group of inflammatory joint disorders characterized by axial and/or peripheral involvement, enthesitis, and dactylitis. Enteropathic arthritis is reported in a substantial proportion of IBD patients and may occur independently of intestinal disease activity. Although its pathogenesis is not fully understood, current evidence suggests a multifactorial mechanism involving gut microbiota dysbiosis, immune dysregulation with expansion of Th17 cells, and migration of activated immune cells to the joints in genetically predisposed individuals.Management of musculoskeletal manifestations in IBD remains challenging. Conventional therapeutic strategies are primarily aimed at controlling intestinal inflammation and often fail to adequately address joint pain. Escalation of immunomodulatory or biologic therapies may be required when articular symptoms parallel intestinal flares; however, persistent pain can occur even during disease remission, potentially due to nociplastic or neuropathic mechanisms or degenerative joint disease. The long-term use of analgesic and anti-inflammatory medications, including COX-2 inhibitors, antidepressants, anticonvulsants, opioids, and cannabis, is associated with relevant adverse effects and may worsen gastrointestinal symptoms.Given these limitations, non-pharmacological and complementary approaches are gaining interest. Nutraceutical interventions have shown promising results in alleviating musculoskeletal symptoms while minimizing gastrointestinal toxicity. GenesiDol, a nutrigenomic dietary supplement containing palmitoylethanolamide, avocado/soy extracts, probiotics, antioxidants, and neuroprotective compounds, represents a potential supportive strategy for the management of chronic musculoskeletal pain in patients with IBD.
Interventions
OTHERGenesidol
administration of the supplement to patients with chronic inflammatory bowel diseases
Sponsors
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged between 18 and 65 years. * Patients diagnosed with IBD for at least six months. * Ability to understand and provide signed informed consent. * Patients with IBD and a prior diagnosis of axial/peripheral spondyloarthritis without objec-tive evidence of joint inflammation (clinical and/or instrumental, as per rheumatological as-sessment), but with persistent musculoskeletal pain (VAS scale score \>50/100 in the last week; HAQ-DI score \>0.5; FACIT Fatigue Scale score ≥40; NPS score \>1) Or * Patients with IBD and musculoskeletal pain who do not meet the criteria for the diagnosis of spondyloarthritis or other inflammatory arthritis (as per rheumatological assessment), but with persistent musculoskeletal pain (VAS scale score \>5/10 in the last week; HAQ-DI score \>0.5; FACIT Fatigue Scale score ≥40; NPS score \>1).
Exclusion criteria
* Patients under 18 or over 65 years of age. * Patients affected by Inflammatory Bowel Disease-Unclassified (IBD-U). * Inability to provide informed consent. * Refusal to provide informed consent. * Presence of severe language deficits. * Patients diagnosed with axial/peripheral spondyloarthritis with objective evidence of joint inflammation (clinical and/or instrumental, as per rheumatological assessment). * Patients with other comorbidities that may invalidate rheumatological evaluation (Substance Use Disorder, Schizophrenia Spectrum and other Psychotic Disorders, Diabetes Mellitus, other rheumatological diseases). * Patients on anticoagulant and/or antiepileptic therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in musculoskeletal pain intensity measured by Visual Analog Scale (VAS) at 8 weeks | Baseline to 8 weeks | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain | Up to 1 year | 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). |
| 1. Gut microbiota alpha diversity assessed by Shannon Diversity Index | Up to 1 year | 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). |
| Gut microbiota beta diversity assessed by Bray-Curtis dissimilarity index | Up to 1 year | 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 selected bacterial taxa in fecal samples | Up to 1 year | 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 in Crohn's disease assessed by Crohn's Disease Activity Index (CDAI) | Up to 1 year | 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 in Ulcerative Colitis assessed by Mayo Score | Up to 1 year | 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 musculoskeletal pain intensity at 12 weeks after completion of supplementation measured by the Visual Analog Scale (VAS) | Baseline to 12 weeks after completion of supplementation | 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 at 12 weeks after completion of supplementation | Baseline to 12 weeks after completion of supplementation | 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 musculoskeletal pain intensity at 20 weeks in the control group measured by the Visual Analog Scale (VAS) | Baseline to 20 weeks | 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 assessed by the Hospital Anxiety and Depression Scale - Anxiety Subscale | Baseline to up to 1 year | 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 assessed by the Hospital Anxiety and Depression Scale - Depression Subscale | Baseline to up to 1 year | 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 assessed by the Perceived Stress Scale (10-item version) | Baseline to up to 1 year | 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 assessed by the Coping Strategies Questionnaire | Baseline to up to 1 year | 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 by validated questionnaires | Baseline to up to 1 year | 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 by anthropometric and nutritional measures | Baseline to up to 1 year | 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 | Baseline to up to 1 year | 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 biological sample analysis | Baseline to up to 1 year | 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 | Baseline to up to 1 year | 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 | Baseline to up to 1 year | 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 study product regimen assessed by weekly patient diaries | Up to 1 year | 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. |
Contacts
CONTACTFranco Scaldaferri
CONTACTFrancesca Profeta
PRINCIPAL_INVESTIGATORFranco Scaldaferri
Fondazione Policlinico Universitario A. Gemelli, IRCCS
Outcome results
None listed