GenesiDol for the Management of Musculoskeletal Pain (Genesis-Joint)

GenesiDol for the Management of Musculoskeletal Pain in Patients With Inflammatory Bowel Disease

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammatory Bowel Diseases
• Intervention / Treatment: Other: Genesidol

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Franco Scaldaferri; Phone Number: +390630156265; Email: franco.scaldaferri@policlinicogemelli.it
• Study Contact Backup: Name: Francesca Profeta; Phone Number: +390630157104; Email: francesca.profeta@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gensidol; administration of the supplement to patients with chronic inflammatory bowel diseases	Other: Genesidol; administration of the supplement to patients with chronic inflammatory bowel diseases
Placebo Comparator: placebo; administration of the placebo to patients with chronic inflammatory bowel diseases	Other: Genesidol; administration of the supplement to patients with chronic inflammatory bowel diseases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in musculoskeletal pain intensity measured by Visual Analog Scale (VAS) at 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).	Baseline to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain	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).	Up to 1 year
Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain	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).	Up to 1 year
Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain	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).	Up to 1 year
Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain	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.	Up to 1 year
1. Gut microbiota alpha diversity assessed by Shannon Diversity Index	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).	Up to 1 year
Gut microbiota beta diversity assessed by Bray-Curtis dissimilarity index	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.	Up to 1 year
Relative abundance of selected bacterial taxa in fecal 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.	Up to 1 year
Intestinal response in Crohn's disease assessed by Crohn's Disease Activity Index (CDAI)	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.	Up to 1 year
Intestinal response in Ulcerative Colitis assessed by Mayo Score	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).	Up to 1 year
Change from baseline in musculoskeletal pain intensity at 12 weeks after completion of supplementation measured by the Visual Analog Scale (VAS)	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).	Baseline to 12 weeks after completion of supplementation
Change from baseline in serum zonulin levels at 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).	Baseline to 12 weeks after completion of supplementation
Change from baseline in musculoskeletal pain intensity at 20 weeks in the control group measured by the Visual Analog Scale (VAS)	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).	Baseline to 20 weeks
Anxiety assessed by the Hospital Anxiety and Depression Scale - Anxiety Subscale	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).	Baseline to up to 1 year
Depression assessed by the Hospital Anxiety and Depression Scale - Depression Subscale	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).	Baseline to up to 1 year
Perceived stress assessed by the Perceived Stress Scale (10-item version)	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).	Baseline to up to 1 year
Pain coping strategies assessed by the Coping Strategies Questionnaire	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.	Baseline to up to 1 year
Change from baseline in psychological status assessed by validated questionnaires	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.	Baseline to up to 1 year
Change from baseline in nutritional status assessed by anthropometric and nutritional measures	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.	Baseline to up to 1 year
Change from baseline in gut microbiota composition assessed by stool sample analysis	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.	Baseline to up to 1 year
Change from baseline in metabolomic profile assessed by biological sample analysis	Change from baseline in metabolomic profile assessed by analysis of biological samples using validated metabolomic techniques in adult patients with inflammatory bowel disease.	Baseline to up to 1 year
Change from baseline in serum lipopolysaccharide (LPS) levels	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.	Baseline to up to 1 year
Change from baseline in serum zonulin levels	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.	Baseline to up to 1 year
Adherence to study product regimen assessed by weekly patient diaries	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.	Up to 1 year

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Franco Scaldaferri, Fondazione Policlinico Universitario A. Gemelli, IRCCS

Study record dates

Study Major Dates

• Study Start (Estimated): February 26, 2026
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): January 15, 2027

Study Registration Dates

• First Submitted: December 22, 2025
• First Submitted That Met QC Criteria: February 26, 2026
• First Posted (Actual): March 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Inflammatory Bowel Diseases
• Other Study ID Numbers: ID: 8300

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No