GenesiDol for the Management of Musculoskeletal Pain

Official title

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

Overview

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

• Other Genesidol
  administration of the supplement to patients with chronic inflammatory bowel diseases

Primary outcome measures

• Change from baseline in musculoskeletal pain intensity measured by Visual Analog Scale (VAS) at 8 weeks [Time frame: Baseline to 8 weeks]

Secondary outcome measures (12)

• Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain [Time frame: Up to 1 year]
• Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain [Time frame: Up to 1 year]
• Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain [Time frame: Up to 1 year]
• Psychological profile assessed by validated psychological questionnaires in adult IBD patients with musculoskeletal pain [Time frame: Up to 1 year]
• 1. Gut microbiota alpha diversity assessed by Shannon Diversity Index [Time frame: Up to 1 year]
• Gut microbiota beta diversity assessed by Bray-Curtis dissimilarity index [Time frame: Up to 1 year]
• Relative abundance of selected bacterial taxa in fecal samples [Time frame: Up to 1 year]
• Intestinal response in Crohn's disease assessed by Crohn's Disease Activity Index (CDAI) [Time frame: Up to 1 year]
• Intestinal response in Ulcerative Colitis assessed by Mayo Score [Time frame: 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) [Time frame: Baseline to 12 weeks after completion of supplementation]
• Change from baseline in serum zonulin levels at 12 weeks after completion of supplementation [Time frame: 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) [Time frame: Baseline to 20 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07447154 · ID: 8300

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗