Ulcerative Colitis (UC)
Conditions
Keywords
Fucoidan, Gastrointestinal microbiome, Ulcerative, Colitis, Turbinaria, Phaeophyta, Sulfated polysaccharides
Brief summary
What is the research question being addressed? Does combining Turbinaria ornata-derived fucoidan with standard therapy lead to a significantly higher rate of gut health restoration-defined by increased fecal short-chain fatty acid (butyrate/acetate) levels, reduced fecal calprotectin, and improved stool consistency-compared to standard therapy alone in Ulcerative Colitis patients? Type of study: Interventional Study design: Randomized controlled trial Masking: Participants Control: Placebo Assignment: Parallel Purpose: Other Adjuvant / Add-On Therapy (Complementary Prebiotic Strategy) Study Phase: Phase1
Detailed description
Intervention Efficacy & Evidence Status Whether combining Turbinaria ornata-derived fucoidan with standard therapy leads to a statistically significant increase in gut health restoration in human Ulcerative Colitis (UC) patients remains an unproven hypothesis, as robust Phase II/III clinical trial data in humans is currently lacking. Preclinical animal models (such as DSS-induced colitis in mice) and in vitro fermentation models support the biological rationale for this combination: Fecal Short-Chain Fatty Acids (SCFAs): Marine sulfated polysaccharides (fucoidans) act as prebiotic non-digestible carbohydrates. Commensal anaerobic gut bacteria ferment fucoidan, leading to an increase in butyrate, acetate, and propionate levels. Fecal Calprotectin: Fucoidan suppresses the NF-κB and MAPK signaling pathways, decreasing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), reducing mucosal neutrophil infiltration, and subsequently lowering fecal calprotectin. Stool Consistency: Through structural restoration of epithelial tight junctions (ZO-1, Claudin-1) and mucin protection (MUC2), fucoidan mitigates mucosal erosion and diarrhea, improving stool consistency scores. Classification of the Intervention Intervention Category: Adjuvant / Add-On Therapy (Complementary Prebiotic Strategy) Sub-type: Natural Product-derived Bioactive / Marine Polysaccharide Supplement Mechanistic Role: Co-administered with standard pharmacotherapy (e.g., 5-aminosalicylates like Mesalamine, corticosteroids, or biologics) to target mucosal healing and gut dysbiosis concurrently with immune suppression. Phase IIa (Proof-of-Concept) is the most appropriate trial classification for testing Turbinaria ornata-derived fucoidan in Ulcerative Colitis (UC). Because oral fucoidan preparations have a recognized history of human use for other indications (such as osteoarthritis, oncological adjuncts, and metabolic health), its basic systemic safety and human oral tolerance are already documented. However, because it has never been evaluated in human UC populations. Primary Reasons for Phase IIa RecommendationEvaluating Disease-Specific Mucosal Safety: Ulcerative Colitis involves an inflamed, ulcerated, and hyper-permeable mucosal barrier. Even though fucoidan is safe in intact human guts, its local tolerance, systemic absorption rates, and safety profile must be confirmed specifically in patients with active mucosal friability. Determining Biological Proof-of-Concept: Phase IIa focuses on demonstrating that the drug hits its intended targets using surrogate biomarkers. Measuring fecal calprotectin reduction and changes in fecal SCFA (butyrate/acetate) levels provides objective evidence that the bioactive agent is exerting its anti-inflammatory and prebiotic effects in human UC. Preliminary Efficacy Signals: A Phase IIa design allows to observe preliminary clinical signal (stool consistency via the Bristol Stool Chart / Partial Mayo Score) before investing in large-scale multicenter Phase IIb/III randomized controlled trials.
Interventions
DIETARY_SUPPLEMENTLow molecular weight fucoidan and standard care
LMWF + 5-ASA Arm Oral administration of 85% purified, dehydrogenated low-molecular-weight fucoidan (\<40 kDa) at a weight-based dose (35 mg/kg/day for active flare) as an adjuvant to standard-of-care 5-aminosalicylate therapy.
placebo and 5 Aminosalicylic acid
Sponsors
Allama Iqbal Medical College
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Intervention model description
Intervention(s) planned: Arm Name: Active : Marine Polysaccharide Supplement(Low Molecular Weight Fucoidan capsules )+ 5-ASA Arm Oral administration of 85% purified, dehydrogenated low-molecular-weight fucoidan (\<40 kDa) at a weight-based dose (35 mg/kg/day for active flare) as an adjuvant to standard-of-care 5-aminosalicylate therapy. Arm Name: Control Placebo + 5-ASA Identical matching placebo capsule manufactured to mirror the active Low-Molecular-Weight Fucoidan (LMWF) extract capsule in size, shape, color, weight, texture, and odor as 1 capsule three times daily with meals + conventional Ulcerative Colitis therapy using 5-aminosalycilates.
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Male and female patients aged between 18-64 years; * Active mild to moderate diagnosed cases of uc * Voluntarily agreeing to participate and providing informed consent. *
Exclusion criteria
* Other autoimmune disorders and chronic diseases. * Patient with Clotting problems. * Patients using oral/intravenous steroids, leukotriene antagonists, immunosuppressant's, systemic photo chemotherapy, immunotherapy, allergen-specific immunotherapy, or Chinese herbal medicine within one month before enrolment. * Patient unable to take the trial supplements as scheduled or cooperate in filling out the questionnaire and taking a blood test. * Patients with a history of allergy * Patients suffering from serious infection requiring hospitalization assessed by a clinician * Severe organ dysfunction (e.g., heart failure, liver failure, liver cirrhosis, or renal failure assessed by a clinician. * Pregnant women or those preparing for pregnancy, and those in lactation. * Patient with hypothyroidism. * Patients with a history of allergy to Soy. * Acute severe (fulminant) UC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in intestinal inflammation | [baseline and week 12] | 1.Change in intestinal inflammation measured through Quantitative ELISA assay of fecal calprotectin. Mean difference in fecal calprotectin concentration between the Turbinaria ornata fucoidan + standard therapy group and the placebo + standard therapy group, evaluated for a statistically significant reduction toward mucosal healing. \[baseline and wk 12\] |
Countries
Pakistan
Contacts
PRINCIPAL_INVESTIGATORRozina Shahadat Khan, MBBS, M.PHIL,MSPH, CHPE,PHDHND
Saglik Bilimleri Universitesi
Outcome results
None listed