Clinical trial NCT06853522: hucMSCs Exosomes for the Treatment of Active Ulcerative Colitis
Official title: A Randomized, Single-blind Clinical Study of Human Umbilical Cord Mesenchymal Stem Cell Exosomes for the Treatment of Moderate-to-severe Active Ulcerative Colitis After Existing Therapy Failure
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Ulcerative Colitis (UC)
Lead sponsor: Shanghai East Hospital
Sponsor class: OTHER
First posted: 2025-03-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and efficacy of hUC-MSCs-Exos in the treatment of ulcerative colitis.

Detailed description: A large number of previous studies and literature data collection have demonstrated the efficacy of hUC-MSCs-Exos in animal models of inflammatory bowel disease, so the investigators will further verify the safety and effectiveness of hUC-MSCs-Exos in the treatment of UC patients, and provide new ideas for clinical treatment of UC.

Eligibility criteria: Inclusion Criteria:

1. Subjects have had UC for at least 3 months (since symptom onset). The diagnosis should be confirmed by clinical and endoscopic evidence and confirmed by histopathological reports (note: if no previous reports are available, endoscopy and histopathology may be performed at the time of screening).
2. Subjects had active UC, defined as four-component Mayo score of 6-12 (inclusive), endoscopy score ≥2, rectal bleeding score ≥1, and bowel frequency score ≥1.
3. 18 to 75 years old, weight ≥40 kg
4. Meet at least one of the following a/b/c criteria: a. inadequate or non-response to one or more of the following treatments: i) oral prednisone ≥40mg/ day (or equivalent) or budesonide ≥9mg/ day or equivalent or beclomethasone ≥5mg/ day for at least 2 weeks. ii) At least 8 weeks of immunomodulators (AZA≥2 mg/kg/ day or 6-MP≥1.0mg/kg/ day \[or lower doses, but 6-thioguanine nucleotides with therapeutic concentrations recorded\]). iii) Oral administration of aminosalicylate (e.g. Mesalazine, salazine sulfopyridine, oxalazine, balsalazine) in accordance with the dosage and duration of the applicable local instructions. iv) The frontier therapy for UC has completed at least the induction dosing regimen, At doses greater than or equal to the approved instructions: anti-TNF anti-integrins (e.g., Vederizumab), JAK inhibitors (e.g., Tofaciib, Upatinib, or filgotinib), anti-IL-23 or anti-IL-12/23 drugs for the treatment of UC (e.g., ulinumab), S1PR modulators (e.g., ozamod) b. Corticosteroid dependence: failure to taper successfully to \<10mg/ day of prednisone or equivalent or \<6mg/ day of budesonide or \<5mg/ day of beclometasone within 3 months of starting treatment (i.e., disease onset), or relapse occurs within 3 months of stopping corticosteroids. c. Intolerance to 1 or 2 of the following treatments (e.g., inability to reach the therapeutic dose or duration of treatment due to dose-limiting adverse reactions) i) corticosteroids: Adverse reactions associated with dose-limiting therapy may include, but are not limited to, infections, hyperglycemia, osteoporosis, insomnia, or psychiatric disorders. ii) Immunomodulators: Adverse reactions associated with dose-restricted therapeutic administration may include, but are not limited to, infection, nausea/vomiting, fatigue, myelosuppression, or liver toxicity.
5. Being treated with any of the following permitted drugs during the study period and meeting the drug stabilization requirements (if applicable): a. Oral corticosteroids must be stable for at least 2 weeks before randomization at an equivalent dose of ≤20 mg prednisone or ≤9mg budesonide or ≤5mg beclomethasone per day. b. A steady dose of oral aminosalicylate should be maintained for at least 2 weeks before randomization. c.AZA, 6-MP, or MTX(≤15 mg/ week) should be maintained at a stable dose for at least 4 weeks before randomization.
6. Participate voluntarily and sign a written informed consent. -

Exclusion Criteria:

1. Diagnosis of CD or undefined colitis (IBD- undefined) or other types of colitis or enteritis that may confuse assessment of effectiveness.
2. The current diagnosis is explosive colitis and/or toxic megacolon.
3. Had received fecal microbial transplantation within 4 weeks prior to randomization.
4. Had been hospitalized for UC within 2 weeks prior to screening.
5. There is clear evidence of past or current low or high grade colon dysplasia, including dysplasia detected during screening colonoscopy that has not been completely resectable.
6. Have any active or severe infection that does not resolve after adequate treatment.
7. Hepatitis B, hepatitis C virus infection, tuberculosis, HIV, uncontrollable diabetes, mental illness.
8. Have undergone organ transplantation requiring sustained immunosuppressive therapy.
9. A history of cancer within the past 5 years (except for completely treated non-melanoma skin cell carcinoma or carcinoma in situ of the cervix after complete surgical removal). Subjects who have had a diagnostic evaluation that suggests malignancy (e.g., chest or breast imaging) and who cannot reasonably rule out malignancy after additional clinical evaluation will be excluded from this study.
10. A history of drug or alcohol abuse in the 6 months prior to screening (as reported by the subject).

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Primary outcomes:
measure: Mayo Score
timeFrame: Baseline, 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
Secondary outcomes:
measure: Geboes Score
timeFrame: Baseline, at 12 weeks after treatment.
measure: Inflammatory Bowel Disease Questionnaire (IBDQ)
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: The item of urgency to defecate
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: EQ-5D-5L
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: CRP (C - reactive protein)
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: fecal calprotectin
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: immune cell subsets
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: BMI (Body Mass Index)
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: albumin
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Hemoglobin
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: body temperature
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Respiratory Rate
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Blood Pressure
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Heart Rate
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Blood White Blood Cells
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Bloos Red Blood Cells
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Platelets
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Urine White Blood Cells
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Urine Red Blood Cells
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Urinary Protein
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: occult blood test (OB)
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: alanine aminotransferase (ALT)
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: aspartate aminotransferase (AST)
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: serum creatinine (Cr)
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
measure: Blood Urea Nitrogen (BUN)
timeFrame: Baseline, at 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
References: