hucMSCs Exosomes for the Treatment of Active Ulcerative Colitis

Early Phase 1Not Yet RecruitingNCT06853522

Shanghai East Hospital40 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Ulcerative Colitis (UC)

Interventions

exosomes derived from human umbilical cord mesenchymal stem cellsDRUG

The corresponding exosome content of 60×10\^6 umbilical cord mesenchymal stem cells was given

saline +5% albuminDRUG

Equal amount of saline +5% albumin was given

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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). \-

Locations (1)

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

Outcomes

Primary Outcomes

Mayo Score

The complete Mayo Score consists of four assessments, each scored on a scale of 0 to 3: stool frequency, rectal bleeding, endoscopy, and the physician's global assessment (PGA) of disease activity. The endoscopy subscore of the complete Mayo Score is derived from the central reading of endoscopy results by a qualified central laboratory. Patient-reported stool frequency and rectal bleeding, as well as the PGA reported by the clinician, will be collected in an electronic diary.

Time frame: Baseline, 1 week, 4 weeks, 8 weeks, and 12 weeks after treatment.

Secondary Outcomes

Geboes Score

It is the most commonly used histological scoring system for colonic mucosa in the field of ulcerative colitis (UC). It is divided into six grades: 1) Structural changes (Grade 0); 2) Chronic inflammatory infiltration (Grade 1); 3) Neutrophils and eosinophils in the lamina propria (Grade 2); 4) Neutrophils in the epithelium (Grade 3); 5) Crypt destruction (Grade 4); 6) Erosion or ulceration (Grade 5). Each grade is further divided into four subcategories. The Geboes score ranges from 0 to 5.4, with higher scores indicating more severe inflammation. Typically, active histological inflammation in UC is defined as a Geboes score of ≥2B.1.

Time frame: Baseline, at 12 weeks after treatment.

Inflammatory Bowel Disease Questionnaire (IBDQ)

The IBDQ is a well-established assessment tool for measuring disease-specific health-related quality of life. It consists of 32 items : bowel symptoms (10 items), systemic symptoms (5 items), emotional functioning (12 items), and social functioning (5 items). The questionnaire is scored using a 7-point Likert scale, ranging from worst health (1) to best health (7). Domain scores are calculated by summing the item responses, with higher values indicating better quality of life.The total score range of the IBDQ is 32-224, which can be obtained by adding up the scores of individual domains. According to the total score, a meaningful change in the IBDQ score (also defined as an IBDQ response) is defined as a change of ≥ 16 points, and this threshold has been applied in studies involving subjects with Crohn's disease (CD) or ulcerative colitis (UC). In addition, IBDQ remission can be defined as a total score of ≥ 170 points.

Central Contacts

Lan Zhong

CONTACT

13162099450 lanzhong@tongji.edu.cn

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.