Adipose Mesenchymal Stem Cells (AMSC) for Treatment of Ulcerative Colitis

Study Overview
=================
Brief Summary
-----------------
Ulcerative colitis is a form of inflammatory bowel disease characterized by diffuse inflammation of the colonic mucosa. It affects the rectum and extends proximally along a variable length of the colon. Ulcerative colitis is a chronic condition with a relapsing remitting course. Mesenchymal stem cells (MSCs) are a subset of adult stem cells residing in many tissues, including bone marrow (BM), adipose tissue, umbilical cord blood. Recent experimental findings have shown the ability of MSCs to home to damaged tissues and to produce paracrine factors with anti-inflammatory properties, potentially resulting in reduction of inflammation and functional recovery of the damaged tissues. The purpose of our study is to evaluate safety and efficacy of the intracolonic injection by using a colonoscope of allogeneic adipose MSCs in patients with moderate active ulcerative colitis.

Official Title
-----------------
A Phase I/II Randomized, Controlled, Clinical Trial for Assessment of the Safety and Efficacy of Allogeneic Adipose Mesenchymal Stem Cells in Moderate to Severe Ulcerative Colitis Patients

Conditions
-----------------
Ulcerative Colitis (UC)

Intervention / Treatment
-----------------
* Biological: Adipose-cord mesenchymal stromal cells (A-MSCs)
* Other: Conventional drugs


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, 18-65 years old Diagnosis of ulcerative colitis diagnosed at least 6 months earlier Moderate or severe activity defined by a Mayo score No serious infection, chronic diseases, diabetes and tuberculosis Unefficient by using 5-ASA, glucocorticoid or azathioprine Written informed consents were obtained from all subjects Capable of good communication with researchers and follow the entire test requirements Negative pregnancy test for women of childbearing potential (from menarche to menopause) Exclusion Criteria: Pregnant or breastfeeding women or cognitively impaired adults History of malignant disease Infectious colitis Patients with known allergies to culture medium Patients having participated in clinical trials with any investigational drug within 1 month prior to enrolment in this study Patients with suspicion of Crohn's enterocolitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated colitis, or microscopic colitis Patients with previous colectomy Positive to one or more of the infectious disease panel Treatment with surgery or biological treatment (infliximab or adamizumab) or Cyclosporine or tacrolimus or mycophenolate in the 8 weeks prior to inclusion in the study Presence of severe concomitant diseases Patients with clostridium difficult or cytomegalovirus infection

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>interventions: The MSCs of 5×10*7 will be given in different sites within colonic submucosa at a total 100 ml with the use of the colonoscope. Once every week，a total of two times. Conventional drug therapy (5-amino-salicylic acid or glucocorticoid) is used | Biological: Adipose-cord mesenchymal stromal cells (A-MSCs)<br>* A-MSCs 5 x 10 7 diluted on 100 mL of normal saline<br>Other: Conventional drugs<br>* 5-amino-salicylic acid or glucocorticoid<br>|
| Other: Control group<br>interventions:Conventional drug therapy (5-amino-salicylic acid or glucocorticoid) is used | Other: Conventional drugs<br>* 5-amino-salicylic acid or glucocorticoid<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Endoscopic Score (as Measured by Ulcerative Colitis Endoscopic Index of Severity) | Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is defined as Ulcerative Colitis Endoscopic Index of Severity, with higher scores indicating more severe disease | Baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in clinical response (CDAI points) | CDAI is defined as Clinical Disease Activity Index | Baseline, 8 weeks | 
| To evaluate the quality of life index, Short Inflammatory Bowel Disease Questionnaire (SIBDQ) | The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) is a health-related quality of life (HRQoL) tool measuring physical, social, and emotional status. It includes 10-item form of questions. Each question is scored on a Likert scale from 1 (worst) to 7 (best), scores from each item are summed to produce a total score, increased more than 3 scores were considered remission. | Baseline, 8 weeks | 
| Histologic Evaluation of Ulcerative Colitis | A 10 to 20 centimeter (cm) biopsy sample of inflamed mucosal tissue was taken from the worst affected area and scored using the Riley Index. The Riley Index is a histologic scoring system for the assessment of the activity and severity of ulcerative colitis, ranging from 0 to 24. It consists of 6 histologic features (acute inflammatory cell infiltrate, crypt abscesses, mucin depletion, surface epithelial integrity, chronic inflammatory cell infiltrate, and crypt architectural irregularities), all scored on a 4-point scale (higher scores indicate more severe disease). | Baseline, 8 weeks | 
| Immune response in ulcerative colitis. | A number of soluble mediators are detected, including proinflammatory cytokines (TNF, IFN-γ, IL-6.) and anti-inflammatory cytokines (IL-10, IL-4.). | Baseline, 1, 4, 8 weeks | 
| Incidence of Treatment Adverse. | An AE was any untoward medical occurrence in a participant | Baseline, 1, 4, 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ulcerative colitis (UC), mesenchymal stem cells(MSC)