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

Overview

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.

Full Title of Study: “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”

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Double (Participant, Outcomes Assessor)
• Study Primary Completion Date: June 1, 2021

Interventions

• Biological: Adipose-cord mesenchymal stromal cells (A-MSCs)
  • A-MSCs 5 x 10~7 diluted on 100 mL of normal saline
• Other: Conventional drugs
  • 5-amino-salicylic acid or glucocorticoid

Arms, Groups and Cohorts

• Experimental: Intervention group
  • 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
• Other: Control group
  • interventions:Conventional drug therapy (5-amino-salicylic acid or glucocorticoid) is used

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

• Change from Baseline in clinical response (CDAI points)
  • Time Frame: Baseline, 8 weeks
  • CDAI is defined as Clinical Disease Activity Index
• To evaluate the quality of life index, Short Inflammatory Bowel Disease Questionnaire (SIBDQ)
  • Time Frame: Baseline, 8 weeks
  • 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.
• Histologic Evaluation of Ulcerative Colitis
  • Time Frame: Baseline, 8 weeks
  • 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).
• Immune response in ulcerative colitis.
  • Time Frame: Baseline, 1, 4, 8 weeks
  • A number of soluble mediators are detected, including proinflammatory cytokines (TNF, IFN-γ, IL-6.) and anti-inflammatory cytokines (IL-10, IL-4.).
• Incidence of Treatment Adverse.
  • Time Frame: Baseline, 1, 4, 8 weeks
  • An AE was any untoward medical occurrence in a participant

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Liaocheng People’s Hospital
• Provider of Information About this Clinical Study
  • Principal Investigator: peng yan, Chief of gastroenterology – Liaocheng People’s Hospital
• Overall Official(s)
  • Peng Yan, MD, Study Chair, Liaocheng People’s Hospital
• Overall Contact(s)
  • Shaoda Ren, Ph.D., 86-0635-8272202, zslrsd@163.com