Allogeneic Adipose Tissue-derived Mesenchymal Stem Cells for the Induction of Remission in Ulcerative Colitis

Ulcerative Colitis Clinical Trial

— ALOASCU  

Official title:

A Phase I/IIa Clinical Trial to Evaluate Safety and Efficacy of Adipose Tissue-derived Mesenchymal Stem Cells (ASC) on Induction to Remission in Ulcerative Colitis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01914887
• Other study ID #: HLPDIG-2010-01
• Secondary ID: 2010-023798-20
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: July 18, 2013
• Last updated: July 31, 2013
• Start date: June 2013
• Est. completion date: December 2013

Study information

• Verified date: July 2013
• Source: Instituto de Investigación Hospital Universitario La Paz
• Contact: Maria Dolores Martin Arranz, MD
• Phone: +34 917277467
• Email: mmartinarranz[@]salud.madrid.org
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
• Study type: Interventional

Clinical Trial Summary

The aims of our study are to evaluate the feasibility and safety of endoscopic injection of adipose tissue-derived mesenchymal stem cells in human subjects with moderate active ulcerative colitis, assessing the absence of adverse events associated to the investigational drug, and to evaluate the efficacy of the treatment to induce remission of moderate active ulcerative colitis, by improvements in disease activity index, quality of life index, and endoscopic index.

Description:

Mesenchymal stem cells (MSC) may be a therapeutic option in diseases associated with severe inflammation or auto-immune diseases, due to their immunomodulatory and anti-inflammatory properties. A number of clinical trials are being conducted worldwide testing th efficacy of MSC, mainly isolated from bone marrow, for different conditions, such as Graft Versus host Disease, refractory Crohn's Disease, ischemic stroke, acute myocardial infarction, type I Diabetes Mellitus, or Chronic Obstructive Pulmonary Disease. Usually, the route of administration of the cells in these studies is intravenous. Local injection of MSC for fistulizing Crohn's Disease has proven efficacious. Endoscopy is a routinary technique for the evaluation of gastrointestinal and colonic conditions. The purpose of our study is to evaluate safety and efficacy of the intracolonic injection by using a colonoscope of allogeneic adipose tissue-derived MSC in patients with moderate active ulcerative colitis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 8
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients of either sex aged 18 years and older

• Signed informed consent

• Patients with ulcerative colitis diagnosed at least 6 months earlier in accordance with usual criteria

• Left-sided colitis with moderate activity defined by a modified Truelove-Witts score between 11 and 21, and with no response to 4 weeks of treatment with oral and/or topical 5-aminosalicylates

• Negative pregnancy test for women of childbearing potential (from menarche to menopause) using consistently and correctly highly effective (i.e. less than 1% failure rate per year) methods of birth control

Exclusion Criteria:

• Mental disability that impedes adequate understanding of the study and of the associated procedures

• Extensive colitis

• Patients with an impaired general state which requires, according to the investigator judgment, immediate treatment with corticosteroids and/or anti-Tumor Necrosis Factor (TNF) and/or surgery

• Patients that fulfill criteria of corticodependency and in ongoing treatment with corticosteroids

• Patients with previous colectomies

• Known history of alcohol or other addictive substances abuse

• History of malignant disease - Patients having participated in clinical trials with any investigational drug within 6 months prior to enrolment in this study

• Patients with known allergies to penicillin, gentamicin, aminoglycosides, human serum albumin (HSA), Dulbecco's modified Eagle medium (DMEM), or materials of bovine origin

• Pregnant or breastfeeding women

• Presence of severe concomitant diseases

• Patients with suspicion of Crohn?s enterocolitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated colitis, or microscopic colitis

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colitis
• Colitis, Ulcerative
• Ulcer
• Ulcerative Colitis

Intervention

Drug:
• Allogeneic adipose tissue-derived mesenchymal stem cells
The cells will be given in different sites within the affected colonic submucosa at a total dose of 60 million cells with the use of a colonoscope.

Locations

Country	Name	City	State
Spain	Hospital Universitario La Paz	Madrid

Sponsors (3)

Lead Sponsor	Collaborator
Instituto de Investigación Hospital Universitario La Paz	Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz, Ministry of Health, Spain

Country where clinical trial is conducted

Spain, 

References & Publications (3)

Duijvestein M, Vos AC, Roelofs H, Wildenberg ME, Wendrich BB, Verspaget HW, Kooy-Winkelaar EM, Koning F, Zwaginga JJ, Fidder HH, Verhaar AP, Fibbe WE, van den Brink GR, Hommes DW. Autologous bone marrow-derived mesenchymal stromal cell treatment for refractory luminal Crohn's disease: results of a phase I study. Gut. 2010 Dec;59(12):1662-9. doi: 10.1136/gut.2010.215152. Epub 2010 Oct 4. — View Citation

García-Gómez I, Elvira G, Zapata AG, Lamana ML, Ramírez M, Castro JG, Arranz MG, Vicente A, Bueren J, García-Olmo D. Mesenchymal stem cells: biological properties and clinical applications. Expert Opin Biol Ther. 2010 Oct;10(10):1453-68. doi: 10.1517/14712598.2010.519333. Review. — View Citation

van Deen WK, Oikonomopoulos A, Hommes DW. Stem cell therapy in inflammatory bowel disease: which, when and how? Curr Opin Gastroenterol. 2013 Jul;29(4):384-90. doi: 10.1097/MOG.0b013e328361f763. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety	Evaluation of the presence of any event that could be considered adverse event, especially if it can be attributed to the investigational drug. Physical exam, vital signs, and laboratory tests (hemogram, biochemistry, coagulation, and cytokines) will be performed at 0, 9-10 days, and 4, 8, and 12 weeks.	Up to 12 weeks	Yes
Secondary	Efficacy: Change from Baseline in Modified Truelove-Witts score	Remission will be considered if it descends below 11, and response if it diminishes at least 30%. Modified Truelove-Witts score will be evaluated at 0, 4, 8, and 12 weeks.	Up to 12 weeks	No
Secondary	Efficacy: Change from Baseline in Quality of Life index, Inflammatory Bowel Disease Questionnaire (IBDQ-32)	Response will be considered if it improves at least 30%. IBDQ-32 will be evaluated at 0, 4, 8, and 12 weeks.	Up to 12 weeks	No
Secondary	Efficacy: Change from baseline in Mayo endoscopic index.	Remission will be considered if reaches 0 points and response if the score diminishes. Endoscopy will be performed at 0 and 8 weeks.	8 weeks	No
Secondary	Change from Baseline in C Reactive Protein	C Reactive Protein will be evaluated at 0, 9-10 days, and 4, 8, 12 weeks.	Up to 12 weeks	No
Secondary	Change from Baseline in fecal calprotectin	Fecal calprotectin will be evaluated at 0, 4, 8, and 12 weeks.	Up to 12 weeks	No