Clinical trial NCT01914887: Allogeneic Adipose Tissue-derived Mesenchymal Stem Cells for the Induction of Remission in Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Ulcerative Colitis
Keywords: Ulcerative Colitis
Inflammatory Bowel Disease
Mesenchymal stem cells
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
Collaborators: name: Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
name: Ministry of Health, Spain
First posted: 2013-08-02
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety
timeFrame: Up to 12 weeks
Secondary outcomes:
measure: Efficacy: Change from Baseline in Modified Truelove-Witts score
timeFrame: Up to 12 weeks
measure: Efficacy: Change from Baseline in Quality of Life index, Inflammatory Bowel Disease Questionnaire (IBDQ-32)
timeFrame: Up to 12 weeks
measure: Efficacy: Change from baseline in Mayo endoscopic index.
timeFrame: 8 weeks
measure: Change from Baseline in C Reactive Protein
timeFrame: Up to 12 weeks
measure: Change from Baseline in fecal calprotectin
timeFrame: Up to 12 weeks
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
Study officials:
affiliation: Gastroenterology Department
name: Maria Dolores Martin Arranz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Garcia-Gomez I, Elvira G, Zapata AG, Lamana ML, Ramirez M, Castro JG, Arranz MG, Vicente A, Bueren J, Garcia-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.
citation: 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.
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.