Allogeneic Adipose Tissue-derived Mesenchymal Stem Cells for the Induction of Remission in Ulcerative Colitis (ALOASCU)
Primary Purpose
Ulcerative Colitis
Status
Unknown status
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
Allogeneic adipose tissue-derived mesenchymal stem cells
Sponsored by
About this trial
This is an interventional treatment trial for Ulcerative Colitis focused on measuring Ulcerative Colitis, Inflammatory Bowel Disease, Mesenchymal stem cells
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
Sites / Locations
- Hospital Universitario La PazRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
allogeneic ASCs
Arm Description
Treatment consists in a cell suspension (5 million cells/mL) in aseptic buffered solution containing human expanded adipose-derived stem cells (eASCs) of allogeneic origin in disposable vials with no preservative agents. 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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
Change from Baseline in C Reactive Protein
C Reactive Protein will be evaluated at 0, 9-10 days, and 4, 8, 12 weeks.
Change from Baseline in fecal calprotectin
Fecal calprotectin will be evaluated at 0, 4, 8, and 12 weeks.
Full Information
NCT ID
NCT01914887
First Posted
July 18, 2013
Last Updated
July 31, 2013
Sponsor
Instituto de Investigación Hospital Universitario La Paz
Collaborators
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz, Ministry of Health, Spain
1. Study Identification
Unique Protocol Identification Number
NCT01914887
Brief Title
Allogeneic Adipose Tissue-derived Mesenchymal Stem Cells for the Induction of Remission in Ulcerative Colitis
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Unknown status
Study Start Date
June 2013 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
December 2013 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto de Investigación Hospital Universitario La Paz
Collaborators
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz, Ministry of Health, Spain
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis
Keywords
Ulcerative Colitis, Inflammatory Bowel Disease, Mesenchymal stem cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
allogeneic ASCs
Arm Type
Experimental
Arm Description
Treatment consists in a cell suspension (5 million cells/mL) in aseptic buffered solution containing human expanded adipose-derived stem cells (eASCs) of allogeneic origin in disposable vials with no preservative agents. 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.
Intervention Type
Drug
Intervention Name(s)
Allogeneic adipose tissue-derived mesenchymal stem cells
Other Intervention Name(s)
Cx-601 (company code)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety
Description
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.
Time Frame
Up to 12 weeks
Secondary Outcome Measure Information:
Title
Efficacy: Change from Baseline in Modified Truelove-Witts score
Description
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.
Time Frame
Up to 12 weeks
Title
Efficacy: Change from Baseline in Quality of Life index, Inflammatory Bowel Disease Questionnaire (IBDQ-32)
Description
Response will be considered if it improves at least 30%. IBDQ-32 will be evaluated at 0, 4, 8, and 12 weeks.
Time Frame
Up to 12 weeks
Title
Efficacy: Change from baseline in Mayo endoscopic index.
Description
Remission will be considered if reaches 0 points and response if the score diminishes. Endoscopy will be performed at 0 and 8 weeks.
Time Frame
8 weeks
Title
Change from Baseline in C Reactive Protein
Description
C Reactive Protein will be evaluated at 0, 9-10 days, and 4, 8, 12 weeks.
Time Frame
Up to 12 weeks
Title
Change from Baseline in fecal calprotectin
Description
Fecal calprotectin will be evaluated at 0, 4, 8, and 12 weeks.
Time Frame
Up to 12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maria Dolores Martin Arranz, MD
Phone
+34 917277467
Email
mmartinarranz@salud.madrid.org
First Name & Middle Initial & Last Name or Official Title & Degree
Fernando de Miguel, PhD
Phone
+34 917277389
Email
fernando.demiguel@salud.madrid.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria Dolores Martin Arranz, MD
Organizational Affiliation
Gastroenterology Department
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital Universitario La Paz
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Dolores Martin Arranz, MD
Phone
+34 917277467
Email
mmartinarranz@salud.madrid.org
First Name & Middle Initial & Last Name & Degree
Fernando de Miguel, PhD
Phone
+34 917277389
Email
fernando.demiguel@salud.madrid.org
First Name & Middle Initial & Last Name & Degree
Maria Dolores Martin Arranz, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
20831449
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.
Results Reference
background
PubMed Identifier
20921206
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.
Results Reference
background
PubMed Identifier
23666365
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.
Results Reference
background
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Allogeneic Adipose Tissue-derived Mesenchymal Stem Cells for the Induction of Remission in Ulcerative Colitis
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