Mesenchymal Stem Cell Therapy for the Treatment of Severe or Refractory Inflammatory and/or Autoimmune Disorders

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University Hospital of Liege
Sponsor:
Information provided by (Responsible Party):
Yves Beguin, University Hospital of Liege
ClinicalTrials.gov Identifier:
NCT01540292
First received: February 22, 2012
Last updated: January 17, 2013
Last verified: January 2013
  Purpose

This project aims to assess safety and efficacy of allogeneic Mesenchymal stem Cell (MSC) in Crohn's disease refractory or intolerant to conventional therapies. Twenty patients with active refractory Crohn's disease defined by a Crohn's Disease Activity Index (CDAI) > 220 despite conventional treatment will be included over 4 years in this phase I-II trial. This will be a pilot open label trial. Patients will be treated with 2 successive injections of allogeneic MSC at baseline and 4 weeks later. Patients will be followed up at weeks 2, 4, 8 and 12.


Condition Intervention Phase
Crohn's Disease
Biological: Mesenchymal Stem Cells (MSC)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Mesenchymal Stem Cell Therapy for the Treatment of Severe or Refractory Inflammatory and/or Autoimmune Disorders

Resource links provided by NLM:


Further study details as provided by University Hospital of Liege:

Primary Outcome Measures:
  • Clinical Response Rate [ Time Frame: at week 8 ] [ Designated as safety issue: No ]
    To assess clinical response rate defined by a 100 points decrease in Crohn's Disease Activity Index.


Secondary Outcome Measures:
  • Clinical Response [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
  • Remission [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
    Remission, defined by Crohn's Disease Activity Index <150

  • Crohn's Disease Activity Index Level [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
  • C-reactive Protein levels [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
    C-reactive Protein measured in blood.

  • Fecal calprotectin levels [ Time Frame: at week 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
    Fecal calprotectin measured in stool samples

  • Immune modulation investigation [ Time Frame: at week 12. ] [ Designated as safety issue: No ]

    The following parameters will be taken in account.

    • Nucleated cell count and differential on an automated cell counter;
    • FACS analysis with determination of the % cells (on total WBC) with the markers :

      • CD3+, CD4+, CD8+, CD19+, CD45RA+, CD45RO+, CD56+
      • CD3+CD4+, CD3+CD8+; CD3+CD56+;
      • CD4+CD45RA+, CD4+CD45RO+;
      • CD3-CD56+.
    • Regulatory T-cell (Treg) levels;
    • Immunoglobulin levels (baseline and week 12);
    • Vβ repertoire of T lymphocytes (baseline and week 12);
    • TRECs quantification in T lymphocytes (baseline and week 12).

  • Incidence of infections [ Time Frame: by week 12 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: March 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSC
Patients with Crohn's disease (refractory or intolerant to conventional therapies) treated with 2 successive injections of 1.5-2.0 x 10E6 allogenic MSC/kg BW at baseline and 4 weeks later.
Biological: Mesenchymal Stem Cells (MSC)
MSC (1.5-2 cells/kg BW) IV injection, twice at 4 weeks apart

Detailed Description:
  1. Collection and expansion of MSC Bone marrow collection and MSC expansion cultures will be carried out at the Laboratory of Cell and Gene Therapy (LTCG) at the University of Liège. Bone marrow (50 ml) will be collected from unrelated donors under local anesthesia, mononuclear cells will be isolated, and cultured for a total of about 4 weeks. After a sufficient number of passages, the cells will be harvested, washed and frozen.
  2. MSC injections MSC will be thawed and diluted at the Laboratory of Cell and Gene Therapy (LTCG), transported to the hospital ward and injected intravenously within 1 hour of thawing through a central catheter (when available) or a good peripheral vein. A dose of 1.5 - 2.0 x 106/kg recipient MSC should be ideally administered at each infusion. MSC will be infused even if the number of post-thaw cells is lower than that. Patients with Crohn's disease will receive two injections of allogenic MSC 4 weeks apart (week 0 and 4).
  3. Patients Follow up

3.1. Quality controls of MSC products Quality controls of MSC product will include microscopy, nucleated cell count and differential, cell viability testing, microbiology testing (including standard virology, bacterial culture and detection of mycoplasmal enzymes by bioluminescence, endotoxin testing, karyotype and FACS analysis (cells must be positive for :CD90 > 70%,CD105 > 70 %,CD73 > 70 %; and negative for :CD14 < 5%,CD34 < 5%, CD45 < 5%, CD3 < 1%).

3.2. Toxicities of cell infusions: Potential toxicities associated with MSC infusions will be carefully monitored per the institution's standards and documented on the infusion report and/or the SAE report form. No dosage modifications are scheduled. In case of severe reaction to the first MSC infusion, the second infusion will not be performed.

3.3. Clinical data The following parameters will be followed at baseline as well as at week 2, 4, 8 and 12 : CDAI level, CRP levels, fecal calprotectin levels. In addition, duration of hospitalization, infections, any other serious complication, and eath and survival will be recorded.

3.4. Immunologic data: Immune function in the patient will be monitored at baseline and appropriate intervals: nucleated cell count and differential; FACS analysis with determination of the % cells (on total WBC) with the markers :CD3+, CD4+, CD8+, CD19+, CD45RA+, CD45RO+, CD56+, CD3+CD4+, CD3+CD8+; CD3+CD56+; CD4+CD45RA+, CD4+CD45RO+; CD3-CD56+; regulatory T-cell (Treg) levels; immunoglobulin levels, Vβ repertoire of T lymphocytes; TRECs quantification in T lymphocytes.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 and 75 years old
  • Crohn's disease affecting terminal ileum, colon or both with diagnosis confirmed according to Lennard Jones criteria
  • Clinically active disease with a CDAI between 220 and 450 and biologically active disease with a CRP > 5 mg/l and/or fecal calprotectin > 150 microg/g
  • Resistance or intolerance to mesalazine, steroids, purine analogues, methotrexate, infliximab and adalimumab
  • Adequate venous access (central catheter or good peripheral veins)
  • Willingness to sign the informed consent and enter the clinical trial

Exclusion Criteria:

  • Any condition not fulfilling inclusion criteria
  • Indication for surgery
  • Symptomatic stricture
  • Undrained perianal or intraabdominal abscess
  • Change in mesalazine dosage within the last 4 weeks, change in steroid dosage within the last two weeks, change in immunosuppressant dosage within the last 3 months, use of anti-TNF treatment within the last two months
  • HIV positive
  • Uncontrolled infection, arrhythmia or hypertension
  • Terminal organ failure:

    • Renal: anuria, serious fluid overload, GFR < 30 ml/min, dialysis;
    • Pulmonary: DLCO < 35% and/or receiving supplementary continuous oxygen;
    • Hepatic: Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease;
    • Cardiac: Symptomatic coronary artery disease or other cardiac failure requiring therapy; ejection fraction < 35%; uncontrolled arrhythmia, uncontrolled hypertension
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01540292

Contacts
Contact: Yves Beguin, MD, PhD +32/4/3667201 yves.beguin@chu.ulg.ac.be
Contact: Edouard Louis, MD, PhD +32/4/3667256 edouard.louis@ulg.ac.be

Locations
Belgium
University Hospital Liège Recruiting
Liège, Belgium, 4000
Sponsors and Collaborators
University Hospital of Liege
Investigators
Study Chair: Yves Beguin, MD, PhD CHU-ULg
Principal Investigator: Edouard Louis, MD, PhD CHU-ULg
  More Information

No publications provided

Responsible Party: Yves Beguin, Professor, University Hospital of Liege
ClinicalTrials.gov Identifier: NCT01540292     History of Changes
Other Study ID Numbers: TJT1123
Study First Received: February 22, 2012
Last Updated: January 17, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital of Liege:
Crohn's disease
Mesenchymal Stem Cell
Cell therapy
Allogeneic
Inflammatory disorders
Autoimmune disorders

Additional relevant MeSH terms:
Crohn Disease
Autoimmune Diseases
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014