Crohn's DiseasePhase 1/2NCT01540292
Mesenchymal Stem Cell Therapy for the Treatment of Severe or Refractory Inflammatory and/or Autoimmune Disorders
A Phase 1/2 study testing Mesenchymal Stem Cells (MSC) in people with Crohn's Disease, run by University of Liege at 1 site in Belgium.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Mesenchymal Stem Cells (MSC)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Feb 2013to 31 Dec 2015
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
- 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.
- 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).
- 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.
- Conditions
- Crohn's Disease
- Being tested
- Mesenchymal Stem Cells (MSC)
- Keywords
- Crohn's disease, Mesenchymal Stem Cell, Cell therapy, Allogeneic, Inflammatory disorders, Autoimmune disorders
- Medical subject headings
- Crohn Disease, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal Stem Cells (MSC)Biological
MSC (1.5-2 cells/kg BW) IV injection, twice at 4 weeks apart
| Study group | Role | What they receive |
|---|---|---|
| MSC | Experimental | 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. Receives: Biological: Mesenchymal Stem Cells (MSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response Rate
To assess clinical response rate defined by a 100 points decrease in Crohn's Disease Activity Index.
Measured: at week 8
Secondary outcomes (7)
Clinical Response
Measured: at week 2, 4, 8 and 12.
Remission
Remission, defined by Crohn's Disease Activity Index <150
Measured: at week 2, 4, 8 and 12.
Crohn's Disease Activity Index Level
Measured: at week 2, 4, 8 and 12.
C-reactive Protein levels
C-reactive Protein measured in blood.
Measured: at week 2, 4, 8 and 12.
Fecal calprotectin levels
Fecal calprotectin measured in stool samples
Measured: at week 2, 4, 8 and 12.
Immune modulation investigation
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).
Measured: at week 12.
Incidence of infections
Measured: by week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2012 (estimated)
- Study start1 Feb 2013
- Primary completion31 Dec 2015
- Study completion31 Dec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Liege
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yves Beguin, University of Liege
- Investigators
- Yves Beguin, MD, PhD, Study chair, CHU-ULgEdouard Louis, MD, PhD, Principal investigator, CHU-ULg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01540292
- Sponsor's protocol ID
- TJT1123
- Status last verified
- May 2021
- First submitted
- 22 Feb 2012
- Last updated
- 12 May 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mesenchymal Stem Cell Therapy for the Treatment of Severe or Refractory Inflammatory and/or Autoimmune Disorders
- ClinicalTrials.gov ID
- NCT01540292
- Acronym / sponsor ID
- TJT1123
- Conditions
- Crohn's Disease
- Keywords
- Crohn's disease, Mesenchymal Stem Cell, Cell therapy, Allogeneic, Inflammatory disorders, Autoimmune disorders
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of LiegeUniversity, hospital or other
- Study start
- 1 Feb 2013 (actual)
- Primary completion
- 31 Dec 2015 (actual)
- Study completion
- 31 Dec 2015 (actual)
- First posted
- 28 Feb 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- 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.
- 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).
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MSC | Experimental | Biological: Mesenchymal Stem Cells (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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mesenchymal Stem Cells (MSC)MSC (1.5-2 cells/kg BW) IV injection, twice at 4 weeks apart | Biological | MSC |
Primary outcome
Clinical Response Rate
Time frame: at week 8
To assess clinical response rate defined by a 100 points decrease in Crohn's Disease Activity Index.
7 secondary outcomes
Clinical Response
Time frame: at week 2, 4, 8 and 12.
Remission
Time frame: at week 2, 4, 8 and 12.
Crohn's Disease Activity Index Level
Time frame: at week 2, 4, 8 and 12.
C-reactive Protein levels
Time frame: at week 2, 4, 8 and 12.
Fecal calprotectin levels
Time frame: at week 2, 4, 8 and 12.
Immune modulation investigation
Time frame: at week 12.
Incidence of infections
Time frame: by week 12
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yves Beguin, MD, PhD study chair
CHU-ULg
Edouard Louis, MD, PhD principal investigator
CHU-ULg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mesenchymal Stem Cells (MSC) in people with Crohn's Disease, run by University of Liege at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Response Rate (time frame: at week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2021.