Table 2.
Clinical trials in inflammatory bowel diseases
| No. | Start year | Cell source | Autologous/allogeneic | Administration route | Number of cells infused | Diseases | Number of patients | Follow-up period | Phase | Study design | ClinicalTrials.gov identifier | Status | Result | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2006 | Bone marrow | Allogeneic | Peripheral vein | 8 × 106 cells/kg, 2 times or 2 × 106 cells/kg, 2 times | Crohn’s disease | 10 | 4 weeks | Phase 2 | Randomized, parallel assignment, open label | NCT00294112 | Completed | ||
| 2 | 2007 | Bone marrow | Allogeneic | Peripheral vein | Total of 6 × 108 cells/patient, 4 times or total of 12 × 108 cells/patient, 4 times |
Crohn’s disease | 98 | 24 weeks | Phase 3 | Randomized, parallel assignment, double blind | NCT00543374 | Completed | ||
| 3 | 2010 | Adipose tissue | Autologous | Unknown | Unknown | Fistulizing Crohn’s disease | 15 | 3 years | Phase 1–2 | Non-randomized, single group assignment, open label | NCT01157650 | Completed | ||
| 4 | 2015 | Umbilical cord | Allogeneic | Peripheral vein | Unknown | Crohn’s disease | 32 | 1 year | Phase 1–2 | Randomized, parallel assignment, open label | NCT02445547 | Completed | ||
| 5 | 2012 | Bone marrow | Allogeneic | Peripheral vein | 2 × 108 cells/patient, more than 4 times | Crohn’s disease | 11 | 4 weeks | Phase 1–2 | Non-randomized, single group assignment, open label | NCT01510431 | Completed | ||
| 6 | 2010 | Bone marrow | Allogeneic | Peripheral vein | 2 × 106 cells/kg, 4 times | Crohn’s disease | 15 | 6 weeks | Phase 2 | Non-randomized, single group assignment, open label | NCT01090817 | Completed | Improvement in CDAI, AQoL score. Decrease in CRP. Endoscopic improvement | 24 |
| 7 | 2012 | Bone marrow | Autologous | Peripheral vein | 2 × 106 cells/kg, 5 × 106 cells/kg, or 1 × 107 cells/kg | Crohn’s disease | 16 | 1 year | Phase 1 | Non-randomized, single group assignment, open label | NCT01659762 | Completed | ||
| 8 | 2010 | Bone marrow | Allogeneic | Intralesional | 1 × 107 cells/patient, 3 × 107 cells/patient, or 9 × 107 cells/patient | Fistulizing Crohn’s disease | 21 | 12 weeks | Phase 1–2 | Randomized, parallel assignment, double blind | NCT01144962 | Completed | Local treatment with MSCs showed promotion of fistula healing. Lower MSC dose seemed superior. | 25 |
| 9 | 2009 | Adipose tissue | Autologous | Intralesional | 3 × 107 cells/patient (in the event of incomplete closure at 8 weeks, a second injection was given that contained 1.5 times more cells than the f irst) | Fistulizing Crohn’s disease | 43 | 8 weeks | Phase 1 | Non-randomized, single group assignment, open label | NCT00992485 | Completed | Local treatment with MSCs showed promotion of fistula healing. | 26 |
| 10 | 2010 | Adipose tissue | Allogeneic | Intralesional | 2 × 107 cells/patient (in the event of incomplete closure at 12 weeks, an additional 4 × 107 cells were administered) |
Fistulizing Crohn’s disease | 24 | 24 weeks | Phase 1–2 | Non-randomized, single group assignment, open label | NCT01372969 | Completed | Local treatment with MSCs showed promotion of fistula healing. | 27 |
| 11 | 2009 | Adipose tissue | Autologous | Intralesional | 1 × 107 cells/patient, 2 × 107 cells/patient, or 4 × 107 cells/patient |
Fistulizing Crohn’s disease | 10 | 4 weeks | Phase 1 | Non-randomized, single group assignment, open label | NCT00992485 | Completed | Local treatment with MSCs showed promotion of fistula healing. All patients with complete healing showed a sustained effect. | 28 |
| 12 | 2009 | Adipose tissue | Allogeneic | Intralesional | 2 × 107 cells/patient (in the event of incomplete closure at 12 weeks, an additional 4 × 107 cells were administered) | Fistulizing Crohn’s disease | 10 | 12 weeks | Phase 1–2 | Non-randomized, single group assignment, open label | NCT00999115 | Completed | Local treatment with MSCs showed promotion of fistula healing; 60% of patients achieved complete healing. | 29 |
| 13 | 2009 | Adipose tissue | Autologous | Intralesional | 1 × 107 cells/cm2 | Fistulizing Crohn’s disease | 43 | 8 weeks | Phase 2 | Non-randomized, single group assignment, open label | NCT01011244 | Completed | In most cases, complete closure after initial treatment was well-sustained over a 24-month period. | 30 |
| 14 | 2007 | Bone marrow | Allogeneic | Peripheral vein | Total of 6 × 108 cells/patient, 4 times or total of 1.2 × 109 cells/patient, 4 times | Crohn’s disease | 330 | 4 weeks | Phase 3 | Randomized, parallel assignment, double blind | NCT00482092 | Active | ||
| 15 | 2012 | Adipose tissue | Allogeneic | Intralesional | 1.2 × 108 cells/patient | Fistulizing Crohn’s disease | 212 | 24 weeks | Phase 3 | Randomized, parallel assignment, double blind | NCT01541579 | Active | Local treatment with MSCs showed promotion of fistula healing. | 31 |
| 16 | 2010 | Bone marrow | Allogeneic | Peripheral vein | 2 × 10^8 cells/patient, 3 times | Crohn’s disease | 120 | 180 days | Phase 3 | Non-randomized, single group assignment, open label | NCT01233960 | Active | ||
| 17 | 2015 | Adipose tissue | Autologous | Intralesional | Unknown | Fistulizing Crohn’s disease | 10 | 62 weeks | Phase 2 | Non-randomized, single group assignment, open label | NCT02403232 | Recruiting | ||
| 18 | 2013 | Bone marrow | Autologous | Intralesional | Unknown | Fistulizing Crohn’s disease | 10 | 16 weeks | Phase 1 | Randomized, parallel assignment, single blind | NCT01874015 | Recruiting | ||
| 19 | 2015 | Adipose tissue | Allogeneic | Peripheral vein | 5 × 107 cells/patient, 7.5 × 107 cells/patient, or 1 × 108 cells/patient | Crohn’s disease | 9 | 4 weeks | Phase 1 | Non-randomized, single group assignment, open label | NCT02580617 | Recruiting | ||
| 20 | 2013 | Umbilical cord | Allogeneic | Peripheral vein | 5 × 107 cells/patient or 1 × 108 cells/patient | Crohn’s disease | 24 | 12 weeks | Phase 1–2 | Non-randomized, single group assignment, open label | NCT02000362 | Recruiting | ||
| 21 | 2013 | Adipose tissue | Autologous | Intralesional | 2 × 107 cells/patient | Fistulizing Crohn’s disease | 20 | 2–24 months | Phase 1 | Non-randomized, single group assignment, open label | NCT01915927 | Recruiting | ||
| 22 | Unknown | Bone marrow | Autologous | Peripheral vein | 1–2 × 106 cells/kg | Crohn’s disease | 10 | 6 weeks | Phase 1 | Unknown | – | – | Three patients showed clinical response (decrease in CDAI).Three patients required surgery due to disease worsening. | 32 |
| 23 | 2016 | Bone marrow | Allogeneic | Intralesional | 2 × 107 cells/patient | Fistulizing Crohn’s disease | 20 | 7, 10, 16 months | Phase 1 | Non-randomized, single group assignment, open label | NCT02677350 | Not yet recruiting | ||
| 24 | 2015 | Umbilical cord | Allogeneic | Peripheral vein | 1 × 106 cells/kg, 3 times | Ulcerative colitis | 30 | 24 weeks | Phase 1–2 | Randomized, parallel assignment, single blind | NCT02442037 | Recruiting | ||
| 25 | 2015 | Adipose tissue | Allogeneic | Through a colonoscope | 6 × 107 cells/patient | Ulcerative colitis | 8 | 12 weeks | Phase 1–2 | Non-randomized, single group assignment, open label | NCT01914887 | Unknown | ||
| 26 | 2015 | Umbilical cord | Allogeneic | First: peripheral vein, second: superior mesenteric artery | First: 3.8 ± 1.6 × 107 cells/patient, second: 1.5 × 107 cells/patient | Ulcerative colitis | 80 | 12 weeks | Phase 1–2 | Non-randomized, single group assignment, open label | NCT01221428 | Unknown | Decrease in the median Mayo score and histology score. Improvement in IBDQ scores. | 33 |
CD Crohn’s disease, CDAI Crohn’s Disease Activity Index, AQoL The Assessment of Quality of Life, CRP C-reactive protein, IBDQ Inflammatory Bowel Disease Questionnaire