Dose-escalating Therapeutic Study of Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Fistulas in Patients With Refractory Perianal Crohn's Disease

NCT01144962 | Completed Phase 1 DMC

• 1 other identifier: P10.102
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

In a dose escalation study we will determine the safety and preliminary efficacy of allogeneic bone marrow mesenchymal stem cells (bmMSCs) in the induction of response for active fistulizing Crohn's Disease (CD).

Conditions

Crohn's Disease; Fistula

Keywords

Crohn's Disease; Fistula; Mesenchymal Stem Cell; Mesenchymal Stromal Cell; MSC; IBD

Outcome Measures

Primary Outcomes (1)

• Safety and efficacy (fistula closure)

  i) the number of adverse and serious adverse events and ii) a reduction in the number of draining fistulas, which is defined as absence of discharge and absence of collections of ≥2 cm directly related to the treated fistulas tracts as measured by MRI (Magnetic Resonance Imaging).

  12 weeks

Secondary Outcomes (5)

• Clinical scores

  12 weeks

• Endoscopic scores

  12 weeks

• Quality of life

  12 weeks

• C-reactive protein (CRP)

  12 weeks

• Safety

  12 and 24 weeks

Study Arms (4)

Control group

SHAM COMPARATOR

Patients in the control group will undergo surgical localization, curettage of the fistulous tract and closure of the internal opening, without injection of MSCs.

Procedure: Localization, curettage of the fistulous tract and closure of the internal opening without MSC injection.

Cohort 1

ACTIVE COMPARATOR

10x10\^6 MSC

Procedure: Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection.

Cohort 2

ACTIVE COMPARATOR

30x10\^6 MSC

Procedure: Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection.

Cohort 3

ACTIVE COMPARATOR

90x10\^6 MSC

Procedure: Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection.

Interventions

Localization, curettage of the fistulous tract and closure of the internal opening without MSC injection. PROCEDURE

Patients will undergo surgical localization, curettage of the fistulous tract and closure of the internal opening, without injection of MSCs.

Control group

Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection. PROCEDURE

Patients will undergo surgical localization, curettage of the fistulous tract and closure of the internal opening, with local injection of indicated dose of MSCs

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women \> 18 years of age
• Patient must have had CD (for at least 3 months from the time of initial diagnosis). The diagnosis of CD must have been confirmed by endoscopic and histologic evidence
• CDAI score of \<250 at screening and baseline
• Peri-anal fistulas must be refractory to conventional medical therapy Which means that at some time during the course of the disease, patient must have received both steroids and immunosuppressive agents (for example, azathioprine, 6-mercaptopurine (6-MP), methotrexate, or infliximab) which did not result in an adequate response to treatment
• Patients included in the study might be receiving 5-aminosalicylic acid (5-ASA), steroids, azathioprine, 6-MP, methotrexate, or any similar drug at the time of enrolment and is allowed to have a history of infliximab treatment, provided the following conditions are fulfilled at screening:
• The dose of 5-ASA (both oral and rectal) must have been stable for at least 4 weeks prior to enrollment
• The dose of steroids must be stable for at least 4 weeks prior to enrollment
• The dose of immunosuppressants (for example azathioprine, 6-MP, or methotrexate) must have been stable for at least 8 weeks prior to enrollment and the patient on therapy for at least three months prior to enrollment
• The last dose of infliximab or other anti-TNF drug is \> 8 weeks prior to enrollment
• No need for immediate surgery (obstruction, strictures or abscess)
• If female and of child-bearing age, patient must be non-pregnant non-breastfeeding, and use adequate contraception
• Patient is willing to participate in the study and has signed the informed consent. Consent must be obtained prior to any study procedure

You may not qualify if:

• Patients with evidence of acute peri-anal infection, presence of peri-anal abscesses larger than 2 cm, and anal or rectal stricture
• Patients with evidence of any infections needing antibiotic treatment
• Rectovaginal fistulas, or complex peri-anal fistulas with more than two internal openings
• Patients suffering from renal- or hepatic failure
• Use of any investigational drug within 1 month prior to screening or within 5 half-lives of the investigational agent, whichever is longer
• Patient is allergic to gadolinium (MRI contrast agent)
• Patient with severe renal insufficiency defined as patients with a glomerular filtration rate (GFR) below 60 mL/min/1.73 m2. GFR = 186.3 x (serum creatinine)-1.154 x (age in years)-0.203 x 1.212 (if patient is black) x 0.742 (if female)
• Due to the high strength electromagnetic fields that will be used during MRI there is a risk of interference with any metallic implants in the body. The following conditions will disqualify patients from having an MRI and will be excluded from this study:
• Electronically, magnetically, and mechanically activated implants
• Ferromagnetic or electronically operated stapedial implants
• Cardiac pacemakers/carotid sinus pacemaker implant
• Hemostatic clips
• Metallic splinters in the orbit
• Insulin pumps and nerve stimulators
• Lead wires or similar wires

Sponsors & Collaborators

• Leiden University Medical Center: lead
• DigestScience: collaborator

Study Sites (1)

Leiden University Medical Center (LUMC)

Leiden, South Holland, 2333 ZA, Netherlands

Location

Related Publications (1)

• Molendijk I, Bonsing BA, Roelofs H, Peeters KC, Wasser MN, Dijkstra G, van der Woude CJ, Duijvestein M, Veenendaal RA, Zwaginga JJ, Verspaget HW, Fibbe WE, van der Meulen-de Jong AE, Hommes DW. Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Promote Healing of Refractory Perianal Fistulas in Patients With Crohn's Disease. Gastroenterology. 2015 Oct;149(4):918-27.e6. doi: 10.1053/j.gastro.2015.06.014. Epub 2015 Jun 25.

  PMID: 26116801 DERIVED

MeSH Terms

Conditions

Crohn Disease; Fistula

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Hein W Verspaget, PhD

  Leiden University Medical Center (LUMC)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 14, 2010
• First Posted: June 16, 2010
• Study Start: June 1, 2010
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: December 30, 2014

Record last verified: 2014-12

Locations

NL (1)