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Crohn's DiseasePhase 1/2NCT01144962

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

A Phase 1/2 study testing Localization, curettage of the fistulous tract and closure of the internal opening without MSC injection. and Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection. in people with Crohn's Disease and Fistula, run by Leiden University Medical Center at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Crohn's Disease, Fistula
What is being tested?
Localization, curettage of the fistulous tract and closure of the internal opening without MSC injection. and Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection.
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
1 siteNetherlands
Study dates
Jun 2010to Dec 2014
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 with previous surgical attempts to eradicate perianal fistulas are eligible for inclusion as are patients with setons in situ. Setons will be removed during the surgical procedure
  • 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:
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  • 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

Who cannot join

  • 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)
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  • 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
  • Metal intrauterine device
  • Change in concomitant medication:
  • Steroids must be stable for at least 4 weeks prior to enrollment
  • 5-ASA should be on a stable dose > 4 weeks prior to enrollment
  • Immunosuppressants (e.g. azathioprine, 6MP or methotrexate) should be on a stable dose > 8 weeks prior to enrolment
  • Infliximab or other anti-TNF antibody therapy should not be administered < 8 weeks prior to enrollment
  • Claustrophobia
  • Documented HIV (Human Immunodeficiency Virus) infection. Active hepatitis B, hepatitis C or TB
  • Patients who currently have or who have had an opportunistic infection (e.g., herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening
  • Serious infections (such as pneumonia or pyelonephritis) in the previous 3 months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator
  • Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence)
  • History of lymphoproliferative disease including lymphoma
  • Patient is unwilling or unable to comply with the study procedures

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Leiden University Medical Center (LUMC)

    Leiden, South Holland, 2333 ZA

Other trials in Netherlands

About this study

Official title: Allogeneic Bone Marrow Derived Mesenchymal Stem Cells for the Treatment of Fistulas in Patients With Refractory Perianal Crohn's Disease

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).

Read the detailed description

Despite the introduction of anti-TNFa (tumor necrosis factor alpha) therapy, perianal disease still accounts for a high rate of morbidity in patients diagnosed with CD. Recently, a phase II multicenter randomized study was reported showing that expanded adipose tissue derived mesenchymal stem cells (atMSCs) in combination with fibrin glue was an effective and safe treatment for complex perianal fistula. However, dose escalation of allogeneic bone marrow (bm) MSCs for the local treatment of perianal fistulas has not been studied.

In this study, three escalating doses will be tested in a total of three cohorts. MSC implantation will be preceded by surgical localization, curettage of the fistulous tract and closure of the internal opening. Per cohort, patients will be randomized in a 5:2 fashion to receive either 10x10^6 (cohort 1), 30x10^6 (cohort 2) or 90x10^6 (cohort 3) bmMSCs or no cells (control group).

The primary endpoint will be assessed at week 12: 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.

Being tested
Localization, curettage of the fistulous tract and closure of the internal opening without MSC injection., Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection.
Keywords
Crohn's Disease, Fistula, Mesenchymal Stem Cell, Mesenchymal Stromal Cell, MSC, IBD
Medical subject headings
Crohn Disease, Fistula

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

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

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

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

Study groups in NCT01144962
Study groupRoleWhat they receive
Control groupSham comparatorPatients in the control group will undergo surgical localization, curettage of the fistulous tract and closure of the internal opening, without injection of MSCs.
Receives: Procedure: Localization, curettage of the fistulous tract and closure of the internal opening without MSC injection.
Cohort 1Active comparator10x10^6 MSC
Receives: Procedure: Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection.
Cohort 2Active comparator30x10^6 MSC
Receives: Procedure: Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection.
Cohort 3Active comparator90x10^6 MSC
Receives: Procedure: Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and efficacy (fistula closure)

    1. 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).

    Measured: 12 weeks

Secondary outcomes (5)

  1. Clinical scores

    1. To assess changes in the Crohn's Disease Activity Index (CDAI), the Perianal Disease Activity Index (PDAI) and the adapted Vaizey fecal incontinence score before and after mesenchymal stem cell (MSC) treatment;

    Measured: 12 weeks

  2. Endoscopic scores

    1. To compare endoscopic changes before and after local bmMSC treatment using the Crohn's Disease Endoscopic Index of Severity (CDEIS) and simplified endoscopic activity score for Crohn's disease (SES-CD);

    Measured: 12 weeks

  3. Quality of life

    1. To evaluate the effect of local treatment with autologous bmMSCs on the quality of life of patients with fistulizing CD using the short Inflammatory Bowel Disease Questionnaire (sIBDQ) and Short Form (SF)-36 score;

    Measured: 12 weeks

  4. C-reactive protein (CRP)

    1. To summarize the changes from baseline compared to 12 weeks in serum C-reactive protein (CRP).

    Measured: 12 weeks

  5. Safety

    1. To assess the incidence of surgical intervention and infections.

    Measured: 12 and 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionSep 2014
  4. Study completionDec 2014

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01144962
Sponsor's protocol ID
P10.102
Status last verified
Dec 2014
First submitted
14 Jun 2010
Last updated
30 Dec 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 26116801

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Localization, curettage of the fistulous tract and closure of the internal opening without MSC injection. and Localization, curettage of the fistulous tract and closure of the internal opening with local MSC injection. in people with Crohn's Disease and Fistula, run by Leiden University Medical Center at 1 site in Netherlands.

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 13 inclusion and 28 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: finished, as of the sponsor's last update on 30 Dec 2014. 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 Netherlands. 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. Some participants in this study may receive a placebo. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Safety and efficacy (fistula closure) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01144962, which also lists 1 linked publication.

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 30 Dec 2014.

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