Complex perianal Crohn's disease
Conditions
Interventions
None listed
Sponsors
Amsterdam UMC loc AMC
Eligibility
Inclusion criteria
Inclusion criteria: All patients in treatment groups: 1. Confirmed diagnosis of CD with previously or currently documented luminal inflammation (endoscopy and histopathology) 2. Complex perianal fistula, defined as either involving the upper two-third of the sphincter complex (i.e., high intersphincteric, high transsphincteric, suprasphincteric or extrasphincteric course of the fistula tract), having multiple external openings, are associated with pain or fluctuation suggesting a perianal abscess or are associated with a rectovaginal fistula or anorectal stricture or active rectal ulcers, with active drainage (fluid loss on gentle compression; perianal fistulas that were previously close but that reopened can be included). 3. Age 16 or older 4. Signed informed consent Mesenchymal stem cell patients: 5. Failure of conventional fistula treatment (anti-TNF and at least one surgical closure) Hyperbaric oxygen patients: 6. Failure of conventional fistula treatment (anti-TNF) Patients with cryptoglandular fistulas without CD: • Active cryptoglandular fistula, either superficial or complex • No previous documentation of CD activity and a fecal calprotectin 5mm (endoscopy and histopathology) • Age 16 y/o or older • No previous use of immunomodulators or biologicals Patients with CD without proctitis and without perianal CD: • Confirmed diagnosis of CD with previously documented luminal inflammation (endoscopy and histopathology), no earlier documentation of rectal ulcerations >5mm • Age 16 y/o or older • No previous use of immunomodulators or biologicals
Exclusion criteria
Exclusion criteria: 1. Patients with Ulcerative Colitis or IBD-U 2. Presence of impassible anal stricture 3. Superficial fistula only 4. Rectovaginal fistulas 5. Patients with ongoing abdominal or undrained perianal abscesses after repeated examination-under-anesthesia with drainage by incision or seton placement 6. Patients with a seton in situ > 12 months 7. Patients with an ostomy 8. Enteric pathogens (such as Salmonella, Shigella, Yersinia, Campylobacter and C. difficile) detected by stool analysis within 2 weeks prior to enrollment or at screening 9. Active or planned pregnancy 10. Absolute contra-indications to perform MRI (e.g., claustrophobia), for relative contra-indications (e.g., metal implants) the MRI protocol could be adjusted upon decision with the treating physicians and patient 11. Contra-indication for endoscopy 12. Active participation in another interventional trial 13. Patients who received any investigational drug in the past 30 days or 5 half-lives, whichever is longer 14. Pregnancy and lactation 15. Patients with a history of colon cancer or colonic dysplasia, unless sporadic adenoma, which has been removed 16. A history of alcohol or illicit drug use that in the opinion of the principal investigator (PI) would interfere with study procedures 17. Patients with psychiatric problems that in the opinion of the PI would interfere with study procedures 18. Patients unable to attend all study visits 19. Patients with a history of non-compliance with clinical study protocols Anti-TNF patients 20. Patients previously exposed to both anti-TNFs 21. Previously unacceptable side effects or intolerance to all immunosuppressants (both thiopurines and methotrexate) 22. Treatment with vedolizumab or ustekinumab within 30 days 23. Active or latent tuberculosis (screening according to national guidelines) 24. Cardiac failure in NYHA stage III-IV 25. History of demyelinating disease 26. Recent live vaccination (= 4 weeks) 27. Patients with ongoing acute/chronic infection (including but not limited to HIV, hepatitis B and C) with the exception of chronic herpes labialis or cervical HPV 28. History of cancer in the last 5 years with the exception of non-melanoma skin cancer 29. Male patients with negative EBV serology Mesenchymal stem cell patients: 30. Presence of rectal ulcerations according current indication registration 31. Hypersensitivity to the product, bovine serum or any of the excipients (Dulbecco’s Modified Eagle’s Medium, containing amino acids, vitamins, salts and carbohydrates, and human albumin) 32. Age < 18 years old Hyperbaric oxygen patients: 33. Unfit for hyperbaric oxygen therapy as assessed by the hyperbaric physician 34. Contraindication for hyperbaric oxygen therapy: sensitivity to barotrauma, claustrophobia per assessment of hyperbaric oxygen specialists. 35. Age < 18 years old
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Presence and amount of inflammatory cell subtypes, stromal cells and identification of mucosal microbiome in rectal biopsies and fistula scrapings that relate to prediction of response to treatment for complex perianal Crohn’s fistulas. Response and remission will be measured by a combination of clinical and MRI endpoints. | — |
Secondary
| Measure | Time frame |
|---|---|
| - The proportion of patients with a combination of clinical and radiological remission (defined as fistula drainage assessment (FDA)-100% and remission according to the MAGNIFI-CD index *) and response (defined as FDA-50% or remission according to the MAGNIFI-CD index *, or FDA-50% and response according to the MAGNIFI-CD index*. All other combinations will be scored as non-responder. *Cut-off values for response and remission according to the MAGNIFI-CD index are currently under investigation. - The proportion of patients with radiological remission defined as a completely fibrotic tract on MRI at week 26 - The proportion of patients with clinical fistula response and remission measured by the perianal disease activity index (PDAI; defined as PDAI=4 for response and PDAI-50% for remission) at week 26 compared to baseline - Proportion of patients with symptomatic response and remission measured at week 26 compared to baseline by resp. a 25% and 50% reduction on a 10 cm patient scored visual analogue scale of global disease severity - Proportion of patients with symptomatic response and remission measured by the IBDQ-32 questionnaire (defined as IBDQ-32 27 for response) at week 26 compared to baseline - Changes in quality-of-life measured by the CAF-QoL questionnaire (Crohn’s Anal Fistula – Quality of Life score) at week 26 compared to baseline - Proportion of patients in luminal remission and response for Crohn’s disease activity at week 0, 9 and 26 measured by the Harvey-Bradshaw Index (HBI; defined as HBI < or = 4 for remission and HBI – 3 for response) - Proportion of patients achieving biochemical remission at week 9 and 26 (defined as serum C-reactive protein <5.0 mg/L and fecal calprotectin < 250 mg/g) - Time to biochemical remission (defined as serum C-reactive protein <5.0 mg/L and fecal calprotectin < 250 mg/g) - Adverse events | — |
Contacts
Public ContactLieven Mulders
Amsterdam UMC
Outcome results
None listed