Amsterdam Fistula Biology

Recruiting

• Conditions: Complex perianal Crohn's disease

• Registration Number: NL-OMON26943
• Lead Sponsor: Amsterdam UMC loc AMC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 28 February 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 104

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 <250 (19)
• Age 16 y/o or older

Patients with CD with active proctitis and without perianal CD
• Confirmed diagnosis of CD with previously documented luminal inflammation and rectal ulcerations >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

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

Study & Design

• Study Type: Observational non invasive
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.