nderstanding mechanisms of interventions and opportunities for personalized treatment in perianal fistulizing Crohn*s disease

Recruiting

• Conditions: perianal fistulzing Crohn's disease / perianal fistulas in Crohn's disease; 10017969

• Registration Number: NL-OMON50884
• Lead Sponsor: Academisch Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 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)

In this observational study we will monitor three control groups at one study
point. The following inclusion criteria will be used.

Patients with cryptoglandular fistulas without CD:
• Active cryptoglandular fistula, either superficial or complex
• No previous documentation of CD activity and a fecal calprotectin <250
• 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
• CD treatment naive patients (i.e., immunomodulators, anti-TNF, other
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
• CD treatment naive patients (i.e., immunomodulators, anti-TNF, other
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 stony
8. Enteric pathogens (such as Salmonella, Shigella, Yersinia, Campylobacter and
C. difficile) etected 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 anti-TNF
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)

Hyperbaric oxygen patients:
32. Unfit for hyperbaric oxygen therapy as assessed by the hyperbaric physician
33. Contraindication for hyperbaric oxygen therapy: sensitivity to barotrauma,
claustrophobia per assessment of hyperbaric oxygen specialists.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
<p>Presence and amount of inflammatory cell subtypes, stromal cells and<br /><br>identification of mucosal microbiome in rectal biopsies and fistula scrapings<br /><br>that relate to prediction of response to treatment for complex perianal Crohn*s<br /><br>fistulas. Response and remission will be measured by a combination of clinical<br /><br>and MRI endpoints.</p><br>