Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III Multicenter, Single Blind, Randomized, Comparative and add-on Clinical Trial, in Three Parallel Groups, to Evaluate Efficacy and Safety of a New Therapy With Adipose-derived Autologous Stem Cells for the Treatment of Complex Perianal Fistulas in Patients Without Inflammatory Bowel Disease
Brief Summary: Anal fistula is defined as an abnormal communication between the anal canal and the perianal skin. Adipose-derived stem cells are a new therapy for the closure of these fistulas. This study will test the safety and efficacy of ASCs (adipose stem cells) in the treatment of patients without Crohn´s disease.


Options:
A: Inclusion Criteria:

* 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:
* 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

Exclusion Criteria:

* 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
  * 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
B: Inclusion Criteria:

1. Patient with a complex perianal fistula. A complex perianal fistula must meet one of the following:

   * No fistula tract is palpated under the perianal skin or tract parallel to the rectum on examination with a stylet.
   * Associated anal incontinence in transsphincteric fistulas.
   * Risk factors for anal incontinence.
   * At least one prior surgery for a fistulous disease.
   * Suprasphincteric tracts shown by an image test.
2. Women of childbearing age should have a negative serum or urine pregnancy test (sensitive to 25IU of hCG) and not be lactating before study entry. Both men and women should use adequate birth control methods as defined by the investigator.
3. Seton presence is allowed at the time of study entry and until cells (in groups receiving ASCs) or Fibrin adhesive are implanted.
4. No condition that may prevent the patient from following the study procedures until 26 weeks of follow-up are completed is foreseen.
5. Patient should give his/her signed, written informed consent. -

Exclusion Criteria:

1. Patient has been diagnosed with IBD
2. Patient has a rectovaginal fistula
3. Patient is pregnant or lactating woman
4. Patient has acute sepsis at the time of study entry
5. A liposuction to draw at least 100 cc of fat from the abdominal wall is not technically feasible.
6. Patient needs surgery in the perianal region for reasons other than fistulas
7. Presence of two or more complex perianal fistulas
8. Patient has collections \> 2 cm in MRI. If such collections exist, the surgeon may perform a complete toilette of the area.
9. Patient is allergic to local anesthetics or Gadolinium (MRI contrast agent).
10. MRI is not technically feasible.
11. Patient has abused alcohol or other addictive substances within 6 months of study entry.
12. Patient has active or latent infection by HIV, HBV or HCV.
13. Patient has undergone major surgery or sustained a severe trauma, in the investigator's judgment, within 28 days of recruitment.
14. Patient is receiving or has received immunomodulatory treatment for reasons other than the fistula within 6 months of study entry.
15. Patient has a malignant tumour, except for basal or squamous cell carcinoma of the skin, or has a prior history of a malignant tumour, except if the tumour has been in remission for at least the past 5 years.

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C: Inclusion Criteria:

1. Age 18 to 80
2. Diagnosis of moderately to severely active Crohn's disease (CD)
3. CD involvement of the ileum and/or colon
4. Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents, within protocol-specified parameters:

   1. Immunomodulators
   2. Tumor necrosis factor-alpha (TNFα) antagonists
   3. Corticosteroids
5. May be receiving a therapeutic dose of conventional therapies for irritable bowel disease (IBD) defined by the protocol

Exclusion Criteria

1. Evidence of abdominal abscess at the initial screening visit, other than a minimum of 10 aphthous ulcerations involving a minimum of 10 contiguous cm of intestine
2. Extensive colonic resection, subtotal or total colectomy
3. History of \>3 small bowel resections or diagnosis of short bowel syndrome
4. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
5. Have received non permitted IBD therapies within either 30 or 60 days, depending on the medication, as stated in the protocol
6. Chronic hepatitis B or C infection
7. Active or latent tuberculosis
D: Inclusion Criteria:

* Clinical diagnosis of Crohn´s Disease
* presence of complex Crohn´s Disease fistulas
* fistulas refractory to standard surgical intervention, including long-term seton and regular curettage, and/or medical treatment.

Exclusion Criteria:

- Fistulas developed following proctectomy were excluded.

Answer: B