COlonic Salvage by Therapeutic Appendectomy.

Study Purpose

Rationale: The annual incidence of ulcerative colitis (UC) amounts to 6-8 new cases per 100.000. Patients are initially treated medically, and colitis refractory to medical management is treated surgically, mostly by means of an (emergency) colectomy or a proctocolectomy with ileal J-pouch anastomosis. Over the past 10 years evidence has been accumulating indicating that the appendix has an immunomodulatory role in patients with UC reducing the need for medication and perhaps even colectomy. Objective: The objective of this prospective observational cohort study is to evaluate the effect of appendectomy on the disease course of patients with active ulcerative colitis despite standard step-up treatment including biologicals. The second objective is to determine if histological inflammation in the appendix resection specimens can be reliably predicted by pre-operative endoscopic biopsies of the appendix and correlated to clinical and pathological response after appendectomy. Study design: The design of the study is a prospective observational cohort study of 80 consecutive patients. Study population: Sixty patients of 18 years and older, with established diagnosis of UC and ongoing disease activity despite standard step-up treatment including biologicals. Furthermore, histological characteristics in appendix biopsies of 10 patients with non-active UC and 10 'healthy control' patients (e.g. patients undergoing endoscopy for polyps) will be evaluated and used as a reference control group. Intervention: Patients will undergo laparoscopic appendectomy in clinical or day care setting. Main study parameters/objectives: The primary outcome parameter is the number of patients achieving remission (Total Mayo score ≤2) 12 months after appendectomy. Secondary endpoints are reduction of medical therapy, the disease activity as measured with the Mayo score, colectomy rate, the health related quality of life and costs (EQ-5D, EORTC-QLQ-C30-QL and IBDQ), and histological appendix characteristics predictive of response.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion criteria (study group)

  • - Age 18 years and older - Established diagnosis of UC - Active disease (defined both clinically and endoscopically as Mayo-score ≥5 with endoscopy score of 2 or 3) despite standard step-up treatment including biologicals - Obtained written informed consent Inclusion criteria (control group) - Age 18 years and older - UC patients with non-active disease (defined both clinically and endoscopically as Mayo-score ≤5 with endoscopy score of 0 or 1) or non-UC patients with polyps - Planned colonoscopy - Open appendix lumen with diameter large enough to slide scope in - Obtained written informed consent Exclusion criteria (study group) - Prior appendectomy or other abdominal surgery by laparotomy.
  • - Suspicion of Crohn's disease.
  • - Toxic megacolon or severe acute colitis necessitating clinical admission - Patients with active extra-intestinal infections, liver or kidney failure, mayor lung and heart co-morbidity.
  • - Insufficient command of Dutch or cognitively unable to complete Dutch questionnaires Exclusion criteria (control group) - Prior appendectomy.
  • - Suspicion of Crohn's disease.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03912714
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Christianne Buskens, MD, PhD
Principal Investigator Affiliation Amsterdam Medical Centre
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOther
Overall Status Recruiting
Countries Netherlands
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Colitis, Ulcerative
Additional Details

The study is designed as a prospective observational series including patients with active ulcerative colitis despite standard step-up treatment including biologicals. Sixty consecutive patients who are refractory to medical treatment will be recruited to evaluate the effect of the appendectomy on the disease course. Eligible patients will be counselled at the outpatient clinics. Patients with presumed therapy-refractory inflammation will undergo ileocolonoscopy, which is part of standard daily practice. When informed consent is given, the presence of a PARP will be documented, and additional biopsies of the appendix and coecal base will be taken, to determine histological inflammation grade. Active disease is required for inclusion, and is defined as a combined clinical and endoscopic Mayo-score of ≥5 with an endoscopic subscore of 2 or 3. After inclusion, a laparoscopic appendectomy will be performed within 9 weeks. Patients will be followed every 3 months after laparoscopic appendectomy to assess the patients' clinical condition and the non-invasive Mayo score. According to standard practice evaluating therapy change, a sigmoidoscopy will be performed within 6 months and a full ileocolonoscopy at 12 months, including biopsies of the colon and coecal base, to assess mucosal appearance and complete the Mayo score. Postoperatively, patients will receive the similar medical treatment as given pre-appendectomy. If medication can be tapered post-appendectomy, this will be done according to the experience of the treating physician and current guidelines. Patients will complete health related quality of life questionnaires (EQ-5D, EORTC-QLQ-C30-QL and IBDQ) via email or a telemedicine application (MyIBDcoach) at inclusion and at 3, 6 and 12 months follow-up. The pre-operative endoscopic biopsies of the appendix will be used to determine if histological inflammation in the appendix resection specimens can be reliably predicted. Histological findings in the resection specimens will be correlated to clinical and pathological response after appendectomy. Furthermore, in 20 patients who are planned for colonoscopy (10 patients with non-active UC and 10 non-UC patients with polyps) additional appendix biopsies will be taken to use as a reference control group. Therefore, a total of 80 patients will be recruited for this study.

Arms & Interventions

Arms

Experimental: Laparoscopic appendectomy

Laparoscopic appendectomy in therapy refractory ulcerative colitis patients after pre-operative endoscopic biopsies of the appendix

Active Comparator: Non-active UC

Patients with non-active ulcerative colitis planned for surveillance colonoscopy will have additional endoscopic appendix biopsies to evaluate the histological characteristics of the appendix.

Active Comparator: Healthy control

'Healthy control' patients (i.e. patients planned for colonoscopy for polyps) will have additional endoscopic appendix biopsies to evaluate the histological characteristics of the appendix.

Interventions

Procedure: - Laparoscopic appendectomy

Surgery will be performed under general anaesthesia. The laparoscopic appendectomy can be performed with the use of 3 trocars; one subumbilical, one suprapubic and one in the lower right quadrant of the abdomen. The appendix is removed using a laparoscopic endostapler enabling a safe and complete appendectomy with the cross stapling line at coecal base. Laparoscopic appendectomy will be performed by a gastrointestinal surgeon with sufficient experience in laparoscopic appendectomies (>20).

Procedure: - Endoscopic appendix biopsies

Appendix biopsies will only be taken when the scope easily slides into the lumen of the appendix (the scope will not be pushed into the appendix lumen)

Contact a Trial Team

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International Sites

Amsterdam UMC, Amsterdam, Netherlands

Status

Recruiting

Address

Amsterdam UMC

Amsterdam, , 1105AZ

Site Contact

Lianne Heuthorst, MD

l.heuthorst@amc.uva.nl

0031207326818

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