Minimally Invasive vs Open Surgery for Ulcerative Colitis

(FUNCTIon Trial)

Overseen By Anthony de Buck, MD, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mount Sinai Hospital, Canada

Must not be taking: Steroids

Disqualifiers: Colorectal cancer, PSC, FAP, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two surgical methods for treating ulcerative colitis or unclassified inflammatory bowel disease. It aims to determine if a less invasive surgery, transanal IPAA (Ileal Pouch-Anal Anastomosis), is as effective as the traditional laparoscopic surgery, transabdominal IPAA, in improving patient function post-surgery. Suitable candidates for this trial have ulcerative colitis unresponsive to medication and are scheduled for surgery. Researchers will monitor participants for a year to assess recovery and function after undergoing one of the two surgical methods. As an unphased trial, this study provides patients the chance to contribute to valuable research that could enhance surgical options for future patients.

Will I have to stop taking my current medications?

The trial requires that patients stop taking immunomodulating therapy, including steroids, before surgery. There is an 8-week washout period (time without taking certain medications) for all treatments before the pouch construction.

What prior data suggests that these surgical techniques are safe for ulcerative colitis patients?

Research has shown that the transanal ileal pouch-anal anastomosis (ta-IPAA) is generally safe for people with ulcerative colitis. In studies, patients who underwent this surgery experienced low rates of anastomotic leakage, where a surgical connection leaks fluid, indicating that the surgery is well-tolerated. Another study found that ta-IPAA has a good safety record, with positive outcomes both shortly after surgery and in the long term. Although this procedure is newer compared to traditional methods, early research suggests it is a safe option for many patients needing surgery for ulcerative colitis. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatment techniques for ulcerative colitis because they offer a less invasive approach compared to traditional methods. The transanal IPAA technique allows surgeons to access the lower rectum through the anus, which may reduce recovery time and postoperative complications. On the other hand, the transabdominal IPAA utilizes advanced tools like laparoscopy or even robotic assistance to perform the surgery, potentially offering more precision and less trauma than open surgery. These methods could lead to quicker recoveries and better overall outcomes for patients with ulcerative colitis.

What evidence suggests that this trial's treatments could be effective for ulcerative colitis?

Research has shown that a surgical procedure called transanal ileal pouch-anal anastomosis (ta-IPAA), which participants in this trial may receive, can improve life for people with ulcerative colitis (UC). Studies have found that ta-IPAA often leads to good outcomes after surgery, reducing issues like incontinence and leakage during sleep. Meanwhile, the traditional laparoscopic transabdominal IPAA (tabd-IPAA), another treatment option in this trial, has proven effective for many. The ta-IPAA method might offer similar or even better recovery and daily function. Patients who have undergone these surgeries reported better control over bowel movements and an improved quality of life. Although data on ta-IPAA remains limited, early results are promising for those who need this surgery. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-60 with Ulcerative Colitis or IBD unclassified, who need surgery and haven't responded to medical therapy. They must speak English or the center's primary language and give informed consent. Excluded are those with certain genetic conditions, cancer, severe lung disease, pregnancy, lactation, steroid use without an 8-week washout period before surgery.

Inclusion Criteria

Provide informed consent

My treatment plan involves 1 to 3 stages.

My ulcerative colitis or IBD is not responding to treatment or has precancerous changes.

Exclusion Criteria

Pregnancy and lactation (tested by a urinary pregnancy test)

I need surgery that involves hand-stitching parts of my intestines together.

I am scheduled for or have had redo-pouch surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants undergo either transanal or transabdominal ileal pouch-anal anastomosis (IPAA) surgery

Hospitalization period

In-hospital stay for surgery and initial recovery

Postoperative Monitoring

Participants are monitored for perioperative events and complications

30 days

Regular in-person visits as per hospital protocol

Follow-up

Participants are monitored for functional outcomes and clinical events

12 months

Follow-up visits at 6 weeks, 3 months, 6 months, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Transanal and Laparoscopic or Open Ileal Pouch-Anal Anastomosis

Trial Overview The FUNCTIon trial compares two surgical techniques for creating a pelvic pouch in patients: transanal (ta-IPAA) versus laparoscopic (tabd-IPAA). It aims to see if ta-IPAA has equal or better functional outcomes after one year using the COREFO questionnaire. The study will randomly assign participants to either group across three hospitals.

How Is the Trial Designed?

Group I: transanal IPAA Experimental Treatment 1 Intervention

In the experimental arm, patients will undergo transanal dissection of the distal part of the rectum. After proctectomy, an ileal pouch-anal anastomosis (IPAA) will be created. A Gelpoint Path will be used to create access through the anus. Postoperative care will occur following the hospital specific protocols.

Group II: transabdominal IPAA Active Control 1 Intervention

In the control group, proctectomy will occur through abdominal dissection (laparoscopy, single port laparoscopy, robotic or open). Postoperative care will occur following the hospital specific protocols.

Transanal and Laparoscopic or Open Ileal Pouch-Anal Anastomosis is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Ileal Pouch-Anal Anastomosis for:

• Ulcerative Colitis
• Familial Adenomatous Polyposis
• Inflammatory Bowel Disease Unclassified

Approved in United States as Ileal Pouch-Anal Anastomosis for:

• Ulcerative Colitis
• Familial Adenomatous Polyposis
• Inflammatory Bowel Disease Unclassified

Approved in Canada as Ileal Pouch-Anal Anastomosis for:

• Ulcerative Colitis
• Familial Adenomatous Polyposis
• Inflammatory Bowel Disease Unclassified

Who Is Running the Clinical Trial?

Mount Sinai Hospital, Canada

Lead Sponsor

Trials

210

Recruited

70,700+

Universitaire Ziekenhuizen KU Leuven

Collaborator

Trials

1,048

Recruited

1,658,000+

Janindra Warusavitarne

Collaborator

Trials

1

Recruited

50+

Gabriele Bislenghi

Collaborator

Trials

1

Recruited

50+

Andre D'Hoore

Collaborator

Trials

1

Recruited

50+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

St Mary's Hospital, London

Collaborator

Trials

10

Recruited

8,800+

Mantaj S. Brar

Collaborator

Trials

1

Recruited

50+

Philip Fleshner

Collaborator

Trials

1

Recruited

50+

Karen Zaghiyan

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

After 30 years, 93.3% of patients who underwent ileal pouch-anal anastomosis (IPAA) still had a functioning pouch, demonstrating the long-term durability of this surgical procedure for chronic ulcerative colitis.

Quality of life scores remained stable over the 30 years post-surgery, indicating that while stool frequency increased slightly, overall functional outcomes and patient satisfaction did not significantly decline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results at Up to 30 Years After Ileal Pouch-Anal Anastomosis for Chronic Ulcerative Colitis. Lightner, AL., Mathis, KL., Dozois, EJ., et al.[2018]

Laparoscopic ileal pouch-anal anastomosis (LAP-IPAA) is as safe as conventional open IPAA, with similar rates of postoperative complications and no mortality reported in a study of 300 patients.

Patients undergoing LAP-IPAA experienced significantly faster recovery, including shorter time to regular diet, ileostomy output, and hospital stay, compared to those who had open IPAA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, feasibility, and short-term outcomes of laparoscopic ileal-pouch-anal anastomosis: a single institutional case-matched experience. Larson, DW., Cima, RR., Dozois, EJ., et al.[2022]

Pouch-related adenocarcinomas are rare complications following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, with a cumulative incidence of 0.33% after 50 years and primarily arising from the anorectal mucosa.

The strongest risk factor for developing pouch-related adenocarcinoma is the presence of neoplasia in the colectomy specimen, with mucosectomy not eliminating cancer risk but increasing the likelihood of cancer from residual anorectal mucosa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of cuff and pouch cancer in patients with ileal pelvic pouch for ulcerative colitis. Selvaggi, F., Pellino, G., Canonico, S., et al.[2018]

Patients undergoing laparoscopic ileal pouch anal anastomosis (LAP-IPAA) experienced faster recovery times, including shorter times to first walking and food intake compared to those who had open IPAA, indicating a more efficient postoperative recovery process.

LAP-IPAA was associated with significantly lower levels of inflammatory markers (interleukin-6, interleukin-1ra, and C-reactive protein) shortly after surgery, suggesting that it results in a reduced systemic inflammatory response compared to open IPAA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Acute-phase Response in Laparoscopic and Open Ileal Pouch Anal Anastomosis in Patients With Ulcerative Colitis: A Case-matched Comparative Study. Okita, Y., Araki, T., Hiro, J., et al.[2015]

In a study of 100 patients who underwent ileal pouch-anal anastomosis (IPAA) between 1990 and 1997, pelvic sepsis developed in 12 patients, but it did not significantly affect long-term pouch function or quality of life.

The study found no differences in pouch evacuation frequency, incontinence, or other functional outcomes between patients with and without postoperative pelvic sepsis, suggesting that pelvic sepsis may not impair long-term results after IPAA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ileal pouch-anal anastomosis (IPAA): functional outcome after postoperative pelvic sepsis. A prospective study of 100 patients. Hallberg, H., Ståhlberg, D., Akerlund, JE.[2018]

Ileal pouch anal anastomosis (IPAA) is a highly effective treatment for chronic ulcerative colitis and other related conditions, with 95% of patients reporting good or excellent functional outcomes and quality of life after surgery.

In a study of 3707 patients, early complications occurred in 33.5% of cases, but the mortality rate was very low at 0.1%, indicating that while there are risks, IPAA is generally safe and has a low pouch failure rate of 5.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ileal pouch anal anastomosis: analysis of outcome and quality of life in 3707 patients. Fazio, VW., Kiran, RP., Remzi, FH., et al.[2022]

A survey of 40 Canadian and 873 American colorectal surgeons revealed that Canadian surgeons are more likely to perform ileal pouch anal anastomosis (IPAA) alone (44%) compared to American surgeons (26%) when a tension-free IPAA is possible after prior colectomy.

In cases involving patients on high doses of prednisone, Canadian surgeons preferred subtotal colectomy with end ileostomy (45%) significantly more than American surgeons (14%), indicating notable differences in surgical approaches between the two countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical management of ulcerative colitis: a comparison of Canadian and American colorectal surgeons. Richardson, D., deMontbrun, S., Johnson, PM.[2021]

In a study of 116 patients who underwent ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, the procedure showed a high preservation rate of 93.1% after 20 years, indicating its long-term effectiveness.

Despite some early complications, most patients reported satisfactory to acceptable long-term intestinal function and a good quality of life, with a median global quality of life score of 0.8 out of 1.0.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ileal pouch-anal anastomosis in ulcerative colitis: outcomes, functional results, and quality of life in patients with more than 10-year follow-up. Carcamo, L., Miranda, P., Zúñiga, A., et al.[2021]

In a study of 1310 patients who underwent hand-sewn ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, postoperative complications decreased significantly over time, with pelvic sepsis rates dropping from 7% to 3% between 1981-1985 and 1991-1994.

After an average follow-up of 6.5 years, the functional outcomes remained stable, with patients averaging 5 stools per day, but the cumulative probability of pouch failure increased to 9% by 10 years, indicating that while complications may decrease with experience, long-term pouch failure rates can rise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. Meagher, AP., Farouk, R., Dozois, RR., et al.[2022]

In a study comparing 23 patients undergoing total laparoscopic ileal pouch anal anastomosis (IPAA) to 22 patients undergoing the open approach, the laparoscopic method resulted in a lower overall major complications rate (5 vs. 9), although this difference was not statistically significant.

Patients who had the laparoscopic approach experienced a significantly shorter mean hospital stay (27 days) compared to those who had the open approach (39 days), indicating that laparoscopic surgery may lead to quicker recovery times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laparoscopic 3-step restorative proctocolectomy: comparative study with open approach in 45 patients. Ouaïssi, M., Lefevre, JH., Bretagnol, F., et al.[2008]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40816645/

Functional Outcomes of Transanal Ileal Pouch Anal ... Purpose: This single-centre, comparative cohort study aims to compare the functional outcomes in patients who have undergone laparoscopic ...

2. academic.oup.com academic.oup.com/bjsopen/article/9/1/zrae111/7972470

Ileal pouch-anal anastomosis for ulcerative colitis: 30-year ... This study reviews the evolution of proctocolectomy with ileal pouch-anal anastomosis surgery and its outcomes over three decades at the

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6710180/

Ileal-anal pouches: A review of its history, indications, and ... The ileal pouch anal anastomosis (IPAA) has revolutionised the surgical management of ulcerative colitis (UC) and familial adenomatous polyposis (FAP).

4. tgh.amegroups.org tgh.amegroups.org/article/view/8111/html

Restorative pouch surgery following proctocolectomy for ... There is also evidence that stapled IPAA results in better functional outcomes with lower incidence of incontinence and nocturnal seepage (8). Though the J- ...

5. coloproctol.org coloproctol.org/journal/view.php?doi=10.3393/ac.2020.08.26

Ileal Pouch-Anal Anastomosis for Ulcerative Colitis We report outcomes and evaluate patient factors and the impact of surgical evolution on outcomes in consecutive ulcerative colitis patients who ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11070401/

Transanal ileal pouch-anal anastomosis: A systematic ... We performed a systematic review assessing technical approaches to transanal IPAA (Ta-IPAA) and meta-analysis comparing outcomes to transabdominal (abd-IPAA) ...

7. pssjournal.biomedcentral.com pssjournal.biomedcentral.com/articles/10.1186/s13037-021-00306-5

Safety of transanal ileal pouch-anal anastomosis for ulcerative ... The objective of this study was to determine anastomotic leakage rates and treatment after taIPAA as well as short- and long-term pouch function.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1590865824010120

The impact of colectomy and restorative procedure on ... Data on 379 patients who underwent total abdominal colectomy and proctectomy with ileo-pouch-anal-anastomosis (IPAA) with or without diverting ileostomy were ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37039927/

Functional outcomes after transanal ileal pouch-anal ... The transanal approach to ileal pouch-anal anastomosis (Ta-IPAA) for ulcerative colitis was introduced in 2015 and has since been shown to be a safe and ...