- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT07640113
Impact of Ambulatory Physiological Stimulation of the Efferent Limb Prior to Ileostomy Closure on Colorectal Microbiota Composition and Histopathological Findings (STIMIC)
The STIMIC Trial: A Multicenter Randomized Control Trial Evaluating the Impact of Ambulatory Physiological Stimulation of the Efferent Limb Prior to Ileostomy Closure on Colorectal Microbiota Composition and Histopathological Findings
BACKGROUND Loop ileostomies are a type of stoma frequently used to protect high-risk colorectal anastomoses (surgical reconnection of the intestines), for example following rectal cancer resection. Temporary diversion of intestinal transit does not reduce the risk of anastomotic failure, but it does lower the morbidity and mortality associated with potential pelvic sepsis. Unfortunately, a second surgical procedure is required to restore intestinal continuity, and this carries its own risk of complications, the most common being postoperative ileus (temporary paralysis of bowel motility associated with abdominal distension, absence of bowel movements, nausea, and vomiting), which occurs in up to 20% of cases.
Several strategies have been proposed to reduce this problem, including stimulation of the efferent limb of the ileostomy (the part that is connected to the unused colon). This intervention consists of instilling a substance through the efferent limb of the ileostomy into the colon, simulating natural intestinal transit. It emerged as a harmless alternative aimed at reversing changes in the excluded colon in preparation for restoration of intestinal continuity. Several Spanish studies have investigated this technique, concluding that it is safe and significantly reduces the rate of postoperative ileus, thereby shortening hospital stay. Regarding the mechanism by which this intervention may be effective, there are studies investigating the changes that occur during diversion of intestinal transit:
- Histopathology: reduced muscular contractility and the presence of intestinal villi in the efferent intestinal limb and excluded colon, which improve once intestinal flow is restored.
- Microbiome: significant loss of microbiota in the defunctionalized colon, which progressively recovers with natural intestinal transit and reintroduction of a fiber-rich diet.
Structural and microbiota-related changes favor the development of diversion colitis, a condition associated with erratic bowel habits once intestinal transit is restored. In an attempt to reverse this condition, several products have been tested for stimulation of the efferent limb of the ileostomy: probiotics, short chain fatty acids, saline solution with a thickening agent, and the patient's own intestinal contents, a well-tolerated and effective technique, in some cases superior to saline-based alternatives.
Overall, the available evidence is of low quality due to the limited number of patients studied and protocol variability. For this reason, we propose the implementation of a protocol for stimulation of the distal ileostomy limb prior to ileostomy closure, either with saline solution and thickening agent (the most widely described technique in the literature) or physiological stimulation using the patient's own intestinal contents.
The protocol consists of several sessions in which the instilled volume is progressively increased. This intervention will be performed on an outpatient basis, once daily, during the two weeks prior to surgery.
This process promotes the onset of bowel movements through the anus, which progressively become more formed and less frequent, approaching a more normal bowel habit. Only minor adverse effects have been described with this technique, including cramp-like abdominal pain in 27.6% of sessions. Recently, a nationwide study confirmed the favorable clinical outcomes following distal ileostomy limb stimulation before ileostomy closure. However, to our knowledge, no studies have evaluated its effect on intestinal microbiota.
HYPOTHESIS Distal limb stimulation of the ileostomy before its closure helps in the recovery of the colorectal microbiome and tissue. This associates with lower postoperative complications, specially postoperative ileus.
OBJECTIVES To gain knowledge regarding changes in intestinal microbiota composition before and after stimulation, in order to better understand recovery of intestinal function following this procedure. We will also analyze outcomes after ileostomy closure following efferent limb stimulation, determining the incidence of postoperative complications, particularly postoperative ileus.
METHODOLOGY
Patients will be randomly assigned to one of three groups:
- Control (no intervention other than the usual preoperative protocol)
- Stimulation with serum and thickener
- Stimulation with own stoma output
Samples will be collected in all patients:
- Stoma output
- Stool, before stimulation, if performed
- Stool, after stimulation, if performed
- Stool, a month after surgery
For a group of patients, the ones recruited at Hospital Clínic, rectal biopsies will also be collected before and after stimulation, to compare the effect of the treatment in the colonic tissue. We will collect clinical data during the whole process regarding postoperative complications.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiekontakt
- Navn: Romina Pena, MD
- Telefonnummer: +34 617333153
- E-mail: PENA@clinic.cat
Undersøgelse Kontakt Backup
- Navn: Miguel Pera, MD, PhD
- Telefonnummer: 5559 +34 932275400
- E-mail: PERA@clinic.cat
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Beskrivelse
Inclusion criteria:
- Patients 18 yo and older, with a loop ileostomy after colorectal surgery for malignant or benign disease and a barium enema that rules out colorectal anastomotic leak or stenosis.
- Patients must be self-sufficient in their stoma care or dispose of assistance by a family member or healthcare provider.
- Patients must reside no further than 50km from the hospital and dispose of postoperative home-assistance by a family member or healthcare provider.
Exclusion criteria:
- Patients with a terminal ileostomy or a closed distal limb, inaccesible to preoperative stimulation.
- Patients with the diagnosis of inflammatory bowel disease.
- Patients incapable of comprehending or signing the informed consent.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Grundvidenskab
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Ingen indgriben: Control
No efferent limb stimulation.
|
|
|
Aktiv komparator: Serum stimulation
Efferent limb stimulation with serum and thickener.
|
The intervention has been described in previous studies, but the investigation of the microbiome changes associated with the obtained clinical results hasn't been described to date.
Also, a study with three arms hasn't been published to date.
Andre navne:
|
|
Aktiv komparator: Physiological stimulation
Efferent limb stimulation with the patient's own stoma output.
|
The intervention has been described in previous studies, but the investigation of the microbiome changes associated with the obtained clinical results hasn't been described to date.
Also, a study with three arms hasn't been published to date.
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Changes in colorectal microbiome before and after efferent limb stimulation prior to stoma closure.
Tidsramme: From enrollment to the end of follow-up at 3 months.
|
Descriptive analysis of the microbiome profiles of the three groups of patients (control, stimulation with serum, stimulation with own stoma output).
|
From enrollment to the end of follow-up at 3 months.
|
|
Changes in colorectal tissue before and after efferent limb stimulation prior to stoma closure.
Tidsramme: From the time of first biopsy (before stimulation) to the second one (surgery day).
|
Description of the tissue obtained by biopsy of the rectum, before and after stimulation of the ileostomy.
|
From the time of first biopsy (before stimulation) to the second one (surgery day).
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Postoperative complications after stoma closure.
Tidsramme: From the surgery (ileostomy closure) to 30 days follow-up.
|
Incidence of postoperative ileus and surgical site infection.
|
From the surgery (ileostomy closure) to 30 days follow-up.
|
|
Functional outcomes after efferent limb stimulation (LARS score)
Tidsramme: From enrollment to the end of follow-up a 3 months.
|
Description of the funcional (defecatory) outcomes after ileostomy closure. LARS (Low Anterior Resection Syndrome) score: total score ranges from 0-42 points (0-20 is equivalent no LARS, 21-29 points to minor LARS, and 30-42 to major LARS). |
From enrollment to the end of follow-up a 3 months.
|
|
Functional outcomes after efferent limb stimulation (Vaizey score)
Tidsramme: From enrollment to the end of follow-up at 3 months.
|
Description of the funcional (defecatory) outcomes after ileostomy closure. Vaizey score (also known as the St. Mark's Incontinence Score): total score ranges from 0 (perfect continence) to 24 points (severe incontinence). |
From enrollment to the end of follow-up at 3 months.
|
Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Romina Pena, MD, Hospital Clinic of Barcelona
Publikationer og nyttige links
Generelle publikationer
- Matthiessen P, Hallbook O, Rutegard J, Simert G, Sjodahl R. Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer: a randomized multicenter trial. Ann Surg. 2007 Aug;246(2):207-14. doi: 10.1097/SLA.0b013e3180603024.
- Kim MJ, Park JW, Lee MA, Lim HK, Kwon YH, Ryoo SB, Park KJ, Jeong SY. Two dominant patterns of low anterior resection syndrome and their effects on patients' quality of life. Sci Rep. 2021 Feb 11;11(1):3538. doi: 10.1038/s41598-021-82149-9.
- Rodriguez-Padilla A, Morales-Martin G, Perez-Quintero R, Gomez-Salgado J, Balongo-Garcia R, Ruiz-Frutos C. Postoperative Ileus after Stimulation with Probiotics before Ileostomy Closure. Nutrients. 2021 Feb 15;13(2):626. doi: 10.3390/nu13020626.
- Garfinkle R, Savage P, Boutros M, Landry T, Reynier P, Morin N, Vasilevsky CA, Filion KB. Incidence and predictors of postoperative ileus after loop ileostomy closure: a systematic review and meta-analysis. Surg Endosc. 2019 Aug;33(8):2430-2443. doi: 10.1007/s00464-019-06794-y. Epub 2019 Apr 17.
- Rombey T, Panagiotopoulou IG, Hind D, Fearnhead NS. Preoperative bowel stimulation prior to ileostomy closure to restore bowel function more quickly and improve postoperative outcomes: a systematic review. Colorectal Dis. 2019 Sep;21(9):994-1003. doi: 10.1111/codi.14636. Epub 2019 May 7.
- Fernandez Lopez F, Gonzalez Lopez J, Paz Novo M, Ladra Gonzalez MJ, Paredes Cotore J. Stimulation the efferent limb before loop ileostomy closure with short chain fatty acids. Cir Esp (Engl Ed). 2019 Jan;97(1):59-61. doi: 10.1016/j.ciresp.2018.06.018. Epub 2018 Oct 15. No abstract available. English, Spanish.
- Lloyd AJ, Hardy NP, Jordan P, Ryan EJ, Whelan M, Clancy C, O'Riordan J, Kavanagh DO, Neary P, Sahebally SM. Efferent limb stimulation prior to loop ileostomy closure: a systematic review and meta-analysis. Tech Coloproctol. 2023 Dec 14;28(1):15. doi: 10.1007/s10151-023-02875-2.
- Ocana J, Garcia-Perez JC, Labalde-Martinez M, Rodriguez-Velasco G, Moreno I, Vivas A, Clemente-Esteban I, Ballestero A, Abadia P, Ferrero E, Fernandez-Cebrian JM, Die J. Can physiological stimulation prior to ileostomy closure reduce postoperative ileus? A prospective multicenter pilot study. Tech Coloproctol. 2022 Aug;26(8):645-653. doi: 10.1007/s10151-022-02620-1. Epub 2022 May 21.
- Garfinkle R, Demian M, Sabboobeh S, Moon J, Hulme-Moir M, Liberman AS, Feinberg S, Hayden DM, Chadi SA, Demyttenaere S, Samuel L, Hotakorzian N, Quintin L, Morin N, Faria J, Ghitulescu G, Vasilevsky CA, Boutros M; Bowel Stimulation Research Collaborative. Bowel stimulation before loop ileostomy closure to reduce postoperative ileus: a multicenter, single-blinded, randomized controlled trial. Surg Endosc. 2023 May;37(5):3934-3943. doi: 10.1007/s00464-022-09510-5. Epub 2022 Aug 19.
- Charbonneau J, Morin G, Pare XG, Frigault J, Drolet S, Bouchard A, Rouleau-Fournier F, Bouchard P, Thibault C, Letarte F. Loop Ileostomy Closure as a 23-Hour Stay Procedure With Preoperative Efferent Limb Enteral Stimulation: A Randomized Controlled Trial. Dis Colon Rectum. 2024 Mar 1;67(3):466-475. doi: 10.1097/DCR.0000000000003111. Epub 2023 Nov 16.
- Bracey E, Chave H, Agombar A, Sleight S, Dukes S, Bryan S, Branagan G. Ileostomy closure in an enhanced recovery setting. Colorectal Dis. 2015 Oct;17(10):917-21. doi: 10.1111/codi.12989.
- Arredondo J, Uriz A, Oliva I, Martin JI, Iglesias CN, Choolani E, Valle A, Rivera J, Jeri-McFarlane S, Romero JM, Gonzalez C, Alvarellos A, Tasende M, Gomez L, Lazaro L, Montcusi B, Tejedor P, Trujillo-Diaz J, de la Hermosa AR, Baixauli J, Nunez-Cordoba JM, Aliseda D; ILEOSTIM Trial Group. The ILEOSTIM trial: A multicentre randomised controlled trial evaluating the impact of efferent loop stimulation prior to ileostomy reversal on postoperative ileus. Colorectal Dis. 2026 May;28(5):e70448. doi: 10.1111/codi.70448.
- Liu Z, Fang L, Lv L, Niu Z, Hou L, Chen D, Zhou Y, Guo D. Self-administered succus entericus reinfusion before ileostomy closure improves short-term outcomes. BMC Surg. 2021 Dec 28;21(1):440. doi: 10.1186/s12893-021-01444-4.
- Xia F, Zou Y, Zhang Q, Wu J, Sun Z. A novel nomogram to predict low anterior resection syndrome (LARS) after ileostomy reversal for rectal cancer patients. Eur J Surg Oncol. 2023 Feb;49(2):452-460. doi: 10.1016/j.ejso.2022.10.015. Epub 2022 Oct 23.
- Vogel I, Reeves N, Tanis PJ, Bemelman WA, Torkington J, Hompes R, Cornish JA. Impact of a defunctioning ileostomy and time to stoma closure on bowel function after low anterior resection for rectal cancer: a systematic review and meta-analysis. Tech Coloproctol. 2021 Jul;25(7):751-760. doi: 10.1007/s10151-021-02436-5. Epub 2021 Apr 1.
- Abrisqueta J, Abellan I, Lujan J, Hernandez Q, Parrilla P. Stimulation of the efferent limb before ileostomy closure: a randomized clinical trial. Dis Colon Rectum. 2014 Dec;57(12):1391-6. doi: 10.1097/DCR.0000000000000237.
- Beamish EL, Johnson J, Shih B, Killick R, Dondelinger F, McGoran C, Brewster-Craig C, Davies A, Bhowmick A, Rigby RJ. Delay in loop ileostomy reversal surgery does not impact upon post-operative clinical outcomes. Complications are associated with an increased loss of microflora in the defunctioned intestine. Gut Microbes. 2023 Jan-Dec;15(1):2199659. doi: 10.1080/19490976.2023.2199659.
- Ekelund KM, Ekblad E. Structural, neuronal, and functional adaptive changes in atrophic rat ileum. Gut. 1999 Aug;45(2):236-45. doi: 10.1136/gut.45.2.236.
- Courtier R, Pares D, Silva CA, Gil MJ, Pascual M, Alonso S, Pera M, Grande L. [Clinical results of loop ileostomy closures in rectal cancer surgical patients. Effect of chemotherapy in the waiting period]. Cir Esp. 2010 Nov;88(5):308-13. doi: 10.1016/j.ciresp.2010.08.001. Spanish.
- Sharma A, Deeb AP, Rickles AS, Iannuzzi JC, Monson JR, Fleming FJ. Closure of defunctioning loop ileostomy is associated with considerable morbidity. Colorectal Dis. 2013 Apr;15(4):458-62. doi: 10.1111/codi.12029.
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Andre undersøgelses-id-numre
- HCB/2026/0615
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
IPD-delingstidsramme
IPD-delingsadgangskriterier
IPD-deling Understøttende informationstype
- STUDY_PROTOCOL
- ICF
- CSR
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