The Protective Role of Preoperative Stimulation of GABA Before Ileostomy Closure
The goal of this clinical trial is to explore whether preoperative gamma aminobutyric acid (GABA) lavage of the diverted colon improved postoperative bowel recovery, with time to first flatus as the primary outcome. Participants will be divided into two groups. One group included patients treated with stimulation of GABA prior to ileostomy reversal surgery; the other control group was stimulated with 0.9% saline. Researchers will compare incidence of complications such as postoperative ileus, diarrhea and other parameters such as time to tolerating a diet, start of the passage of flatus, start of the passage of stool, postoperative stay, multi-omic profiling of the gut microbiome and metabolome and serum biochemical measurements evaluating potential systemic effects, etc.
Descripción general del estudio
Estado
Condiciones
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Shandong
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Jinan, Shandong, Porcelana, 250012
- Qilu Hospital of Shandong University
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- over 18 years of age;
- body mass index (BMI) 18.5-28 kg/m2;
- having protective ileostomy after colorectal carcinoma surgery free of disease;
- with endoscopic and histological confirmation of diversion colitis;
- no oral antibiotics or probiotic within 3 months;
- having signed the informed consent.
Exclusion Criteria:
- under 18 years of age;
- a history of drug or alcohol abuse;
- clinical history and histological confirmation of inflammatory bowel disease or other gastrointestinal motility disorders with colorectal involvement;
- previous abdominal surgery;
- mental disorders;
- other serious chronic diseases, such as cardiovascular and cerebrovascular diseases, diabetes, respiratory diseases, etc;
- serious perioperative complications such as anastomotic rupture after surgery;
- oral antibiotics or probiotic within three months;
- participation in any other studies within the past 3 months;
- refusal to participate in the study.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Doble
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: preoperative stimulation of diverted colorectal segments with GABA before ileostomy closure surgery
Patients allocated to the GABA group received local preoperative enema stimulation of the diverted distal colorectal segment once daily for four consecutive days before ileostomy closure. For each session, the contents of four GNC GABA 750-mg capsules, providing 3,000 mg of labeled GABA, were dissolved in 100 mL of sterile 0.9% sodium chloride injection manufactured by Shijiazhuang No. 4 Pharmaceutical Co., Ltd. (Shijiazhuang, China), yielding a final nominal GABA concentration of 30 mg/mL. GABA was supplied as commercially available dietary-supplement-grade capsules (GNC Holdings, LLC, Pittsburgh, PA, USA). According to the manufacturer's label, each capsule contained 750 mg of gamma-aminobutyric acid; a numerical analytical purity specification was not provided by the manufacturer. The preparation was made aseptically immediately before administration and infused slowly over 10-20 minutes through a sterile 14-Ch Foley catheter connected to an infusion set. |
Foley catheter No.14 Ch connected to an infusion set was introduced through the defunctioned bowel to allow the slow infusion, for 10-20 minutes, of a solution with 3000 mg of GABA diluted in 100 ml of 0.9% physiological saline. |
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Comparador falso: control group was stimulated with 0.9% saline
Patients allocated to the sham group received 100 mL sterile 0.9% sodium chloride injection following an identical protocol, including catheter insertion, infusion route, infusion volume, infusion duration, and symptom recording, but without GABA administration. After completion of four enema sessions, all patients underwent ileostomy closure within the subsequent 24 h. |
Foley catheter No.14 Ch connected to an infusion set was introduced through the defunctioned bowel to allow the slow infusion, for 10-20 minutes, of 100 ml of 0.9% physiological saline. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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time to first flatus
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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time from the end of surgery to the first passage of flatus |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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the incidence of POI (Postoperative Ileus)
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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the incidence of POI |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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time to first passage of stool
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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time to first passage of stool |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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incidence of watery stool
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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incidence of watery stool |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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time to first liquid intake
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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time to first liquid intake |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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time to tolerance of a solid diet
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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time to tolerance of a solid diet |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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total and postoperative lengths of hospital stay
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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total and postoperative lengths of hospital stay |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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profiling of the gut microbiome
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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metagenomic sequencing of the gut microbiota. |
From date of the end of surgery until the date of discharge, assessed up to 20 days
|
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profiling of metabolome
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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metabolomic profiling of colonic lavage fluid and plasma. |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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serum biochemical measurements
Periodo de tiempo: From date of the end of surgery until the date of discharge, assessed up to 20 days
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biochemical indicators of hepatic and renal function, lipid metabolism, and glucose metabolism |
From date of the end of surgery until the date of discharge, assessed up to 20 days
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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
- Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q. GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11692-7. doi: 10.1073/pnas.1102715108. Epub 2011 Jun 27.
- Strandwitz P, Kim KH, Terekhova D, Liu JK, Sharma A, Levering J, McDonald D, Dietrich D, Ramadhar TR, Lekbua A, Mroue N, Liston C, Stewart EJ, Dubin MJ, Zengler K, Knight R, Gilbert JA, Clardy J, Lewis K. GABA-modulating bacteria of the human gut microbiota. Nat Microbiol. 2019 Mar;4(3):396-403. doi: 10.1038/s41564-018-0307-3. Epub 2018 Dec 10.
- 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.
- Bansal P, Wang S, Liu S, Xiang YY, Lu WY, Wang Q. GABA coordinates with insulin in regulating secretory function in pancreatic INS-1 beta-cells. PLoS One. 2011;6(10):e26225. doi: 10.1371/journal.pone.0026225. Epub 2011 Oct 21.
- 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.
- Wang S, Xiang YY, Zhu J, Yi F, Li J, Liu C, Lu WY. Protective roles of hepatic GABA signaling in acute liver injury of rats. Am J Physiol Gastrointest Liver Physiol. 2017 Mar 1;312(3):G208-G218. doi: 10.1152/ajpgi.00344.2016. Epub 2016 Dec 15.
- Wang S, Sui S, Liu Z, Peng C, Liu J, Luo D, Fan X, Liu C, Lu WY. Protective roles of hepatic gamma-aminobutyric acid signaling in acute ethanol exposure-induced liver injury. J Appl Toxicol. 2018 Mar;38(3):341-350. doi: 10.1002/jat.3544. Epub 2017 Oct 17.
- Beamish EL, Johnson J, Shaw EJ, Scott NA, Bhowmick A, Rigby RJ. Loop ileostomy-mediated fecal stream diversion is associated with microbial dysbiosis. Gut Microbes. 2017 Sep 3;8(5):467-478. doi: 10.1080/19490976.2017.1339003. Epub 2017 Jun 16.
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Otros números de identificación del estudio
- KYLL-202212-066-1
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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