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.
調査の概要
状態
条件
研究の種類
入学 (実際)
段階
- フェーズ 3
連絡先と場所
研究場所
-
-
Shandong
-
Jinan、Shandong、中国、250012
- Qilu Hospital of Shandong University
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：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. |
|
偽コンパレータ：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. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
time to first flatus
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
the incidence of POI (Postoperative Ileus)
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
the incidence of POI |
From date of the end of surgery until the date of discharge, assessed up to 20 days
|
|
time to first passage of stool
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
time to first passage of stool |
From date of the end of surgery until the date of discharge, assessed up to 20 days
|
|
incidence of watery stool
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
incidence of watery stool |
From date of the end of surgery until the date of discharge, assessed up to 20 days
|
|
time to first liquid intake
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
time to first liquid intake |
From date of the end of surgery until the date of discharge, assessed up to 20 days
|
|
time to tolerance of a solid diet
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
time to tolerance of a solid diet |
From date of the end of surgery until the date of discharge, assessed up to 20 days
|
|
total and postoperative lengths of hospital stay
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
total and postoperative lengths of hospital stay |
From date of the end of surgery until the date of discharge, assessed up to 20 days
|
|
profiling of the gut microbiome
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
metagenomic sequencing of the gut microbiota. |
From date of the end of surgery until the date of discharge, assessed up to 20 days
|
|
profiling of metabolome
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
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
|
|
serum biochemical measurements
時間枠：From date of the end of surgery until the date of discharge, assessed up to 20 days
|
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
|
協力者と研究者
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- KYLL-202212-066-1
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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