Pilot Study of Salivary Bile Acids and Pepsin as Predictive Biomarkers of Reflux Disease After Sleeve Gastrectomy

NCT07607067 | Not Yet Recruiting

• 1 other identifier: 86/25
• Study Type: observational
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this observational study is to learn whether bile acids and pepsin in saliva can help identify adults at higher risk of developing reflux-related esophageal disease after sleeve gastrectomy, including Los Angeles grade B-D erosive esophagitis and Barrett's esophagus. The study will include adults undergoing sleeve gastrectomy as part of their regular clinical care. Participants will be evaluated before and after surgery and will serve as their own comparison group over time. The main questions it aims to answer are: Are saliva bile acids and pepsin linked to Los Angeles grade B-D erosive esophagitis or Barrett's esophagus after sleeve gastrectomy? How do saliva bile acids and pepsin change before and after sleeve gastrectomy? Can saliva bile acids and pepsin become useful biomarkers for detecting reflux-related esophageal disease after sleeve gastrectomy? Are saliva biomarker levels linked to reflux symptoms and endoscopy results after surgery? Researchers will compare saliva biomarker levels before and after surgery and between participants with and without reflux-related esophageal disease. Participants will: Provide saliva samples before surgery and at 12 and 36 months after surgery Provide fasting and post-meal saliva samples Undergo routine postoperative clinical follow-up and upper gastrointestinal endoscopy Complete reflux symptom questionnaires during follow-up The study will also explore whether saliva biomarkers could help select participants for follow-up endoscopy after sleeve gastrectomy.

Conditions

Sleeve Gastrectomy; Saliva Collection; Reflux Disease, Gastro-Esophageal; Reflux Esophagitis (RE); Barrett Esophagus

Keywords

sleeve gastrectomy; bile acid reflux; salivary biomarkers; erosive esophagitis; Barrett Esophagus

Outcome Measures

Primary Outcomes (1)

• Association between salivary bile acid and pepsin concentrations and reflux-related esophageal disease after sleeve gastrectomy

  Association between total and specific salivary bile acid concentrations as well as pepsin and the presence of Los Angeles grade B-D erosive esophagitis and/or Barrett's esophagus detected on upper gastrointestinal endoscopy.

  12 and 36 months after sleeve gastrectomy

Secondary Outcomes (1)

• Total salivary bile acid concentration before and after sleeve gastrectomy

  Baseline before surgery, 12 months, and 36 months after sleeve gastrectomy

Other Outcomes (4)

• Profile of individual salivary bile acids and pepsin before and after sleeve gastrectomy

  Baseline before surgery, 12 months, and 36 months after sleeve gastrectomy

• Endoscopic reflux-related esophageal disease after sleeve gastrectomy

  12 and 36 months after sleeve gastrectomy

• Severity of gastroesophageal reflux symptoms after sleeve gastrectomy

  12 and 36 months after sleeve gastrectomy

Study Arms (1)

Sleeve gastrectomy cohort

Adults undergoing sleeve gastrectomy as part of routine clinical care who are prospectively evaluated before and after surgery with salivary biomarker analysis, symptom assessment, and routine postoperative endoscopic follow-up.

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults with severe obesity undergoing primary sleeve gastrectomy as part of routine clinical care at participating bariatric centers, without previous conclusive reflux-related esophageal disease on preoperative upper gastrointestinal endoscopy. Participants will be prospectively evaluated before and after surgery with saliva biomarker analysis, reflux symptom assessment, and routine postoperative endoscopic follow-up.

You may qualify if:

• Adults aged 18 years or older undergoing sleeve gastrectomy at a participating center.
• Indication for obesity treatment with sleeve gastrectomy according to the 2022 ASMBS-IFSO consensus criteria, with a maximum body mass index (BMI) of 50 kg/m².
• Approved for sleeve gastrectomy by the obesity multidisciplinary committee.
• Ability and willingness to provide informed consent for biological sample collection and analysis.
• Ability to understand and comply with scheduled follow-up visits.

You may not qualify if:

• According to Lyon 2.0 criteria, participants with previous evidence of conclusive reflux disease, including Los Angeles grade B, C, or D esophagitis, peptic stricture, or Barrett's esophagus diagnosed before surgery.
• Bariatric procedures other than sleeve gastrectomy, including Roux-en-Y gastric bypass or revisional bariatric surgery.
• History of other preexisting esophageal diseases.
• Previous esophageal surgery.
• Active cholestatic hepatobiliary disease or treatment with bile acid sequestrants, ursodeoxycholic acid, or medications that significantly alter bile acid metabolism at the time of saliva sampling or within one month before sample collection.
• Acute infection or systemic antibiotic treatment within four weeks before saliva sample collection.
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• Hospital de Mataró: lead

Related Publications (15)

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• Quante M, Bhagat G, Abrams JA, Marache F, Good P, Lee MD, Lee Y, Friedman R, Asfaha S, Dubeykovskaya Z, Mahmood U, Figueiredo JL, Kitajewski J, Shawber C, Lightdale CJ, Rustgi AK, Wang TC. Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell. 2012 Jan 17;21(1):36-51. doi: 10.1016/j.ccr.2011.12.004.

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• Quante M, Graham TA, Jansen M. Insights Into the Pathophysiology of Esophageal Adenocarcinoma. Gastroenterology. 2018 Jan;154(2):406-420. doi: 10.1053/j.gastro.2017.09.046. Epub 2017 Oct 14.

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• Perez N, Chambert K, Ribadeneira M, Currie MG, Chen Y, Kessler MM. Differential Bile Acid Detection in Refractory GERD Patient Saliva Using a Simple and Sensitive Liquid Chromatography Tandem Mass Spectrometry Approach. J Clin Gastroenterol. 2022 Mar 1;56(3):218-223. doi: 10.1097/MCG.0000000000001525.

  PMID: 33731598 BACKGROUND

• Kumar A, Gwalani P, Iyer PG, Wang KK, Falk GW, Ginsberg GG, Lightdale CJ, Del Portillo A, Lagana SM, Li Y, Li H, Genkinger J, Jin Z, Rustgi AK, Wang TC, Wang HH, Quante M, Abrams JA. Shifts in Serum Bile Acid Profiles Associated With Barrett's Esophagus and Stages of Progression to Esophageal Adenocarcinoma. Clin Transl Gastroenterol. 2024 Oct 1;15(10):e1. doi: 10.14309/ctg.0000000000000762.

  PMID: 39166758 BACKGROUND

• Kauer WK, Peters JH, DeMeester TR, Feussner H, Ireland AP, Stein HJ, Siewert RJ. Composition and concentration of bile acid reflux into the esophagus of patients with gastroesophageal reflux disease. Surgery. 1997 Nov;122(5):874-81. doi: 10.1016/s0039-6060(97)90327-5.

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• Kang HJ, Noh JK, Lee MK, Woo SR, Park JM, Lee YC, Ko SG, Eun YG. Changes of Pepsin Concentration in Saliva Sample According to Storage Period. J Voice. 2025 May;39(3):855.e7-855.e10. doi: 10.1016/j.jvoice.2022.12.010. Epub 2022 Dec 30.

  PMID: 36588013 BACKGROUND

• Gan J, Chan YK, Segaran DC, Kovalik JP, Eng A, Lee PC, Tan J, Lim CH. Pepsin in saliva for the diagnosis of erosive esophagitis post-sleeve gastrectomy: a prospective observational study. Surg Endosc. 2023 Aug;37(8):5816-5824. doi: 10.1007/s00464-023-10050-9. Epub 2023 Apr 13.

  PMID: 37055666 BACKGROUND

• Elkassem S. Gastroesophageal Reflux Disease, Esophagitis, and Barrett's Esophagus 3 to 4 Years Post Sleeve Gastrectomy. Obes Surg. 2021 Dec;31(12):5148-5155. doi: 10.1007/s11695-021-05688-0. Epub 2021 Oct 2.

  PMID: 34599728 BACKGROUND

• Dosedelova V, Lastovickova M, Konecny S, Dolina J, Kuban P. Optimization of saliva sampling methods for analysis of bile acids by UHPLC-MS. J Chromatogr A. 2024 Nov 8;1736:465354. doi: 10.1016/j.chroma.2024.465354. Epub 2024 Sep 7.

  PMID: 39276415 BACKGROUND

• Kauer WK, Peters JH, DeMeester TR, Ireland AP, Bremner CG, Hagen JA. Mixed reflux of gastric and duodenal juices is more harmful to the esophagus than gastric juice alone. The need for surgical therapy re-emphasized. Ann Surg. 1995 Oct;222(4):525-31; discussion 531-3. doi: 10.1097/00000658-199522240-00010.

  PMID: 7574932 BACKGROUND

• Dosedelova V, Lastovickova M, Ayala-Cabrera JF, Dolina J, Konecny S, Schmitz OJ, Kuban P. Quantification and identification of bile acids in saliva by liquid chromatography-mass spectrometry: Possible non-invasive diagnostics of Barrett's esophagus? J Chromatogr A. 2022 Aug 2;1676:463287. doi: 10.1016/j.chroma.2022.463287. Epub 2022 Jun 27.

  PMID: 35793575 BACKGROUND

• Chandan S, Khan SR, Deliwala SS, Dahiya DS, Mohan BP, Ramai D, Saghir SM, Dhindsa BS, Kassab LL, Facciorusso A, Nandipati K, Yang D, Adler DG. Risk of De Novo Barrett's Esophagus Post Sleeve Gastrectomy: A Systematic Review and Meta-Analysis of Studies With Long-Term Follow-Up. Clin Gastroenterol Hepatol. 2025 Jan;23(1):33-44.e10. doi: 10.1016/j.cgh.2024.06.041. Epub 2024 Jul 25.

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• Champion G, Richter JE, Vaezi MF, Singh S, Alexander R. Duodenogastroesophageal reflux: relationship to pH and importance in Barrett's esophagus. Gastroenterology. 1994 Sep;107(3):747-54. doi: 10.1016/0016-5085(94)90123-6.

  PMID: 8076761 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Saliva

MeSH Terms

Conditions

Gastroesophageal Reflux; Esophagitis, Peptic; Barrett Esophagus

Condition Hierarchy (Ancestors)

Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Esophagitis; Gastroenteritis; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases; Precancerous Conditions; Neoplasms

Study Officials

• Esther Mans Muntwyler, MD, PhD

  Hospital Universitari de Mataró, Consorci Sanitari del Maresme

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Esther Mans Muntwyler, MD, PhD

CONTACT

+34 937417700; emans@csdm.cat

Cristina Ribera, General surgery resident

CONTACT

cribera@csdm.cat

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: General Surgeon Specialized in Bariatric and Upper Gastrointestinal Surgery

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: May 26, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: May 26, 2026

Record last verified: 2026-05