GMPA Versus PPI for Gastric Protection and aGVHD Risk

NCT07791849 | Recruiting

• 1 other identifier: GP-aGVHD-001
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to observe whether different gastric protection strategies affect the incidence of acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Proton pump inhibitors (PPIs) are routinely used for gastric protection during transplantation, but their prolonged use may suppress gastric acid, alter gut microbiota, and potentially increase the risk of aGVHD. Teprenone, a gastric mucosal protective agent (GMPA), enhances mucosal defense mechanisms including promoting mucus secretion, increasing gastric mucosal blood flow, and facilitating epithelial cell repair, without affecting gastric acid secretion, and may therefore preserve microbial diversity and modify aGVHD risk. This study compares two strategies: continuous PPI use versus switching from PPIs to teprenone after transplantation. The main questions this study aims to answer are:

• Does switching from PPIs to teprenone after transplantation reduce the cumulative incidence of aGVHD within +100 days post-transplantation compared with continuous PPI use?
• What adverse events do participants experience with teprenone versus continuous PPI therapy?
• Does teprenone therapy provide better preservation of gut microbial diversity and lower rates of gastrointestinal and infectious complications compared with continuous PPI use? In this prospective, randomized, parallel-controlled, single-center trial, approximately 198 patients undergoing allo-HSCT will be enrolled and assigned in a 1:1 ratio using a central randomization system. The experimental group (teprenone group) will receive standard-dose PPIs (esomeprazole, 40 mg/d, intravenous/oral) during conditioning and switch to teprenone (50 mg tid, orally) after transplantation through day +100. The control group (PPI group) will receive continuous standard-dose PPIs from conditioning through day +100. Probiotic use is prohibited from conditioning through day +100 in both groups. All other anti-infective, GVHD prophylaxis, and supportive care regimens are identical between the two groups. The primary endpoint of this study is the cumulative incidence of aGVHD within +100 days post-transplantation. Secondary endpoints include grade II-IV and grade III-IV aGVHD, lower gastrointestinal aGVHD, steroid-refractory aGVHD, gut and salivary microbiome dynamics (α-diversity, β-diversity, and specific taxa at pre-conditioning, day 0, day +14, and day +28), plasma biomarkers related to intestinal barrier integrity, systemic inflammation, and immune regulation , infectious and gastrointestinal complications (febrile neutropenia, diarrhea, C. difficile infection, bacteremia, EBV/CMV reactivation, upper GI bleeding, reflux), and 1-year survival outcomes (non-relapse mortality, overall survival, GVHD-free/relapse-free survival). During the study, participants will:
• Receive the assigned gastric protection regimen (teprenone or PPI) according to randomization
• Undergo regular assessments for safety and efficacy monitoring, including aGVHD surveillance and infection screening
• Provide fecal and saliva samples at pre-conditioning, day 0, day +14, and day +28 post-transplantation for microbiome analysis
• Provide peripheral blood samples at pre-conditioning, day 0, day +14, and day +28 post-transplantation for exploratory analysis
• Be followed for up to 1 year post-transplantation

Conditions

Hematopoietic Stem Cell Transplantation (HSCT); aGVHD; Infection; Mortality; Microbiome

Keywords

hematopoietic stem cell transplantation; PPI; GMPA; acute graft versus host disease; microbiome

Outcome Measures

Primary Outcomes (1)

• Incidence of acute graft-versus-host disease (aGVHD) post-transplantation

  From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first

Secondary Outcomes (15)

• Incidence of grade II-IV acute graft-versus-host disease (aGVHD)

  From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first

• Incidence of grade III-IV acute graft-versus-host disease (aGVHD)

  From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first

• Incidence of lower gastrointestinal aGVHD

  From Day 0 to Day +100 post-transplantation, or until death or loss to follow-up, whichever came first

• Oral microbiome diversity and composition

  At pre-conditioning, Day +0, Day +14, and Day +28 post-transplantation

• Fecal microbiome diversity and composition

  At pre-conditioning, Day +0, Day +14, and Day +28 post-transplantation

Study Arms (2)

GMPA group

EXPERIMENTAL

Participants in this arm will receive standard-dose proton pump inhibitor (PPI) during the conditioning phase. After transplantation, they will switch to teprenone, a gastric mucosal protective agent, at a dose of 50 mg three times daily (tid), administered orally, from the day of stem cell infusion through day +100 post-transplantation.

Drug: Teprenone

PPI Group

PLACEBO COMPARATOR

Participants in this arm will receive continuous standard-dose proton pump inhibitor (PPI) therapy with esomeprazole at 40 mg daily, administered either intravenously or orally, from the start of conditioning through day +100 post-transplantation.

Drug: Esomeprazole

Interventions

Teprenone DRUG

Teprenone acts by enhancing gastric mucosal defense mechanisms, including promoting mucus secretion, increasing gastric mucosal blood flow, and facilitating epithelial cell repair, without affecting gastric acid secretion. The switch from PPI to teprenone is intended to maintain gastric protection while potentially preserving gut microbial diversity and reducing the risk of acute graft-versus-host disease (aGVHD).

GMPA group

Esomeprazole DRUG

Continuous PPI use suppresses gastric acid secretion throughout the peri-transplantation period, which may alter gut microbiota composition and potentially influence aGVHD risk.

PPI Group

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 12-70 years;
• First allogeneic haploidentical HSCT for hematological malignancy;
• Treated with a standardized myeloablative conditioning and GVHD prophylaxis regimen;
• ECOG performance status ≤2 prior to transplant;
• Written informed consent obtained.

You may not qualify if:

• Pre-existing conditions requiring continuous PPI therapy prior to transplant, including severe reflux esophagitis, Zollinger-Ellison syndrome, active peptic ulcer with bleeding, or long-term use of dual antiplatelet agents or oral anticoagulants;
• Known active, untreated Helicobacter pylori infection prior to transplant;
• Active infectious enteritis or Clostridioides difficile infection prior to transplant;
• Use of systemic broad-spectrum antibiotics within 7 days prior to transplant;
• Use of probiotics within 14 days prior to transplant;
• Planned total enteral nutrition or oral glutamine supplementation during the study period;
• Planned parenteral nutrition for ≥7 consecutive days;
• Inability to provide saliva or stool samples for collection;
• Pregnant or lactating women;
• History of significant neurological or psychiatric disorders (e.g., epilepsy, dementia) that may interfere with study participation;
• Life expectancy \<3 months or severe end-organ dysfunction;
• Any other condition that, in the investigator's judgment, may compromise patient safety, compliance, or the validity of study results.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (1)

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, 310003, China

RECRUITING

Related Publications (13)

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  PMID: 38987594 BACKGROUND

• Stein-Thoeringer CK, Nichols KB, Lazrak A, Docampo MD, Slingerland AE, Slingerland JB, Clurman AG, Armijo G, Gomes ALC, Shono Y, Staffas A, Burgos da Silva M, Devlin SM, Markey KA, Bajic D, Pinedo R, Tsakmaklis A, Littmann ER, Pastore A, Taur Y, Monette S, Arcila ME, Pickard AJ, Maloy M, Wright RJ, Amoretti LA, Fontana E, Pham D, Jamal MA, Weber D, Sung AD, Hashimoto D, Scheid C, Xavier JB, Messina JA, Romero K, Lew M, Bush A, Bohannon L, Hayasaka K, Hasegawa Y, Vehreschild MJGT, Cross JR, Ponce DM, Perales MA, Giralt SA, Jenq RR, Teshima T, Holler E, Chao NJ, Pamer EG, Peled JU, van den Brink MRM. Lactose drives Enterococcus expansion to promote graft-versus-host disease. Science. 2019 Nov 29;366(6469):1143-1149. doi: 10.1126/science.aax3760.

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• Hayase E, Hayase T, Jamal MA, Miyama T, Chang CC, Ortega MR, Ahmed SS, Karmouch JL, Sanchez CA, Brown AN, El-Himri RK, Flores II, McDaniel LK, Pham D, Halsey T, Frenk AC, Chapa VA, Heckel BE, Jin Y, Tsai WB, Prasad R, Tan L, Veillon L, Ajami NJ, Wargo JA, Galloway-Pena J, Shelburne S, Chemaly RF, Davey L, Glowacki RWP, Liu C, Rondon G, Alousi AM, Molldrem JJ, Champlin RE, Shpall EJ, Valdivia RH, Martens EC, Lorenzi PL, Jenq RR. Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease. Cell. 2022 Sep 29;185(20):3705-3719.e14. doi: 10.1016/j.cell.2022.09.007.

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  PMID: 38184001 BACKGROUND

MeSH Terms

Conditions

Infections

Interventions

geranylgeranylacetone; Esomeprazole

Intervention Hierarchy (Ancestors)

Omeprazole; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Fei Gao

CONTACT

+86 19857035073; gf0906@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Director, Bone Marrow Transplantation Center, the First Affiliated Hospital, School of Medicine, Zhejiang University

Study Record Dates

• First Submitted: August 22, 2026
• First Posted: August 28, 2026
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): September 15, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 28, 2026

Record last verified: 2026-08

Locations

CN (1)