Use of Pyrvinium to Reverse Stomach Precancerous Conditions

NCT06782048 | Not Yet Recruiting Phase 2

• 1 other identifier: 2024-3680
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study is carried out to find out if a drug called pyrvinium is able to convert pre-cancerous tissue in the stomach back to healthy tissue, to lower the chances of stomach cancer. Pyrvinium is a drug that has been used for a long time to treat pinworms in children and its anti-cancer properties are currently under investigation. Tests in animals have shown that pyrvinium made unhealthy tissue healthier and stopped some cells from growing in a bad way. Based on preclinical studies, the investigators hypothesise that the proportion of samples with pre-cancerous tissue in the stomach would decrease by 50% after exposure to pyrvinium at the 6-week timepoint, with anticipated durability of the response at the one-year follow-up.

Conditions

STOMACH NEOPLASM

Keywords

Gastric Cancer; Stomach Neoplasm; Intestinal Metaplasia; Pyrvinium

Outcome Measures

Primary Outcomes (1)

• Histological Regression of GIM: Average percentage change of GIM in the antrum and corpus, as measured by histological evaluation of gastric biopsies at baseline and the study endpoint

  Baseline, 6 weeks post-treatment

Secondary Outcomes (7)

• Surface Area of GIM Involvement: Measured in real-time using AI-guided imaging technology during endoscopy

  During endoscopy at baseline, Day 7 of treatment, 6 weeks post-treatment and 1 year post-treatment

• Safety: Number of participants with treatment-related adverse events

  From Day 1 to Day 14 of treatment

• Efficacy in Patient-Derived Gastroids: Changes in phosphorylation levels of proteins in pre-cancerous gastroids derived from participants with GIM or dysplasia

  Baseline

• Efficacy in Patient-Derived Gastroids: Evaluation of growth and proliferation after pyrvinium treatment via imaging, staining and histological techniques

  Baseline

• Mechanistic Insights into Pyrvinium Action: Gene expression profiles (e.g., mucins MUC1, MUC2, MUC5AC) in biopsied gastric samples obtained during endoscopy

  Baseline, Day 7, 6 weeks post-treatment, 1 year post-treatment

Study Arms (2)

Pyrvinium

EXPERIMENTAL

Pyrvinium will be administered to participants.

Drug: Pyrvinium; Procedure: Blood biomarkers analyses; Procedure: Oesophagogastroduodenoscopy (OGD) and biopsy; Other: Gastric juice, saliva and stool collection and analyses

Placebo

PLACEBO COMPARATOR

Placebo will be administered to participants.

Drug: Placebo; Procedure: Blood biomarkers analyses; Procedure: Oesophagogastroduodenoscopy (OGD) and biopsy; Other: Gastric juice, saliva and stool collection and analyses

Interventions

Placebo DRUG

Participants will receive placebo by mouth once each day for a total of 14 days.

Placebo

Pyrvinium DRUG

Participants will receive pyrvinium (2 mg/kg/day) by mouth once each day for a total of 14 days.

Pyrvinium

Blood biomarkers analyses PROCEDURE

Up to 20ml of blood will be drawn from each participant at each study visit, with a total of 4 study visits for molecular analyses.

Placebo; Pyrvinium

Oesophagogastroduodenoscopy (OGD) and biopsy PROCEDURE

Study participant will undergo OGD with collection of gastric mucosal biopsies at the baseline visit to ascertain IM status and for molecular analyses. Study participant will undergo follow-up gastroscopy with collection of gastric mucosal biopsies at day 7 of treatment, 6 weeks post-treatment and 1 year post-treatment to assess if endpoint is reached and for molecular analyses. Gastric juice samples will be collected during each OGD.

Placebo; Pyrvinium

Gastric juice, saliva and stool collection and analyses OTHER

Gastric juice will be taken, and gastric pH will be measured at each research endoscopy. Saliva and stool will also be obtained from participants at research endoscopy for microbiome studies at the following timepoints: baseline, 6 weeks post-treatment, and 1 year post-treatment.

Placebo; Pyrvinium

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject is at least 21 years of age.
• The subject has histologically proven extensive/marked intestinal metaplasia and/or dysplasia.
• The subject is willing and able to provide signed and dated patient informed consent form indicating that he/she has been informed of all pertinent aspects of the study.

You may not qualify if:

• The subject has an active gastric cancer diagnosis.
• The subject is pregnant.
• The subject has a high-risk of bleeding complications due to anticoagulants or underlying medical condition such as bleeding disorders in whom biopsies are contraindicated.
• The subject has impaired renal function.
• The subject has impaired hepatic function.
• The subject has fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency.
• The subject has chronic bowel disease.
• The subject has any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may interfere with the interpretation of study results and in the judgement of the investigator would make the subject unsuitable for entry into the study.
• The subject is unwilling or unable to provide signed informed consent.

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• National University of Singapore: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

National University Hospital

Singapore, 122107, Singapore

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

pyrvinium; Endoscopy, Digestive System; Biopsy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Digestive System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Digestive System Surgical Procedures; Surgical Procedures, Operative; Minimally Invasive Surgical Procedures; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Specimen Handling; Investigative Techniques

Central Study Contacts

Jonathan Wei Jie Lee, MBBS, MRCP, MCI

CONTACT

+6567723951; jonathanlee@nus.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2024
• First Posted: January 17, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: January 17, 2025

Record last verified: 2024-12

Locations

SG (1)