Early Detection of Barrett's Esophagus in Participants With Reflux Symptoms in Primary Care (ELECTRONIC)

Early Detection of Barrett's Esophagus and Esophageal Cancer: Accuracy and Acceptability of a Novel Screening Strategy in Primary Care

In the Netherlands, the incidence of esophageal adenocarcinoma (EAC) is increasing. In addition, EAC has a dismal prognosis. Therefore, screening for Barrett's Esophagus (BE) has stimulated interest. Although BE is a known precursor of EAC, a minority of patients with EAC are known with a previous diagnosis of BE. A non-invasive screening tool, such as breath testing, could select patients at risk for BE, after which unsedated transnasal endoscopy (uTNE) can confirm or exclude the diagnosis. The objective is to determine the accuracy and acceptability of a non-invasive screening strategy i.e. breath testing followed by uTNE for BE and EAC.

Study Overview

• Status: Completed
• Conditions: Esophageal Cancer; Barrett Esophagus
• Intervention / Treatment: Diagnostic test: Breath test (eNose) followed by uTNE.

Detailed Description

The ongoing increasing incidence of esophageal adenocarcinoma (EAC) in the Netherlands during the last few decades and the still dismal prognosis has stimulated interest in screening for Barrett's esophagus (BE). Although BE is a known precursor of EAC, a minority of patients with EAC (<10%) are known with a previous diagnosis of BE, and hence, most cases of BE are undiagnosed. Screening programs to detect BE followed by endoscopic surveillance and treatment of dysplasia or early neoplasia seem able to reduce the incidence of EAC and improve survival. A non-invasive screening tool, such as breath testing, could select patients at risk for BE, after which unsedated transnasal endoscopy (uTNE) can confirm or exclude the diagnosis. uTNE offers the possibility of a more acceptable and accurate endoscopic assessment of the esophagus with almost neglectable risks and lower costs compared to conventional endoscopy. The objective is to determine the accuracy and acceptability of a non-invasive screening strategy i.e. breath testing followed by uTNE for BE and EAC.

• Study Type: Interventional
• Enrollment (Actual): 449
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lotte J. Huibertse; Phone Number: +31 0650155752; Email: Lotte.Huibertse@radboudumc.nl
• Study Contact Backup: Name: Yonne Peters, Drs.; Phone Number: +31 0615956464; Email: Y.Peters@radboudumc.nl

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboud University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient aged 50 to 75 years;
• Recorded diagnosis of reflux symptoms >90 days OR
• Recorded prescriptions for acid suppressant therapy for this indication for at least 1 year in the past 5 years
• Written informed consent.

Exclusion Criteria:

• Upper endoscopy in the previous 5 years;
• A current or previous diagnosis and/or treatment of any type of malignancy (not including basal-cell skin cancer (BCC) and squamous-cell skin cancer (SCC)) within the last five years;
• Already known with a diagnosis of Barrett's esophagus or gastro-esophageal cancer;
• Any argument provided by a patient's own general practitioner not to include the patient;
• Comorbidities precluding transnasal endoscopy (e.g. inability to discontinue oral anticoagulants, history of recurrent epistaxis, allergy to lidocaine derivatives).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Breath test (eNose) followed by uTNE.; All participants will receive the breath test with the eNose in the general practice, followed by the uTNE in the hospital.	Diagnostic test: Breath test (eNose) followed by uTNE.; All participants will receive the breath test with the eNose in the general practice, followed by the uTNE in the hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Predictive Value (PPV) of the eNose for detecting confirmed BE	PPV of the eNose for detecting confirmed BE with the diagnosis made by transnasal endoscopy and upper endoscopy as the reference standard in primary care.	16 weeks after breath test (eNose)
Negative Predictive Value (NPV) of the eNose for detecting confirmed BE	NPV of the eNose for detecting confirmed BE with the diagnosis made by transnasal endoscopy and upper endoscopy as the reference standard in primary care.	16 weeks after breath test (eNose)
Sensitivity of the eNose for detecting confirmed BE	Sensitivity of the eNose for detecting confirmed BE with the diagnosis made by transnasal endoscopy and upper endoscopy as the reference standard in primary care.	16 weeks after breath test (eNose)
Specificity of the eNose for detecting confirmed BE	Specificity of the eNose for detecting confirmed BE with the diagnosis made by transnasal endoscopy and upper endoscopy as the reference standard in primary care.	16 weeks after breath test (eNose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient acceptability (discomfort and overall experience) of the eNose measured on a NPRS.	Patient acceptability consists of two questions regarding discomfort and overall experience of the eNose. Discomfort is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'none' and 10 being 'severe'. Overall experience is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'the worst experience', 5 being 'neither pleasant nor unpleasant' and 10 being 'the best experience'.	Directly after breath test (eNose)
Patient acceptability (discomfort and overall experience) of uTNE measured on a NPRS.	Patient acceptability consists of two questions regarding discomfort and overall experience of uTNE. Discomfort is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'none' and 10 being 'severe'. Overall experience is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'the worst experience', 5 being 'neither pleasant nor unpleasant' and 10 being 'the best experience'.	Directly after uTNE
Patient acceptability (discomfort and overall experience) of conventional endoscopy (if applicable) measured on a NPRS.	Patient acceptability consists of two questions regarding discomfort and overall experience of conventional endoscopy. Discomfort is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'none' and 10 being 'severe'. Overall experience is measured on a Numeric Pain Rating Scale (NPRS) with 0 being 'the worst experience', 5 being 'neither pleasant nor unpleasant' and 10 being 'the best experience'.	Directly after conventional endoscopy
Willingness to undergo repeat eNose procedure	Willingness to undergo repeat procedure consists of one question with answer options 'Yes' and 'No'.	Directly after breath test (eNose)
Willingness to undergo repeat uTNE procedure	Willingness to undergo repeat procedure consists of one question with answer options 'Yes' and 'No'.	Directly after uTNE
Willingness to undergo repeat conventional endoscopy	Willingness to undergo repeat procedure consists of one question with answer options 'Yes' and 'No'.	Directly after conventional endoscopy
Cancer worry (CWS-8)	The Cancer Worry Scale (CWS-8) is used to measure cancer worry. Scores are ranging from 8 to 32, and higher scores indicate more cancer worry.	At baseline, 7 days after eNose, 7 days after uTNE, 7 days after conventional endoscopy (if applicable), 30 days after eNose, 30 days after uTNE, 30 days after conventional endoscopy (if applicable), 90 days after last study procedure.
Anxiety (STAI-6)	The State-Trait Anxiety Inventory (STAI-6) is used to measure anxiety. Scores are ranging from 6 to 24, and higher scores indicate more anxiety.	At baseline, 7 days after eNose, 7 days after uTNE, 7 days after conventional endoscopy (if applicable), 30 days after eNose, 30 days after uTNE, 30 days after conventional endoscopy (if applicable), 90 days after last study procedure.
Impact of event (IES-15)	The Impact of Event Scale (IES-15) is used to measure impact of event. Scores are ranging from 0 to 75, and higher scores indicate more impact of event.	7 days after eNose, 7 days after uTNE, 7 days after conventional endoscopy (if applicable), 30 days after eNose, 30 days after uTNE, 30 days after conventional endoscopy (if applicable), 90 days after last study procedure.
Rate of successful evaluation by uTNE	The rate of successful intubation and complete evaluation will be measured.	1 week after the last participant undergoes uTNE.
Rate of successful evaluation by breath test (eNose)	The rate of successful intubation and complete evaluation will be measured.	1 week after the last participant undergoes breath test (eNose).
Safety of uTNE based on reported Adverse Events.	The safety will be measured based on reported Adverse Events.	1 week after the last participant undergoes uTNE.
Safety of eNose based on reported Adverse Events.	The safety will be measured based on reported Adverse Events.	1 week after the last participant undergoes breath test (eNose).

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Dutch Digestive Diseases Foundation
• Investigators: Principal Investigator: Peter D. Siersema, Prof.dr., Radboud University Medical Center Nijmegen

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Actual): March 11, 2024
• Study Completion (Actual): March 11, 2024

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: December 4, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Primary care; Screening; General practice; Esophageal Cancer; Barrett Esophagus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Precancerous Conditions; Esophageal Neoplasms; Barrett Esophagus
• Other Study ID Numbers: 110769

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No