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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Barrett Esophagus, Esophageal Cancer

Intervention / Treatment
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* Diagnostic Test: Breath test (eNose) followed by uTNE.


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: The study design is a multi-site prospective cohort study in eight general practices. All participants will receive the breath test with the eNose in the general practice, followed by the uTNE in the hospital.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Breath test (eNose) followed by uTNE.<br>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.<br>* All participants will receive the breath test with the eNose in the general practice, followed by the uTNE in the hospital.<br>|

What is the study measuring?
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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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Barrett Esophagus, Esophageal Cancer, Primary care, General practice, Screening