Clinical trial NCT05004155: Twenty Four Hour Ambulatory pH & Impedance Testing: Normative Data for Indian Population
Official title: Twenty Four Hour Ambulatory pH & Impedance Testing: Normative Data for Indian Population
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Esophageal Diseases
Esophagitis
Reflux Disease
Keywords: esophageal diseases
normative data
Reflux disease
Lead sponsor: Asian Institute of Gastroenterology, India
Sponsor class: OTHER
First posted: 2021-08-13
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will enroll only healthy asymtomatic subjects, so that normative data can be generated.

Brief summary: GERD is common in Indian population and the normative data which is used to diagnose \& manage GERD and its complications are based on western data which is not validated in the Indian population. Although normative data is available for commonly used twenty-four impedance-pH parameters, their global application has limitations, stemming from use of small healthy volunteer cohorts from few countries for normative data. At present, there is no normative data for twenty-four hours impedance-pH monitoring in Indian population. The aim of this study is to obtain a new set of normal values specific for the Indian population.

Detailed description: 1. INTRODUCTION Ambulatory impedance-pH monitoring is well established in the investigation of oesophageal symptoms suspicious of gastro-oesophageal reflux disease (GERD), and may be of particular value where symptoms persist or do not improve with empiric GERD treatment trials or GERD management, or where the diagnosis of GERD is inconclusive. Although normal values are available for commonly used impedance-pH parameters, their global application has limitations, stemming from use of small healthy volunteer cohorts from one or two countries for normative data. Further, significant technical limitations in analysis exist, such as inclusion of pH drops from meals/artefacts and inconsistent rules for identification of impedance reflux events, leading to large inter-reviewer variability. Several measurement systems are used for impedance-pH monitoring worldwide. Despite regional differences in prevalence of GERD phenotypes, symptomatic profiles and GERD complications, the same impedance-pH threshold values are used to define normality by these measurement systems. It remains unclear if measurements obtained using different systems or across world regions are comparable, especially since automated analysis provided by impedance-pH systems suffers from significant overcall of reflux episodes. Accurate identification and quantification of acid and non-acid reflux episodes on impedance-pH monitoring is important for precise calculation of oesophageal acid exposure time (AET), for reflux-symptom association analysis, and for evaluation of clearance mechanisms such as the postreflux swallow induced peristaltic wave (PSPW). Both reflux episodes and PSPW need to be reliably identified and recorded, for correct calculation of the PSPW index. Baseline impedance from impedance-pH monitoring can provide a measure of oesophageal mucosal integrity. Baseline impedance during the nocturnal supine period has been shown to be higher in healthy subjects and patients with functional heartburn and lower in patients with reflux disease. We aimed to obtain a new set of normal values for impedance- pH monitoring based on consensus analysis of impedance pH studies performed using different hardware/software systems from a large worldwide cohort of healthy asymptomatic subjects.
2. RATIONALE Although normal values are available for commonly used impedance-pH parameters, their global application has limitations, stemming from use of small healthy volunteer cohorts from one or two countries for normative data. At present, there is no normative data for impedance-pH monitoring in Indian population. The aim of this study is to obtain a new set of normal values specific for the Indian population.
3. STUDY OBJECTIVES 3a. Primary objective - To establish normative data for impedance-pH monitoring in Indian population.
4. STUDY POPULATION- 50 healthy asymptomatic subjects
5. DESIGN AND DURATION OF THE STUDY- It will be a observational prospective study. The study duration will be till completion of data collection for 50 subjects.

6a. SUBJECT RECRUITMENT - Healthy volunteers

6b. RANDOMIZATION AND BLINDING- Not applicable

6c. STUDY METHODS- This observational study will be conducted among 50 patients of both sexes after obtaining ethical clearance from institutional human ethical committee. Study participants will be of the age more than 18 years. Exclusion criteria will consist of thoracic or digestive foregut surgery, alcohol consumption \>40 g/day, use of medications that alter intragastric acidity or oesophageal motility, as well as history of diabetes mellitus, neurological disorders or other chronic gastrointestinal disease.

6d. STUDY PROCEDURE- After at least 6 hours of fasting, a catheter will be placed through the nasal passage, and then swallowed into the esophagus with drinks of water. The other end of the catheter will be taped to cheek, wrapped over ear, and attached to a small data recorder that the subject will wear at waist level, held by a strap over the shoulder. Subject will be able to swallow, talk, and breathe without any difficulty during the test. Placement of the catheter will take about 10 minutes. One pH electrode will be positioned 5 cm proximal to the manometrically identified lower oesophageal sphincter (LES), and six impedance channels with their midpoint located 3, 5, 7, 9, 15 and 17 cm proximal to the LES. During the recording period, subjects will be encouraged to continue with their usual daily activities and meals. Subjects will be asked to keep a diary during the testing, including every time you eat, drink, or take medicines, and how long that lasts, when you lie down and get up, and each and every time you have a symptom of interest (like heartburn, regurgitation, cough, sore throat, etc.). Subject cannot take a shower or bath while wearing the monitor. Suject will return next day to have the catheter removed and to turn in the diary. Removing the catheter takes less than one minute. The total duration of catheter placement will be 24 hours. The equipment used will be pH monitoring catheter (Alacer, Brazil).

6e. METHODS OF ASSESSMENT- All tracings will be initially checked, and excluded if they had technical artefacts, marked oesophageal symptoms or antireflux medication intake. During the subsequent analysis process, tracings will be excluded if they fulfilled criteria for behavioural disorders (aerophagia, supragastric belching and rumination), low mean nocturnal baseline impedance (MNBI) in all impedance channels suspicious for eosinophilic oesophagitis (EoE) and hiatal hernia larger than 2 cm (in those with available HRM). All tracings will be analysed by four individuals, each with experience in reviewing \>300 impedance-pH studies annually. Reviewers will initially apply automated analysis, followed by manual review of each identified reflux episode and PSPW for accuracy, as well as manual addition of missed events identified within the time window of 3 min used to edit the reflux events detected by automated analysis, with two reviewer consensus for each retained episode. The analysis process will consist of: (1) editing of pH drops (to exclude artefacts and meal/drink induced pH drops). Slow pH drifts without impedance reflux were included for calculation of total AET but were not considered separate reflux episodes. (2) Identification of impedance reflux events and PSPW using strict pre-established criteria and (3) measurement of distal MNBI. After manual editing, the following parameters will be considered for normative data: total, upright and supine AET, number of reflux events (total, acid and non-acid), PSPW index and MNBI at 3 and 5 cm above the LES.

6f. STOPPING OR DISCONTINUATION CRITERIA- Not applicable

7. OUTCOME MEASURES 7a. Primary - To establish normative data for impedance-pH monitoring in Indian population.

There are no secondary objectives.

8. STATISTICAL ANALYSIS- Data will be expressed as median and percentile values (5th, 25th, 75th and 95th percentiles). Depending on normality of distribution, we will use either paired Student's t-test or Mann-Whitney U test for paired comparison. Likewise, we will use one way analysis of variance with Tukey test or Kruskal-Wallis, followed by Dunn's test as appropriate. Upper limit of normal will be defined as the 95th percentile of normal values. For PSPW index and MNBI thresholds, we will use the 5th and 25th percentile values. P≤0.05 will be considered statistically significant.

Eligibility criteria: Inclusion Criteria:

* Healthy individual \> 18 years of age
* Not on any acid lowering drug from at least 7 days.

Exclusion Criteria:

* Thoracic or digestive foregut surgery,
* Alcohol consumption \>40 g/day,
* Use of medications that alter intragastric acidity or oesophageal motility
* History of diabetes mellitus,
* Neurological disorders
* Chronic gastrointestinal disease
* Any subject with upper GI symptoms like pain, burning, belching, bloating, dysphagia \& aerophagia

Primary outcomes:
measure: Normative values for impedance-pH monitoring in healthy Indian population.
timeFrame: six months
Secondary outcomes:
Other outcomes:
Locations:
city: Hyderabad
country: India
facility: AIG Hospitals
state: Telangana
Study officials:
affiliation: Senior Consultant
name: Rakesh kalapala, MBBS, MD, DM
role: STUDY_DIRECTOR
affiliation: Consultant
name: Pradev Inavolu
role: PRINCIPAL_INVESTIGATOR
affiliation: Consultant
name: Hardik Rughwani
role: PRINCIPAL_INVESTIGATOR
References:
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