The Influence of Obesity to Esophageal Reflux Severity Measured by pH-Metri Impedans on Gastroesophageal Reflux Disease Patients
Conditions: Disorder of Upper Esophageal Sphincter
Sponsor: Indonesia University

RESEARCH PROTOCOL 
 
 
 
 
 
IMPACT OF OBESITY ON SEVERITY OF ESOPHAGEAL REFLUX IN 
GASTROESOPHAGEAL REFLUX DISEASE MEASURED BY PH-
METER IMPEDANCE 
 
 
 
 
 
 
 
INVESTIGATORS: 
Principal 
: S C Rijal  
Others 
: Prof. Ari Fahrial Syam, SpPD, K-GEH, Prof. dr. Marcellus 
Simadibrata, SpPD, K-GEH, PhD, dr. Arif Mansjoer, Sp.PD 
 
 
 
 
 
 
 
 
 
FACULTY OF MEDICINE 
UNIVERSITY OF INDONESIA 
 

I. BACKGROUND 
 
Gastroesophageal reflux disease (GERD), a prevalent communal health problem, is defined as 
a condition wherein the contents of the stomach are refluxed into the esophagus, resulting in 
symptoms and/or complications [1]. Although rarely the cause of death, GERD is associated 
with increased morbidity and negatively affects the quality of life [2]. Epidemiological studies 
show that the prevalence of GERD in Western countries is approximately 20%, with a 4% 
annual increase in prevalence [1,3]. Based on the studies in several Asian countries, its 
prevalence in Asia appears to be lower than that in the United States or Europe, but the 
prevalence has nonetheless increased in the past few decades [4-6]. In a hospital-based study, 
Syam et al. (2003) reported an increase in the prevalence of esophagitis from 5.7% in 1997 to 
25.18% in 2002 [7]. Lelosutan et al. (2001) reported that GERD was diagnosed in 22.8% of 
127 patients, based on upper GI endoscopy [8]. Recent data from 2016 also showed the 
prevalence of GERD among medical doctors to be 27.4% in Indonesian doctors [9].  
The National Health and Nutrition Examination Survey (USA) reported that among 20–74-
year-old adults, the prevalence of obesity increased from 15.0% in 1976–1980 to 32.9% in 
2003–2004. It is estimated that by 2020, 77.6% of men will be overweight, and 40.2% will be 
obese; in addition, 71.1% of women will be overweight, and 43.3% will be obese [9]. Although 
the association between GERD and obesity remains unclear, they are believed to be positively 
related [10]. Syam et al. reported that obese patients have a higher risk of GERD, with the 
causative factors being higher dietary intake, decreased physical activity, and genetic 
predisposition. However, to the best of our knowledge, no studies have specifically examined 
the relationship between obesity and severity of esophageal reflux in GERD patients [11].  
Currently, the GERD questionnaire (GerdQ) is used as a screening tool for GERD, with a 
specificity and specificity of 64.6% and 71.4%, respectively [12]. In Indonesia, GERD is 
diagnosed based on symptoms assessed using the GerdQ and upper gastrointestinal endoscopy. 
Unfortunately, because approximately 70% of GERD patients do not show esophageal damage 
during upper gastrointestinal endoscopy, the diagnosis of GERD requires methods that provide 
greater precision, one such method being the multichannel intraluminal impedance pH-meter 
(MII-pH) test, an esophageal manometric method that detects the incidence of reflux for 24 h 
and can be used to measure the strength of esophageal acidity; the latter represents severity of 
esophageal reflux. MII-pH results are expressed as the DeMeester or pH composite score 
[12,13]. 

II. OBJECTIVE AND HYPOTHESIS 
 
A. General Objective 
 
To ascertain if there is an association between obesity and severity of esophageal reflux, GERD 
must be diagnosed with greater precision and accuracy. 
B. Specific Objective 
 
1. To measure the acid exposure time obese patients and normal BMI patients. 
2. To record the number of observed hiatal hernia in obese patients and normal BMI 
patients. 
3. To record the number of erosive esophagitis in obese patients and normal BMI 
patients. 
C. Hypothesis 
 
1. Obese patients had higher DeMeester score and acid exposure time compared to 
normal BMI patient. 
2. Obese patient had a higher number of observed hiatal hernia. 
3. Obese patient had a higher number of observed erosive esophagitis. 
 

 
III. METHODS 
 
A. Study Design 
 
This study is a cross sectional study. 
 
B. Time and Place 
 
A cross-sectional study involving 98 GERD patients was conducted between January and 
October 2017 at the Department of Internal Medicine, Cipto Mangunkusumo Hospital 
(Jakarta, Indonesia). 
C. Study Population 
 
1. Targeted population: Adult patients with GERD 
 
2. Sample: Adult patients with GERD in in Cipto Mangunkusumo Hospital, Jakarta. 
3. Inclusion Criteria 
 
• Adults, aged 18–60 years; 
• Normal BMI (18.5–23.5 kg/m2) or obese BMI ( 25 kg/m2); the BMI cut-off was based 
on the criteria for the Asia-Pacific population 
• Fulfill GERD criteria assessed using GerdQ 
• Gave undergone upper gastrointestinal tract endoscopy 
• Willing to participate by providing written informed consent. 
 
4. Exclusion Criteria 
 
• Severe blood clotting disorders, severe heart disease, persistent asthma, decompensated 
liver cirrhosis, and chronic kidney disease. 
• Prescribed benzodiazepine drugs, tricyclic antidepressants, dihydropyridine calcium 
channel blockers, adrenergic alpha inhibitors, beta blockers, or nonsteroidal anti-
inflammatory drugs. 
• Diagnosed with psychological disorders.

5. Drop Out Criteria: Patients who have signed the informed consent but wish to stop 
participating before completed the study. 
D. Study Procedure 
 
Patients diagnosed with Barrett’s esophagus, peptic ulcers, or severe NSAID gastropathy; 
those suffering from hematemesis, melena, gastric cancer, esophageal cancer, pharyngeal 
obstruction, or upper esophagus on endoscopic examination; those in whom MII-pH meter 
could not be attached; uncooperative patients; and those unable to understand or follow 
instructions were also excluded from this study. 
From 110 subjects who met the inclusion criteria, we excluded 12 subjects due to the above 
reasons. All 98 eligible subjects (59 female and 39 male) were recruited, provided 
anamnesis, and underwent a physical examination that included measurement of their 
weight and height. 
The GerdQ was administered to all subjects, and those with a score of ≥ 8 points were 
diagnosed as having GERD. All patients with diagnosed GERD underwent upper 
gastrointestinal endoscopy, during which hiatal hernia and erosive esophagitis were also 
evaluated. The patients with diagnosed GERD also underwent MII-pH examination for 24 
h for the quantification of the DeMeester score. 
 
MMI-pH 
MII-pH test was performed after an 8-h fast and after being PPI-free for seven days. The MII-
pH system comprises a portable data storage unit and a catheter with one pH electrode and eight 
impedance electrodes at positions 3, 5, 7, 9, 15, and 17 cm from the tip. The electrode was placed 
5 cm above the LES boundary, as determined by manometry. The patients were asked to press 
an event marker button on the data storage unit when they experienced symptoms and 
subsequently record information on the timing of symptoms, start and finish time, and changes 
in body position (lying or upright) in a diary. They were also required to at least eat three meals 
a day and were asked to maintain normal activity. Data were recorded on a 256 MB compact 
flash card, downloaded onto a computer for analysis using semi-automated software, and 
manually verified.

E. Ethics 
 
The study protocol was approved by Health Research Ethics Committee, Faculty of Medicine, 
Universitas Indonesia-Cipto Mangunkusumo Hospital (No. 719/UN2.F1/ETIK/2017). 

IV. STUDY ANALYTICAL PLAN 
 
The data were analyzed using the STATA program (StataCorp). Categorical variables are presented as 
frequency and percentage, whereas numerical variables are presented as mean (with standard deviation) for 
normally distributed data. The median (with minimum and maximum range) is used for non- normally 
distributed data. Dichotomous categorical variables were analyzed using the chi-square test. Normality was 
evaluated using ..., and non-normal data was subjected to bivariate analysis using the Mann–Whitney U-test to 
compare the DeMeester score between the two groups. Statistical significance was set at p < 0.05, with 95% 
confidential interval (CI)..

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