The Role of Probiotics in Improving Quality of Life in Women With Functional Constipation: Randomized Double-blind Controlled Trial
Phase: PHASE2
Conditions: Constipation - Functional
Sponsor: Fakultas Kedokteran Universitas Indonesia

 
 
 
STUDY PROTOCOL 
(29 January 2018) 
 
 
The Role of Probiotics in Improving Quality of Life in Women with 
Functional Constipation: Randomized Double-blind Controlled 
Trial 
 
 
 
 
      Principal Investigator 
 
: Prof. Dr. dr. Murdani Abdullah, SpPD-KGEH 
 
  
Co-Investigators  
 
: dr. Hasan Maulahela, SpPD 
 
 
  dr. Amanda Pitarini Utari, SpPD 
 
 
  Pratiwi Dyah Kusumo, S.Si., M.Biomed 
 
 
  Prof. dr. Amin Soebandrio, Ph.D, Sp.MK 
 
 
  Prof. Dr. dr. Dadang Makmun, SpPD-KGEH 
 
This study is supported by 
: United States Agency for International 
Development (USAID) through the Sustainable 
Higher Education Research Alliance (SHERA) 
Program for Universitas Indonesia’s Scientific 
Modelling, Application, Research and Training 
for City-Centered Innovation and Technology 
(SMART CITY) Project 
 
Grant  
 
: #AID-497-A-1600004 
 
Sub Grant 
 
: #IIE-00000078-UI-1 
 
 
 
 
 
 

I. 
Introduction 
Functional constipation has a negative impact on patients’ quality of life, 
including in the urban community. Reduction of quality of life consists of 
social aspect such as psychological disorders, lethargy, anxiety, and also 
economical aspect such as decreased productivity. One of functional 
constipation pathophysiology is the intestinal-brain communication disorder 
(Gut Brain Axis) influenced by hormonal, serotonin production gene 
variations so as to give a large psychological impact on the sufferer. The 
negative impact of functional constipation which occurs in 2.5-19% of the 
world population is especially greater in women. While probiotics have 
previously been linked with positive results on various gastrointestinal 
disorders, there has never been a study investigating probiotics positive 
impact on quality of life in urban women with functional constipation. Thus, 
this study aims to investigate probiotics effect in improving quality of life in 
urban women with functional constipation. 
 
II. 
Study Objective 
To investigate the relationship between administration of probiotics and 
improvement in quality of life in women with functional constipation. 
 
III. 
Study Design 
• Parallel group design, randomized, probiotic versus placebo for 21 days. 
• Block randomization using permutation blocks of size 8. 
• Double-blinded evaluation. 
 
IV. 
Methodology 
Patients 
Inclusion Criteria 
• Females aged 18 to 60 years 
• Being declared healthy based on initial examination and the Structured 
Interview Questionnaire (SIQ) 
• Having the symptoms and signs of functional constipation refer to ROME-
IV criteria 
• Able to communicate well 
• Able to consume 1 bottle of fermented milk each day for three weeks 
• Not using antibiotic no later than one week before supplementation 
 
Exclusion Criteria 
• Diagnosed with functional bowel disorder 
• Using anesthesia at least 4 weeks before treatment 
• Having a serious pathological disorder (carcinoma) 
• During healing phase of acute gastrointestinal disorders at least 4 weeks 
before treatment 
• Having severe heart disease 
• Taking chronic medications such as antidepressants or analgesics 
 

Study Intervention 
Drug Presentation 
• Test drug: fermented milk containing probiotic Lactobacillus plantarum 
IS-10506. 
• Comparator: fermented milk containing placebo. 
Drug Administration 
• Each subject receives 1 bottle of fermented milk, to be consumed once 
daily at the same hour for a duration of 21 days. 
• Fermented milk will be stored in a freezer (-16oC) into frozen condition, 
and must be left at room temperature for several hours before drunk in 
cold-liquid condition. 
Drug Supply 
• Fermented milk containing probiotic and placebo will be supplied by PT 
Ultra Jaya. 
 
Concomitant Medication 
None 
 
Primary Endpoint (by blinded evaluator) 
Improvement in quality of life, assessed with PAC-QOL© (Patient 
Assessment of Constipation – Quality of Life) questionnaire. 
 
Sample Size 
The minimum sample size is 62, plus a 10% dropout prediction: 70. 
 
Procedure 
All patients will be collected from Puskesmas Petamburan Jakarta.  
 
After signing the informed consent, the subjects will be assessed for eligibility 
using inclusion and exclusion criteria by medical staff of Division of 
Gastroenterology, Department of Internal Medicine, Faculty of Medicine 
Universitas Indonesia – Cipto Mangunkusumo Hospital in collaboration with 
Puskesmas Petamburan Jakarta. The remaining subjects will be randomly 
allocated into two groups: probiotic group and placebo group, and will be 
assessed on their initial quality of life with PAC-QOL© (Patient Assessment 
of Constipation – Quality of Life) questionnaire by trained personnel. 
 
Each subject will receive 1 bottle of fermented milk containing either 
probiotic or placebo to be consumed once daily at the same hour for a duration 
of 21 days. 
 
After 3 weeks, the subjects will return to the study site and will be reassessed 
on their final quality of life with PAC-QOL© (Patient Assessment of 
Constipation – Quality of Life) questionnaire by trained personnel. 
 
 

V. 
Data Management and Statistical Analysis 
 
Efficacy Analysis 
Statistical analysis between probiotic versus placebo at 21 days after 
intervention: 
• PAC-QOL© score: use paired T test 
 
VI. 
Ethical Committee Approval 
Approval from the Ethics Committee of the Faculty of Medicine, Universitas 
Indonesia must be obtained before starting the trial. 
 
VII. 
References 
1. Drossman DA, Hasler WL. Rome IV - Functional GI disorders: Disorders 
of gut-brain interaction. Gastroenterology. 2016;150(6):1257–61. 
http://dx.doi.org/10.1053/j.gastro.2016.02.032  
2. Schoenfeld PS. Advances in IBS 2016 : A Review of Current and 
Emerging Data. Gastroenterol Hepatol (N Y). 2017;12(8):S3–11.  
3. Lacy BE, Mearin F, Chang L, Chey WD, Lembo AJ, Simren M, et al. 
Bowel disorders. Gastroenterology. 2016;150(6):1393–1407e5. 
http://dx.doi.org/10.1053/j.gastro.2016.02.031  
4. Stephanie NS, Mawe GM. Non-conventional features of peripheral 
serotonin signalling — the gut and beyond. Nature Reviews 
Gastroenterology & Hepatology.2017:51  
5. Zhu L, Liu W, Alkhouri R, Baker RD, Bard JE, Quigley EM, et al. 
Structural changes in the gut microbiome of constipated patients. Physiol 
Genomics. 2014;46(18):679–86. 
doi:10.1152/physiolgenomics.00082.2014.  
6. Schippa S, Conte M. Dysbiotic Events in Gut Microbiota: Impact on 
Human Health. Nutrients 2014, 6, 5786-5805; doi:10.3390/nu6125786.  
7. National consensus on the management of constipation in indonesia 
2010.Indonesian Society of Gastroenterology (ISG). Acta Med Indones. 
2011 Oct;43(4):267- 74.(abstrak)  
8. Wald A, Mueller-lissner S, Kamm MA, Hinkel U, Richters E, Schujit C, 
Mandel KG. Survey of laxative use by adults with self-defined 
constipation in South America and Asia: a comparison of six countries. 
Aliment Pharmacol Ther . 2010;31: 274–284 doi:10.1111/j.1365-
2036.2009.04169.x