Clinical trial NCT01342718: Effect of Herbal Extract Granules Combined With Probiotics on Irritable Bowel Syndrome With Diarrhea
Official title: Effect of Herbal Extract Granules Combined With Probiotics on Irritable Bowel Syndrome With Diarrhea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Irritable Bowel Syndrome
Keywords: Irritable bowel syndrome
Herbal medicine
Probiotics
Lead sponsor: Kyunghee University Medical Center
Sponsor class: OTHER
First posted: 2011-04-27
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aims of this study are to investigate the effect of famous herbal formula extract and probiotics on irritable bowel syndrome with diarrhea, and to determine whether these two experimental items affect intestinal permeability and the composition of intestinal microbiota.

Detailed description: Irritable bowel syndrome (IBS), a common chronic gastrointestinal disorder characterized by abdominal pain and alteration of bowel habits in the absence of structural abnormality, has a prevalence of approximately 15% in western populations1,2. Patients with IBS can be classified by their predominant bowel habits: diarrhea-predominant IBS (D-IBS), constipation-predominant IBS, or IBS with alternating bowel movements3. Although smooth-muscle relaxants, bulking agents, and anti-diarrheal agents are commonly used as conventional IBS treatments, many IBS patients turn to alternative treatments because of the lack of therapeutic advantages of these treatments4. Therefore, the development of a new therapy is necessary for IBS patients.

Gwakhyangjeonggisan (GJS; Kkako-shoki-san in Kampo Medicine; Huoxiang-zhengqi-san in Traditional Chinese Medicine), which was recorded originally in the famous ancient herbal formula literature "Formularies of the Bureau of people's Welfare Pharmacies", consists of 13 common crude herbs. GJS contains the chemical ingredients naringin, hesperidin, thymol, honokiol and magnolol5. GJS has been shown to protect intestinal barrier function6, contract the colonic muscle7, and regulate infectious diarrhea8 in vivo. In traditional Korean medicine, this herbal formula has long been used for relieving abdominal pain, diarrhea, and vomiting as an over-the-counter or prescribed medicine9-11. However, there have been no clinical trials to investigate the efficacy of GJS in IBS.

Probiotics are defined as viable microorganisms, which confer potential health benefits on the host when taken in proper amounts12. They are easily available, do not require a prescription, and are administered extensively for the relief of abdominal symptoms13. According to a recent systematic review and meta-analysis study, probiotics caused a modest improvement in the overall IBS symptoms14. The rationale for using probiotics for IBS is based on the assumption that they modify the composition of the intestinal microflora15 and regulate intestinal permeability by modulating the epithelial tight junctions16. Duolac7S (DUO), a probiotic mixture, contains 7 bacterial species including Bifidobacterium, Lactobacillus, and Streptococcus. Each of these bacterial species is reportedly beneficial for IBS17. DUO has been approved by the Korean Food and Drug Administration for restoring the ecological balance of intestinal microflora and improving intestinal symptoms18. Although DUO has been widely used as an over-the-counter product for IBS-related symptoms, no clinical trials have investigated the efficacy of DUO on IBS.

Recently, several herbal formulas and probiotics have been simultaneously administered to IBS patients for relieving abdominal symptoms19. In addition to lack of clinical evidence for the use of GJS or DUO, the efficacy of their combined treatment for IBS has not been elucidated. Thus, there is a need to evaluate the safety and efficacy of administration of GJS, DUO, or a combination therapy as a frequently used treatment for IBS. In the current trial, we identified the safety and efficacy of GJS, DUO, or a combination therapy on D-IBS by evaluating IBS symptoms and quality of life. To investigate their mechanisms in humans, intestinal permeability and composition of intestinal microbiota were assessed.

Eligibility criteria: Inclusion Criteria:

1. Age of 18 - 75, with a elementary-school diploma or higher, must be literate
2. One who meet Rome Ⅲ IBS-D criteria
3. One who agree on not taking other therapies during experimental period
4. During the past 5 yrs, no history of organic lesion proven by colonoscopy
5. One who agree on consent form

Exclusion Criteria:

1. Patients who have abdominal operation in the past(exception: appendectomy, caesarean section, tubal ligation, laparoscopic cholecystectomy, hysterectomy and abdominal wall hernia repair)
2. No history of non-functional bowel disease(cholangitis, pancreatitis, enteritis, ulcer, bleeding, cancer, etc.)
3. Before participation clinical trial, one who took over-the-count medication affecting GI motility
4. One who takes antibiotics during run-in period (2 wks)
5. One who takes probiotics within 2 wks before experiment
6. Pregnant woman
7. One who disagree on the consent form

Primary outcomes:
measure: Adequate relief (AR) of IBS pain & discomfort
timeFrame: Weekly (during run-period [2 wks], administarion period [8 wks] and follow-up period [2 wks])
measure: Proportion of responders
timeFrame: Once in each period (run-period [2 wks], administarion period [8 wks] and follow-up period [2 wks])
Secondary outcomes:
measure: Daily assessment of bowel function scores
timeFrame: Daily (during run-period [2 wks], administarion period [8 wks] and follow-up period [2 wks])
measure: Daily assessment of severity of individual symptoms related to defecation
timeFrame: Daily (during run-period [2 wks], administarion period [8 wks] and follow-up period [2 wks])
measure: Changes on population of intestinal microbes
timeFrame: Two times in administration period (0 and 8 wks)
measure: Intestinal permeability test
timeFrame: Two times in administration period (0 and 8 wks)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
state: Gangdong-gu
Study officials:
affiliation: Department of Internal Medicine, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea
name: Jae-Woo Park, KMD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ko SJ, Ryu B, Kim J, Hong BG, Yeo I, Lee BJ, Lee JM, Park JW. Effect of herbal extract granules combined with probiotic mixture on irritable bowel syndrome with diarrhea: study protocol for a randomized controlled trial. Trials. 2011 Oct 6;12:219. doi: 10.1186/1745-6215-12-219.