Effect of Herbal Extract Granules Combined With Probiotics on Irritable Bowel Syndrome With Diarrhea

NCT ID: NCT01342718

Last Updated: 2012-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2012-04-30

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.

Conditions

Irritable Bowel Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

GJS/Duolac7S

GJS: Real herbal extract granule/Duolac7S: Real probiotics

Group Type: EXPERIMENTAL

Herbal extract granule and probiotics

Intervention Type: DIETARY_SUPPLEMENT

The herbal extract granule, Gwakhyangjeonggisan granule, consists of 11 herbs. Ingredients: Agastachis, Perillae Folium, Angelicae Radix, Arecae Pericarpium, Hoelen, Magnoliae officinalis Cortex, Atractylis Rhizoma, Aurantii nobilis Percarpium, Pinelliae Rhizoma, Platycodi Radix, Glychrrhizae Radix. Dosage and frequency: 1 pack (3g), 3 packs per day (2 hours after morning, afternoon and evening meal)

The probiotics, Duolac7S, consist of 7 bacteria. Ingredients: Lactobacillus acidophilus, L. plantarum, L. rhamnosus, Bifidobacterium breve, B. lactis, B. longum, Streptococcus thermophilus. Dosage and frequency: 1 capsule (5✕1,000,000,000 bacteria/capsule [7✕100,000,000 viable cells/strain]), 2 capsules per day (2 hours after morning and evening meal)

GJS-P/Duolac7S

GJS-P: Placebo herbal extract granule/Duolac7S: Real probiotics

Group Type: PLACEBO_COMPARATOR

Placebo herbal extract granule and probiotics

Intervention Type: DIETARY_SUPPLEMENT

The Gwakhyangjeonggisan placebo has the same form, color and flavor as experimental intervention (Gwakhyangjeonggisan). The dosage, frequency and duration is also the same as experimental intervention (Gwakhyangjeonggisan).

The probiotics, Duolac7S, consist of 7 bacteria. Ingredients: Lactobacillus acidophilus, L. plantarum, L. rhamnosus, Bifidobacterium breve, B. lactis, B. longum, Streptococcus thermophilus. Dosage and frequency: 1 capsule (5✕1,000,000,000 bacteria/capsule [7✕100,000,000 viable cells/strain]), 2 capsules per day (2 hours after morning and evening meal)

GJS/Duolac7S-P

GJS: Real herbal extract granule/Duolac7S-P: Placebo probiotics

Group Type: PLACEBO_COMPARATOR

Herbal extract granule and placebo probiotics

Intervention Type: DIETARY_SUPPLEMENT

The herbal extract granule, Gwakhyangjeonggisan granule, consists of 11 herbs. Ingredients: Agastachis, Perillae Folium, Angelicae Radix, Arecae Pericarpium, Hoelen, Magnoliae officinalis Cortex, Atractylis Rhizoma, Aurantii nobilis Percarpium, Pinelliae Rhizoma, Platycodi Radix, Glychrrhizae Radix. Dosage and frequency: 1 pack (3g), 3 packs per day (2 hours after morning, afternoon and evening meal).

Duolac7S placebo has the same form, color and flavor as experimental intervention (Duolac7S). The dosage, frequency and duration is also the same as experimental intervention (Duolac7S).

GJS-P/Duolac7S-P

GJS-P: Placebo herbal extract granule/Duolac7S-P: Placebo probiotics

Group Type: PLACEBO_COMPARATOR

Placebo herbal extract granule and placebo probiotics

Intervention Type: DIETARY_SUPPLEMENT

The Gwakhyangjeonggisan placebo has the same form, color and flavor as experimental intervention (Gwakhyangjeonggisan). The dosage, frequency and duration is also the same as experimental intervention (Gwakhyangjeonggisan).

Duolac7S placebo has the same form, color and flavor as experimental intervention (Duolac7S). The dosage, frequency and duration is also the same as experimental intervention (Duolac7S).

Interventions

Herbal extract granule and probiotics

The herbal extract granule, Gwakhyangjeonggisan granule, consists of 11 herbs. Ingredients: Agastachis, Perillae Folium, Angelicae Radix, Arecae Pericarpium, Hoelen, Magnoliae officinalis Cortex, Atractylis Rhizoma, Aurantii nobilis Percarpium, Pinelliae Rhizoma, Platycodi Radix, Glychrrhizae Radix. Dosage and frequency: 1 pack (3g), 3 packs per day (2 hours after morning, afternoon and evening meal)

The probiotics, Duolac7S, consist of 7 bacteria. Ingredients: Lactobacillus acidophilus, L. plantarum, L. rhamnosus, Bifidobacterium breve, B. lactis, B. longum, Streptococcus thermophilus. Dosage and frequency: 1 capsule (5✕1,000,000,000 bacteria/capsule [7✕100,000,000 viable cells/strain]), 2 capsules per day (2 hours after morning and evening meal)

Intervention Type: DIETARY_SUPPLEMENT

Herbal extract granule and placebo probiotics

The herbal extract granule, Gwakhyangjeonggisan granule, consists of 11 herbs. Ingredients: Agastachis, Perillae Folium, Angelicae Radix, Arecae Pericarpium, Hoelen, Magnoliae officinalis Cortex, Atractylis Rhizoma, Aurantii nobilis Percarpium, Pinelliae Rhizoma, Platycodi Radix, Glychrrhizae Radix. Dosage and frequency: 1 pack (3g), 3 packs per day (2 hours after morning, afternoon and evening meal).

Duolac7S placebo has the same form, color and flavor as experimental intervention (Duolac7S). The dosage, frequency and duration is also the same as experimental intervention (Duolac7S).

Intervention Type: DIETARY_SUPPLEMENT

Placebo herbal extract granule and probiotics

The Gwakhyangjeonggisan placebo has the same form, color and flavor as experimental intervention (Gwakhyangjeonggisan). The dosage, frequency and duration is also the same as experimental intervention (Gwakhyangjeonggisan).

The probiotics, Duolac7S, consist of 7 bacteria. Ingredients: Lactobacillus acidophilus, L. plantarum, L. rhamnosus, Bifidobacterium breve, B. lactis, B. longum, Streptococcus thermophilus. Dosage and frequency: 1 capsule (5✕1,000,000,000 bacteria/capsule [7✕100,000,000 viable cells/strain]), 2 capsules per day (2 hours after morning and evening meal)

Intervention Type: DIETARY_SUPPLEMENT

Placebo herbal extract granule and placebo probiotics

The Gwakhyangjeonggisan placebo has the same form, color and flavor as experimental intervention (Gwakhyangjeonggisan). The dosage, frequency and duration is also the same as experimental intervention (Gwakhyangjeonggisan).

Duolac7S placebo has the same form, color and flavor as experimental intervention (Duolac7S). The dosage, frequency and duration is also the same as experimental intervention (Duolac7S).

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Gwakhyangjeonggisan granule and Duolac7S; Gwakhyangjeonggisan granule and placebo Duolac7S; Placebo Gwakhyangjeonggisan granule and Duolac7S; Placebo Gwakhyangjeonggisan granule and placebo Duolac7S

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyunghee University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Seok-Jae Ko

Resident, Department of Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jae-Woo Park, KMD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea

Locations

Kyung Hee University Hospital at Gangdong

Seoul, Gangdong-gu, South Korea

Countries

South Korea

References

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.

Reference Type: DERIVED

PMID: 21978382 (View on PubMed)

Related Links

http://www.khnmc.or.kr/

This is the URL of the site in which the clinical trial will be conducted.

Other Identifiers

KHNMC-OH-IRB 2010-011

Identifier Type: -

Identifier Source: org_study_id