Effect of Herbal Extract Granules Combined With Probiotics on Irritable Bowel Syndrome With Diarrhea
Condition: Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Syndrome; Diarrhea
Study type: Interventional

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.
    

Intervention name(s): Herbal extract granule and probiotics; Herbal extract granule and placebo probiotics; Placebo herbal extract granule and probiotics; Placebo herbal extract granule and placebo probiotics
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): 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); 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).; 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); 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).
Other intervention name(s): Gwakhyangjeonggisan granule and Duolac7S; Gwakhyangjeonggisan granule and placebo Duolac7S; Placebo Gwakhyangjeonggisan granule and Duolac7S; Placebo Gwakhyangjeonggisan granule and placebo Duolac7S
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Irritable bowel syndrome; Herbal medicine; Probiotics