Multistrain Probiotics Reduces UC Depression and Anxiety Scores

Multistrain Probiotic Product (De Simone Formulation) Reduces Depression and Anxiety Scores: a Randomized Pilot Study in Patients With Ulcerative Colitis

This pilot study aims to evaluate the effect of a 16-week duration of multistrain probiotic product (De Simone Fomulation (DSF), previously known as VSL#3 and now available as Vivomixx in EU and Visbiome in USA to reduce anxiety and depression scores in mild to moderate active UC. It has been known that gut microbiota is associated with IBD and mental health. In addition, IBD patients complicated with psychiatric disorders are rising more and more attention. Further, a recent study "Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome" was published in Gastroenterology in 2017, thus we wonder if DSF have an effect on the depression/anxiety in patients with UC）A total of 60 patients will be randomly allocated into two groups, group A will receive standard medical therapy plus placebo (4 sachets/day,), and group B will receive standard medical therapy plus DSF (each sachet containing 450 billion CFU, eight bacterial strains 4 sachets/day) for 16 weeks. The primary endpoint is the reduction of anxiety and depression scores after treatment (at 8 weeks and 16 weeks) using hospital anxiety and depression scale (HADS). The secondary endpoints including clinical response after 8-week and 16-week treatment (measured by a ≥3-point reduction in a Simple Clinical Colitis Activity Index (SCCAI) score at 16 weeks), and clinical remission (defined as SCCAI score ≤5 at 8 weeks and 16 weeks). Changes in fecal-associated microbiota by 16S ribosomal RNA sequencing and metabolomics using company service following probiotics therapy (at 16 weeks) were also assessed, stratified by both change in SCCAI score following probiotics therapy and randomization. Adverse events were evaluated at week 8 and 16 weeks by patient survey

Study Overview

• Status: Unknown
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: a multistrain probiotic product (DSF)

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jie Liang, Professor; Phone Number: 86-029-85771535; Email: liangjie@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Xijing Digestive Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female patients aged ≥18
2. Patients with mild-to-moderately active UC (defined as a SCCAI score of ≥ 5 and < 12 and a colonoscopy will be performed to confirm the classification)
3. Patients with psychological dysfunction at screening based on hospital anxiety and depression scale (HADS), defined as HAD-A or HAD-D score ≥ 8
4. Signed Informed Consent obtained

Exclusion Criteria:

1. Severe ulcerative colitis (SCCAI score ≥ 12) or toxic dilatation of the colon
2. Prior bowel (either intestine or colon) resection surgery
3. Patients with any other disease or condition which might interfere with their participation in the trial, including significant hepatic, renal, endocrine, respiratory, neurologic, immune deficiency, cardiovascular, malignant diseases, bleeding disorders, autoimmune diseases and schizophrenia.

4. Take the following treatment:

   1. Antibiotics within 4 weeks prior to screening
   2. Oral steroids within the past 4 weeks before screening
   3. Acetyl-salicylic acid ≤100 mg/day as anti-platelet therapy or NSAIDs within 4 weeks prior screening
   4. Consecutive consumption of probiotics in 4 weeks prior to enrollment
   5. Topical or oral steroids within the past 4 weeks before screening
5. Patients requiring hospitalization or imminent need for surgery
6. Significant hepatic function abnormalities, defined as the values of serum ALT or AST ≥twice of the upper limit of normal value
7. Women who are planning or actual pregnancy or lactating during study period
8. Alcohol addiction (>40 g of alcohol/day，equivalent to >1 L of beer/day, 0.5 L of wine/day)
9. Patients with a history of a psychiatric condition other than anxiety or depression, use of opioids, antidepressants or anxiolytics in regular doses, illicit drug consumption
10. Patients participating or having participated in another clinical study 30 days prior to screening
11. Patients with one or more of the diseases: bacillary dysentery, amebic dysentery, chronic schistosomiasis, intestinal tuberculosis and Crohn's disease
12. Patients who are unwilling to comply with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1: placebo plus standard therapy; placebo plus standard therapy	Dietary supplement: Placebo; In Arm 1, participants will receive standard medical therapy plus the placebo.
Experimental: Arm 2: DSF plus standard therapy; DSF (4 sachets/day) plus standard therapy	Dietary supplement: a multistrain probiotic product (DSF); In Arm 2, participants will receive standard medical therapy plus the multistrain probiotics (DSF), 4 sachets per day.; Other Names: De Simone Fomulation (DSF), previously known as VSL#3 and now available as Vivomixx in EU and Visbiome in USA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction of anxiety and depression scores	reduction of anxiety and depression scores (with points as standard units) using HADS at 8 weeks and 16 weeks after randomized treatment	0 week, 8 weeks, 12 weeks, 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	measured by a ≥1.5(3) points reduction in Simple Clinical Colitis Activity Index score at week 8 and 16	4 weeks, 8 weeks, 12 weeks, 16 weeks
Clinical remission	measured by Simple Clinical Colitis Activity Index score ≤5(2) points at week 8 and 16	4 weeks, 8 weeks, 12 weeks, 16 weeks
Endoscopic remission/response	measured by a Mayo endoscopic subscore of <1 point, or at least a 1 point reduction from baseline in the endoscopy subscore at week 16	0 week, 16 weeks
Changes in fecal-associated microbiota following probiotic therapy	Changes in fecal-associated microbiota using16S ribosomal RNA sequencing and changes in the metabolomic profile of the feces following probiotic therapy (at baseline and 16 weeks) will be assessed, stratified by both change in Simple Clinical Colitis Activity Index score following probiotic therapy and randomization.	0 week, 16 weeks
Identification of potential stressors	Participants will be asked to complete a modified practical and family problem list to identify 13 potential stressors.	0 weeks, 16 weeks
Adverse events	Adverse events were assessed at week 8 and 16 by patient survey.	4 weeks, 8 weeks, 12 weeks, 16 weeks

Collaborators and Investigators

• Sponsor: Xijing Hospital of Digestive Diseases
• Collaborators: MENDES SA
• Investigators: Principal Investigator: Jie Liang, Professor, Hospital of Digeetive Disease, Xi'an, Shaanxi, Xijing, China

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2019
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): May 1, 2020

Study Registration Dates

• First Submitted: July 1, 2019
• First Submitted That Met QC Criteria: July 1, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): September 12, 2019
• Last Update Submitted That Met QC Criteria: September 10, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: probiotics; psychological disorder;DSF
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: XijingHDD-UC-Probiotics

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No