Clinical trial NCT04006977: Multistrain Probiotics Reduces UC Depression and Anxiety Scores
Official title: Multistrain Probiotic Product (De Simone Formulation) Reduces Depression and Anxiety Scores: a Randomized Pilot Study in Patients With Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Ulcerative Colitis
Keywords: probiotics; psychological disorder;DSF
Lead sponsor: Xijing Hospital of Digestive Diseases
Sponsor class: OTHER
Collaborators: name: MENDES SA
First posted: 2019-07-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: reduction of anxiety and depression scores
timeFrame: 0 week, 8 weeks, 12 weeks, 16 weeks
Secondary outcomes:
measure: Clinical response
timeFrame: 4 weeks, 8 weeks, 12 weeks, 16 weeks
measure: Clinical remission
timeFrame: 4 weeks, 8 weeks, 12 weeks, 16 weeks
measure: Endoscopic remission/response
timeFrame: 0 week, 16 weeks
measure: Changes in fecal-associated microbiota following probiotic therapy
timeFrame: 0 week, 16 weeks
measure: Identification of potential stressors
timeFrame: 0 weeks, 16 weeks
measure: Adverse events
timeFrame: 4 weeks, 8 weeks, 12 weeks, 16 weeks
Other outcomes:
Locations:
city: Xi'an
country: China
facility: Xijing Digestive Disease
state: Shaanxi
Study officials:
affiliation: Hospital of Digeetive Disease, Xi'an, Shaanxi, Xijing, China
name: Jie Liang, Professor
role: PRINCIPAL_INVESTIGATOR
References: