SH-DS01 on Fecal Metagenomic Stability
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|ClinicalTrials.gov Identifier: NCT04598295|
Recruitment Status : Recruiting
First Posted : October 22, 2020
Last Update Posted : November 3, 2020
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder that generates a significant health care burden and is the most commonly diagnosed gastrointestinal condition. Nearly 12% of all patients in the United States seek medical care in primary care practice for IBS and it accounts for 3.1 million ambulatory care visits and 5.9 million prescriptions annually.
The pathophysiology of IBS is distinctly broad compared to other gastrointestinal conditions and includes abnormalities involving motility, visceral sensation, brain-gut interaction, and distress. Though patients with IBS often have a heterogeneous symptom profile, the predominant theme is the presence of abdominal pain or discomfort that is usually relieved by defecation. Host factors such as genetics, immune function, and psychological status, as well as environmental factors such as stress, recent infection, or treatment with antibiotics, could predispose to the development of chronic IBS symptoms. Due to a myriad of contributing factors, a single cause of IBS remains enigmatic. Despite the urgent need to develop better therapies, the high range of placebo response has made clinical trials challenging, ranging from 16.0 to 71.4% with a population-weighted average of 40.2%.
Recent studies have also shown alterations in gut immune response, and a disrupted intestinal and colonic microbiome in association with IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses, which increase epithelial permeability, activate nociceptive sensory pathways, and dysregulate the enteric nervous system. Targeting the microbiota and gastrointestinal tract with live organisms is a promising approach, yet previous trials have yielded limited success due to empiric strain selection, small population size, and inadequate trial design to control for a high placebo response.
This protocol aims to assess the impact of a multi-strain consortia of 24 commensal organisms across 12 species with extensive strain-specific in vivo data, assessing a range of gastrointestinal symptoms without negatively altering the naive gut microbiota. High-throughput shotgun DNA sequencing will provide opportunity for '-omics'-based analyses of the gut microbiota, which can be augmented by the metabolite profiles resulting from total microbial activity in the gut. Since many of these metabolites are bioeffector molecules acting upon the host, such analysis can provide a direct measure of the consequences of microbial activity in the gut and provide a novel integrated data set for patients with IBS. Recruited subjects will also use a smart-phone application to report day to day gastrointestinal symptoms, a patient-centric hallmark of this chronic gut condition.
Probiotics are live microorganisms with a vast array of therapeutic potential for gastrointestinal disease. Several probiotics strains have shown beneficial outcomes in constipation-predominant IBS (IBS-C) patients, especially as an adjunct to conventional treatment. However, a number of controversial issues regarding the roles of probiotics in pathogenesis of IBS-C remain to be clarified, including precise mechanism of action.
This protocol aims to assess the impact of a mix of 24-beneficial strains on individual gastrointestinal symptoms specifically in a cohort of subjects with IBS-C or IBS-M.
|Condition or disease||Intervention/treatment||Phase|
|Irritable Bowel Syndrome||Drug: DS-01||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Randomized, Double Blind, Placebo-controlled Study to Evaluate the Impact of a Multi-strain Synbiotic on Fecal Metagenomic Stability, Gut Barrier Integrity, and Metabolic Output of the Gut Microbiota|
|Actual Study Start Date :||October 20, 2020|
|Estimated Primary Completion Date :||September 30, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: microbial consortia (DS-01)
DS-01 is a rationally defined microbial consortia consisting of 24 strains across 12 species, with polyphenolic and phenolic prebiotic bioactive compounds. Participants will be instructed to take 2 capsules daily for the duration of the trial.
Other Name: SEED synbiotic
Placebo Comparator: placebo
Placebo capsules for DS-01 will contain rice flour matched for color and texture in an identical outer capsule shell. Participants will be instructed to take 2 capsules daily for the duration of the trial.
Other Name: SEED synbiotic
- Maintenance or increase of diversity within the DS-01 treatment group [baseline-Day 84] [ Time Frame: 12 weeks ]Microbiota composition will be identified through fecal samples for total genomic DNA extraction in participants supplemented with DS-01 or placebo. Metagenomic sequencing will yield a total observable species count and maintenance will be defined as a change in total observed species less than or equal to 20% as compared to the total observed species count at baseline.
- Percentage of responders [ Time Frame: 12 weeks ]Participants displaying a change in metagenomic signatures resulting in increased representation from baseline of Bifidobacterium longum, or Prevotella intermedia or Bacteroides helcogenes or Akkermansia muciniphila or decreased representation of Blautia hansenii in subjects with IBS-C receiving DS-01 as greater than placebo treated subjects.
- Percentage of responders [ Time Frame: 12 weeks ]Participants displaying a change in metagenomic signatures resulting in an increased representation from baseline of Alistipes finegoldii or Faecalibacterium prausnitzii or Akkermansia muciniphila or decreased representation from baseline of Blautia obeum in subjects with IBS-M receiving DS-01 greater than placebo treated subjects.
- Improvement by ≥ 15% in one or more individual IBS symptoms: abdominal pain, bloating, bowel movement difficulty, or stool consistency. [ Time Frame: 12 weeks ]Self-reported in a Symptom Tracker app to track disease progression in real-time
- Abdominal pain responder [ Time Frame: 12 weeks ]Percentage of responders in the intervention group who report a ≥ 20% reduction in average daily worst abdominal pain scores compared to placebo.
- CSBM Responder [ Time Frame: 12 weeks ]Percentage of responders in subjects with IBS-C receiving DS-01 who report an increase from baseline of 1 complete spontaneous bowel movement (CSBM) per week for at least 6 weeks compared to placebo
- Global Improvement in IBS [ Time Frame: 12 weeks ]Measured with one question with 7 possible answers: (1) much worse, (2) moderately worse, (3) slightly worse, (4) unchanged, (5) slightly better, (6) moderately better, or (7) much better.
- Adequate Relief [ Time Frame: 12 weeks ]A higher proportion of subjects in the DS-01 intervention group with Adequate Relief of Global IBS Symptoms for ≥ 30% in the intervention duration compared to the placebo group
- VSI responder [ Time Frame: 12 weeks ]A higher proportion of subjects with improvement ≥ 30% in Visceral Sensitivity Index score in the DS-01 intervention group compared to the placebo group.
- Exploratory endpoint 1 [ Time Frame: 12 weeks ]Increase in tryptamine, SCFA, and hypoxanthine production in IBS-C, changes in serine protease, LPS, or calprotectin in the DS-01 intervention group compared to the placebo group.
- Exploratory endpoint 2 [ Time Frame: 12 weeks ]Change in plasma intestinal fatty acid binding protein (I-FABP), zonulin, LPS-binding protein, soluble CD14, cytokines
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04598295
|Contact: Vivian Cheng, MS, MPHfirstname.lastname@example.org|
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Vivian Cheng 617-667-0682 email@example.com|
|Principal Investigator: Anthony Lembo, MD|
|Principal Investigator:||Anthony J Lembo, MD||Beth Israel Deaconess Medical Center|