The regulatory acceptance enables a team of gastroenterologists at Harvard’s Beth Israel Deaconess Medical Center to initiate a Phase II randomized, triple-blind, and placebo-controlled clinical trial to investigate the role of the gut microbiome in patients with Irritable Bowel Syndrome (IBS), as well as the impact of DS-01 on both intestinal cells and metabolic output of the native intestinal microbial communities.
DS-01 was developed with Dr Gregor Reid, Seed Health CSO, past-President of the International Scientific Association of Probiotics and Prebiotics (ISAPP), and former Chair of the UN-World Health Organization Expert Panel that authored the global scientific definition of probiotics.
DS-01 is described as a “broad-spectrum probiotic with 24 genetically distinct microorganisms across 12 species, including strains with novel mechanistic data that have been investigated in multiple randomized, double-blind, placebo-controlled human clinical trials”.
Commenting on the IND, Dr Reid said: “Acceptance of the IND is an exciting advancement for the field of probiotic research. This study is the first of several that will generate both mechanistic and clinical data in randomized, triple-blind, placebo-controlled interventional trials to investigate DS-01.”
Raja Dhir, co-CEO of Seed Health, told NutraIngredients-USA that Seed only has one product, and DS-01 is the same formulation as used in its Daily Synbiotic product.
IBS
IBS is thought to affect about 11% of people around the world. According to Canavan et al. (2014), total annual direct costs related to IBS were between £45.6 and £200 million in the UK and $1.35 billion in the USA.
The syndrome is characterized by a combination of chronic or recurring abdominal pain or discomfort, and symptoms range from diarrhea and constipation to bloating and distension. It is often accompanied by psychosocial distress and impaired quality of life.
While specific aspects of IBS like chronic constipation can be treated pharmacologically, treatment for many symptoms are currently limited to experimental dietary and lifestyle recommendations.
Although the underlying cause of IBS is unknown, recent studies have shown a link between IBS and an altered gut immune response, particularly as related to disruption of the intestinal microbiota. The current working hypothesis is that an abnormal microbiota drives impaired intestinal permeability and dysregulated immune responses, causing gastrointestinal distress, explained the company.
AGA guidelines
As reported earlier this year by NutraIngredients-USA, the American Gastroenterological Association’s Practice Guidelines on the Role of Probiotics in the Management of Gastrointestinal Disorders stated that the evidence is currently insufficient to make recommendations regarding the use of probiotics to treat IBS.
The guidelines called for ‘well defined clinical trials’ to establish the safety of specific formulations on clinical conditions relevant to gastroenterology
“IBS is one of the most common conditions globally, but previous research on microbiota-based interventions for IBS has been inconsistent and inconclusive,” said Dr. James Versalovic, Seed Health Advisor, Professor of Pathology and Immunology at Baylor College of Medicine, and early pioneer in the field of metagenomic medicine.
“Seed Health's upcoming interventional trial represents a new approach to studying IBS by focusing not only on gut microbiota composition, but also on the thousands of bioactive metabolites it produces.”
Study details
The upcoming study will be led by gastroenterologist Dr. Anthony Lembo, of the Division of Gastroenterology, Hepatology and Nutrition at Beth Israel Deaconess Medical Center.
The focus is on two types of IBS-C (constipation) and -M (mixed). 120 IBS patients are being recruited with the goal of having 100 finish the study, Dhir told us. Interestingly, the placebo effect in IBS studies is large, with 30-40% of IBS patients responding to placebo.
The researchers have adopted an “elegant approach” to this placebo effect, said Dhir: The study is starting with a placebo run-in meaning that all study participants will receive placebo at the start, and the really high responders will be excluded before study randomization. “This provides a more robust data set and it’s more likely that participants will have a response to the treatment,” he said.
The participants in the treatment group will receive 53 billion AFUs per day of DS-01 for 12 weeks,
The trial will assess metagenomic stability, measured through shotgun metagenomic DNA sequencing, alongside metabolic output of the gut microbiota, daily abdominal pain, daily stool consistency, IBS symptom severity, IBS adequate relief, daily abdominal discomfort, daily abdominal bloating, number of bowel movements per day, gut permeability, and overall quality of life.
Participants will also use a mobile companion application to report the day-to-day gastrointestinal symptoms and quality of life inputs, whereas previous studies have relied on often inconsistent, low-compliant manual reporting.
“The findings from this study will push the field forward regardless of the outcome,” said Dhir.