A Specific Probiotic in thE MOdulation of Gut Microbiota of patieNts With Mild-to-modErate Ulcerative Colitis

Официальное название

A. M in thE MOdulation of Gut Microbiota of patieNts With Mild-to-modErate Ulcerative Colitis: a Pilot,Phase 2A, Single-arm, Interventional Study

Обзор

Probiotics are live microorganisms that provide health benefits when consumed in sufficient amounts. Traditional probiotics, mainly from the Lactobacillus and Bifidobacterium genera, originate from fermented foods or the human gut and are widely used in supplements. Although considered safe and easy to produce, they are not specifically designed to treat diseases, and no official health claims have been approved by EFSA. Advances in microbiome research have led to the discovery of Next-Generation Probiotics (NGPs), which are newly identified gut microbes associated with health and offer promising therapeutic potential despite lacking a long history of safe use.

Подробное описание

The concept of probiotics dates back to 1907, when Elie Metchnikoff observed that elderly Bulgarian populations consuming fermented dairy products, such as yogurt rich in lactic acid bacteria (LAB), appeared to have increased longevity. This observation formed the basis for the development of traditional probiotics.

Traditional probiotics are defined as live microorganisms that confer a health benefit when administered in adequate amounts. These microbes are typically derived from fermented foods or the human gastrointestinal tract. Most belong to a limited number of well-characterized genera, particularly Lactobacillus and Bifidobacterium. Certain strains of these bacteria are recognized as safe and have been granted Qualified Presumption of Safety (QPS) status by the European Food Safety Authority (EFSA). In addition, they are technologically robust, meaning they can be easily cultivated and mass-produced for industrial applications.

Despite their popularity and widespread use in dietary supplements and functional foods, traditional probiotics are not specifically developed as treatments for diseases. Their mechanisms of action include modulation of gut microbiota, enhancement of the gut barrier, and interaction with the immune system. However, most supporting evidence comes from laboratory (in vitro), animal, or ex vivo studies rather than strong clinical trials. As a result, EFSA has evaluated more than 400 probiotic-related claims but has not approved any specific health claims due to insufficient conclusive evidence.

In recent years, advances in microbiota and microbiome research-particularly through metagenomics and microbial profiling-have significantly expanded our understanding of the gut ecosystem. It is now well established that dysbiosis, or imbalance in gut microbiota composition, is associated with a wide range of diseases, including metabolic, immune, and inflammatory disorders.

These scientific developments have led to the identification of new microorganisms that are associated with healthy individuals rather than traditional dietary sources. These microbes are classified as Next-Generation Probiotics (NGPs) or Live Biotherapeutic Products (LBPs). Unlike traditional probiotics, NGPs are not restricted to classical genera and do not have a long history of safe human use. Instead, they are often identified through comparative studies analyzing differences between healthy and diseased microbiomes.

NGPs represent a promising new frontier in microbiota-based therapies, as they may be specifically selected or engineered to target particular diseases or health conditions. A growing number of potentially beneficial species have been identified, opening new opportunities for precision medicine and personalized interventions based on gut microbiota composition.

Вмешательства

• Диагностический тест For a bipsies
  For the collection of a few additional biopsies
• Пищевая добавка rectal administration
  rectal administration of a specific probiotic

Первичные конечные точки

• Evaluate the effect of rectal administered a specific probiotic in Rectal mucosal healing [Срок оценки: 1 year]

Вторичные конечные точки (3)

• Evaluate the tolerability of rectal a specific probiotic in Rectal Mucosal healing [Срок оценки: 1 year]
• Evaluate the quality of life [Срок оценки: 1 year]
• evaluate the feasibility of a specific probiotic [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Men or women 18 to 80 years of age at the time of consent
• Previous diagnosis of ulcerative colitis, based on available endoscopic and histopathologic report, at least 3 months before screening
• Mild-to-moderate disease activity based on Modified Mayo Score that should be between 4 and 6 with an endoscopic subscore >1 based on endoscopic evaluation performed during screening phase
• Subjects are permitted to receive a concomitant therapeutic dose of the following IPs: Corticosteroids (≤20 mg/day of prednisone equivalents) at stable dose for at least 2 weeks before screening and mesalazine or other 5-ASA (including salazopyrin) at stable dose for at least 4 weeks before screening
• Ability to provide a written informed consent and to be compliant with the schedule of protocol assessments.

Критерии исключения

• concomitant immunosuppressive therapy, including but not limited to thiopurines, methotrexate, anti-TNFalfas, anti-integrins and anti-IL12/23 or JAK inhibitors. Biological therapies should be stopped at least 8 weeks before baseline, except for ustekinumab which should be stopped for at least 12 weeks before baseline, small molecules agent should be discontinued 5 elimination half-lives within baseline. Patients that have been previously treated with ≥ 2 advanced/biological drugs (even if belonging to the same class) will be excluded.
• Intolerance to topical therapy (enemas)
• Allergy to A. muciniphila or any other component of the IP
• Crohn's disease or inflammatory bowel disease unclassified (IBD-U)
• Subject who received IV/intramuscular corticosteroids within 14 days prior to Screening or during the Screening period.
• Subject who received topical therapy (i.e., enema or suppository of aminosalicylates / corticosteroids) within 14 days prior to Screening or during the Screening period.
• Subject who received fecal microbial transplantation within 3 months prior to Baseline.
• Subjects with the following chronic or active infections:

• Active, chronic, or recurrent infection that based on the Investigator's clinical assessment makes the subject unsuitable candidate for the study
• Infection with C. difficile, intestinal pathogen bacteria, intestinal parasites as identified during Screening as per clinical practice,
• Are infected with human immunodeficiency virus (HIV),
• Subject who has any condition including any physical, psychological, or psychiatric condition, which in the opinion of the Investigator, would compromise the safety of the subject or the quality of the data and renders the subject an unsuitable candidate for the study.
• Pregnancy and breastfeeding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Италия · 1 центр

• Fondazione Policlinico Universitario Agostino Gemelli, IRCCS — Roma

Идентификаторы

NCT: NCT07724990 · 6991

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗