Overview

Functional dyspepsia (FD) is a frequent functional gastrointestinal disorder characterized by bothersome postprandial fullness, early satiety, epigastric pain, or burning, in the absence of any structural or metabolic cause. It significantly impairs quality of life and has limited therapeutic options, as conventional treatments such as proton pump inhibitors often show modest efficacy and may cause side effects with long-term use.

The gut and duodenal microbiota may play a role in FD. Spore-forming probiotics such as Bacillus coagulans MY01 and Bacillus subtilis MY02 have shown beneficial effects on FD symptoms in a randomized controlled trial. Ginger (Zingiber officinale) has a long history of traditional use as a gastroprotective agent and is supported by clinical and non-clinical data for improving gastric motility and related symptoms.

This study (SUBTILE, STO-253) is a prospective, interventional, multicenter trial conducted in France. It will evaluate the effect of a dietary supplement containing Bacillus coagulans MY01, Bacillus subtilis MY02, and ginger extract (50 mg, 20% gingerols) on FD symptoms and quality of life.

A total of 198 adult patients diagnosed with FD according to Rome IV criteria and with a normal upper endoscopy will be recruited in primary care and gastroenterology practices. Participants will take one capsule of the study product daily for 8 weeks.

The primary outcome is the change in the Patient Assessment of Gastrointestinal Symptom Severity (PAGI-SYM) total score between baseline and Week 8.

Secondary outcomes include changes in quality of life (PAGI-QoL), treatment adherence, use of concomitant medications, evolution of lower gastrointestinal symptoms, patient and physician global impressions of change (PGI-C, CGI-I), and satisfaction (Likert scales). An exploratory objective will assess psychological impact using the Hospital Anxiety and Depression Scale (HADS).

The study includes two site visits (baseline and end of study) and one telephone follow-up at Day 28. Safety and tolerability will be monitored through active reporting of adverse events.

The trial aims to provide new evidence on the role of probiotics combined with ginger extract as a non-pharmacological strategy to improve digestive comfort and quality of life in patients with functional dyspepsia.

Eligibility

Inclusion Criteria:

• Adults (male or female) aged ≥18 years.
• Diagnosis of functional dyspepsia (FD) according to Rome IV criteria, with normal upper endoscopy including negative Helicobacter pylori test. Rome IV criteria define FD as the presence of one or more of the following symptoms: bothersome postprandial fullness, early satiety, epigastric pain, or epigastric burning, occurring at least 3 days per week during the last 3 months, with symptom onset at least 6 months prior to diagnosis.
• PAGI-SYM total score \>1 at baseline.
• Ability to comply with study requirements and provide signed written informed consent before any study-related procedures.
• Ability to complete the patient diary and questionnaires, in the investigator's opinion (sufficient reading and language comprehension).
• For women of childbearing potential : Negative urine pregnancy test immediately before starting study product ; Agreement to use an approved method of contraception for the duration of the study, unless meeting criteria for menopause (≥12 months of spontaneous amenorrhea). Women of childbearing potential are defined as all women physiologically capable of becoming pregnant, including those whose career, lifestyle, or sexual orientation normally precludes heterosexual intercourse.
• Affiliation with a national health insurance or social security system.

Exclusion Criteria:

• Use within 2 weeks prior to baseline of treatments that could interfere with study evaluation, including Bacillus coagulans MY01, Bacillus subtilis MY02, ginger, peppermint, or antibiotics.
• Known allergy or hypersensitivity to any component of the investigational product.
• Contraindication or specific warning related to the investigational product, including use of anticoagulants.
• Use of immunosuppressive therapy within the last 3 months.
• Use of medications affecting gastrointestinal motility or sensitivity, including opioids, GLP-1 analogs, neuroleptics, antiemetics, or anticholinergics. (Stable antidepressant therapy allowed.)
• Significant changes in diet or physical activity within 2 weeks prior to baseline or anticipated during the study period.
• Active somatic or psychiatric disorder that could explain dyspeptic symptoms (e.g., active cancer, inflammatory disease). Stable use of one antidepressant is allowed for psychiatric indication.
• Active Helicobacter pylori infection.
• Predominant symptoms of gastroesophageal reflux disease (GERD) or irritable bowel syndrome (IBS).
• Functional diarrhea or functional constipation as defined by Rome IV criteria.
• History of abdominal surgery within the past year, except appendectomy, cholecystectomy, inguinal hernia repair, or splenectomy.
• Pregnant or breastfeeding women.
• Individuals under legal guardianship or curatorship.
• Participation in another interventional clinical trial and receipt of an investigational product within 30 days prior to baseline.
• Any acute or chronic medical or psychiatric condition that, in the investigator's judgment, could interfere with study assessments, including but not limited to severe hepatic or renal insufficiency, immunodeficiency, or substance abuse (alcohol or drugs).
• Any personal condition or circumstance that, in the investigator's judgment, would make full participation in the study unlikely or impossible.