Probiotic and Ginger Supplement for Symptoms and Quality of Life in Functional Dyspepsia (SUBTILE)

Official title

Effect of a Combination of Spore-forming Probiotics (Bacillus Coagulans MY01 and Bacillus Subtilis MY02) and Ginger Extract on Symptoms and Quality of Life in Patients With Functional Dyspepsia

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.

Detailed description

Functional dyspepsia (FD) is one of the most common disorders of gut-brain interaction (DGBI), with an estimated prevalence of 7-8% in the general population. It is defined by Rome IV criteria as bothersome postprandial fullness, early satiety, epigastric pain, or burning, persisting for at least 3 months with onset at least 6 months before diagnosis, and without evidence of structural disease. FD is associated with impaired quality of life, psychological distress, and significant health care utilization. Current treatment options, including proton pump inhibitors and prokinetics, have limited efficacy and potential adverse effects when used long term.

Emerging evidence suggests a role of the gastrointestinal microbiota in FD pathophysiology. Alterations in duodenal microbiota, as well as small intestinal bacterial overgrowth (SIBO) promoted by chronic PPI use, have been reported. Probiotics may reduce dyspeptic symptoms, improve gut barrier function, modulate gastric motility, and exert anti-inflammatory effects.

A randomized controlled trial showed that Bacillus coagulans MY01 and Bacillus subtilis MY02 improved FD symptoms compared to placebo, with good safety and tolerability. In parallel, ginger (Zingiber officinale) has a well-documented gastroprotective effect, supported by both preclinical and clinical data, and has been shown to enhance gastric emptying and reduce upper gastrointestinal discomfort.

The present study (SUBTILE, STO-253) is a prospective, multicenter, interventional trial conducted in France, categorized as RIPH2 (research involving human participants at minimal risks and constraints) under French regulations. The study will evaluate the effect of a dietary supplement combining Bacillus coagulans MY01, Bacillus subtilis MY02, and ginger extract (50 mg, 20% gingerols), marketed in France since January 2025 as Symbiosys® Stomalex.

A total of 198 adult patients with FD (Rome IV criteria, normal endoscopy) will be recruited in primary care and gastroenterology practices. After providing informed consent, eligible participants will receive one capsule per day for 8 weeks. The study involves two in-person visits (baseline and Week 8) and one telephone follow-up at Day 28.

The primary endpoint is the change in total PAGI-SYM score from baseline to Week 8.

Secondary endpoints include changes in PAGI-QoL scores, treatment adherence, use of concomitant therapies, evolution of lower gastrointestinal symptoms, global impressions of change from both patients (PGI-C) and physicians (CGI-I), and satisfaction ratings. An exploratory endpoint evaluates psychological impact using the Hospital Anxiety and Depression Scale (HADS). Safety endpoints include frequency and severity of adverse events.

This study will provide additional clinical evidence on the potential role of spore-forming probiotics combined with ginger extract as a complementary non-pharmacological approach to improve digestive symptoms and quality of life in patients with functional dyspepsia.

Interventions

• Dietary supplement Symbiosys® Stomalex (commercial name)
  One oral capsule per day for 8 weeks. Each capsule contains Bacillus coagulans MY01, Bacillus subtilis MY02, and ginger root extract (50 mg, titrated to 20% gingerols).

Primary outcome measures

• Change in PAGI-SYM total score from baseline to Week 8 [Time frame: Baseline (Day 0) and Week 8 (Day 56 ± 3 days)]

Secondary outcome measures (12)

• Change in Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) Scores During Follow-up [Time frame: Baseline, Weeks 2, 4, 6, and 8]
• Change in Patient Assessment of Upper Gastrointestinal Quality of Life (PAGI-QoL) Total Score [Time frame: Baseline, Week 4, and Week 8]
• Patient adherence to study product assessed by patient diary [Time frame: Week 4, and Week 8]
• Use of concomitant medications for dyspeptic symptoms [Time frame: 2 months prior to inclusion and during study period (8 weeks)]
• Evolution of lower gastrointestinal symptoms [Time frame: Baseline and Week 8]
• Patient's Global Impression of Change (PGI-C) [Time frame: Week 8]
• Clinical Global Impression of Improvement (CGI-I) [Time frame: Week 8]
• Patient satisfaction with study product [Time frame: Week 8]
• Physician satisfaction with study product [Time frame: Week 8]
• Exploratory: Change in Hospital Anxiety and Depression Scale (HADS) score [Time frame: Baseline and Week 8]
• Safety and tolerability (Adverse Events) [Time frame: From consent signature to Week 8 (end of study)]
• Patient adherence to study product assessed by capsule count [Time frame: Week 4 and Week 8]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Gerard DASSA — Istres

Identifiers

NCT: NCT07212907 · SUBTILE - STO 253 · 2025-A01409-40

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗