CBM588, Clostridium Butyricum Miyairi, Gastrointestinal Symptoms, Pancreatic Cancer, Pancreatic Diseases, Pancreatoduodenectomy
Conditions
Keywords
Pancreatic Cancer, Pancreatic Diseases, Gastrointestinal Symptoms, Clostridium Butyricum Miyairi
Brief summary
This is a prospective, randomized, double-blind, single-center clinical trial designed to evaluate the effects of Clostridium butyricum CBM588 supplementation on postoperative diarrhea, gastrointestinal symptoms, and quality of life in patients undergoing pancreaticoduodenectomy for periampullary neoplasms. Oncological outcomes, including disease-free survival and overall survival, will be monitored as secondary endpoints during follow-up.
Detailed description
Pancreaticoduodenectomy is associated with significant postoperative gastrointestinal complications, particularly chronic diarrhea, which negatively impacts nutritional status, quality of life, and the ability to complete adjuvant oncologic treatments. Increasing evidence suggests that alterations in the gut microbiota and reduced production of short-chain fatty acids, especially butyrate, play a key role in postoperative gastrointestinal dysfunction. Clostridium butyricum CBM588 is a butyrate-producing probiotic with a well-established safety profile and demonstrated efficacy in the management of gastrointestinal disorders. This study aims to assess whether supplementation with Clostridium butyricum CBM588 can reduce postoperative diarrhea-hypothesized as a 40-60% relative reduction compared with placebo-and improve gastrointestinal symptoms and quality of life in patients undergoing pancreaticoduodenectomy. In addition to gastrointestinal and quality-of-life outcomes, patients will be followed longitudinally for oncological outcomes, including disease-free survival and overall survival, in order to explore potential associations between postoperative gastrointestinal recovery, nutritional status, and long-term clinical outcomes. A total of 158 patients will be randomized in a 1:1 ratio to receive either Clostridium butyricum CBM588 or placebo for 3 months following hospital discharge. All participants in both study arms will receive standard postoperative care, including individualized nutritional counseling based on a comprehensive assessment of nutritional status and body composition (including bioimpedance analysis) according to a standardized nutritional scheme, as well as pancreatic enzyme replacement therapy prescribed as pancrelipase 50,000 IU with each main meal and 25,000 IU with each snack, in addition to other medical or pharmacological treatments as clinically indicated. Patients will be followed for gastrointestinal outcomes and quality of life during the intervention period and for disease-free survival and overall survival during long-term follow-up. All participants will be provided with a patient diary to record date and time of study product administration, number of tablets taken, daily bowel movements, and stool consistency according to the Bristol Stool Form Scale. The enrollment period is expected to last approximately 30 months. The intervention will be administered for 3 months following hospital discharge. The primary endpoint will be assessed at the end of the treatment period, while secondary oncological endpoints will be evaluated during an additional 24-month follow-up.
Interventions
Butirrisan® contains ≥4.5 × 10⁵ CFU of Clostridium butyricum CBM588 per tablet. Participants will receive 6 tablets per day (3 tablets in the morning and 3 tablets in the evening) starting at hospital discharge and continuing for 3 months.
OTHERPlacebo
Placebo tablets contain lactose and inert components and will be administered at a dosage of 6 tablets per day (3 tablets in the morning and 3 tablets in the evening) starting at hospital discharge and continuing for 3 months.
Sponsors
Casa di Cura Dott. Pederzoli
PharmExtracta S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Statistical Analysts
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Written informed consent * Patients undergoing pancreaticoduodenectomy * Candidates for upfront surgery without previous neoadjuvant chemotherapy or radiotherapy * Patients with benign or malignant periampullary neoplasms
Exclusion criteria
* Age \< 18 years * Previous or current use of Clostridium butyricum CBM588 * Lactose intolerance * Neoadjuvant chemotherapy or radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative diarrhea - mean daily stool frequency | Baseline (preoperative), 1-month post-discharge, 3 months post-discharge | Mean number of bowel movements per day (Unit of Measure: bowel movements/day \[count\]), recorded using a patient-reported daily stool diary completed after hospital discharge. The primary comparison is between patients receiving Clostridium butyricum CBM588 and placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stool consistency - Bristol Stool Form Scale (BSFS) | Baseline (preoperative), 1-month post-discharge, and 3 months post-discharge | Stool consistency assessed using the Bristol Stool Form Scale, a 7-point ordinal scale ranging from Type 1 to Type 7 (Unit of Measure: score on a scale, 1-7); higher scores indicate looser or watery stools. Data collected through a patient-reported daily stool diary. |
| Health-related quality of life. European Organisation for Research and Treatment of Cancer - Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Baseline (preoperative), 1-month post-discharge, and 3 months post-discharge. | Health-related quality of life measured with the EORTC QLQ-C30 Global Health Status/QoL scale (Unit of Measure: score on a scale, 0-100); higher scores indicate better quality of life. Collected via follow-up questionnaires. |
| Pancreatic cancer-specific quality of life - European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Pancreatic Cancer Module 26 (EORTC QLQ-PAN26) | Baseline (preoperative), 1-month post-discharge, and 3 months post-discharge. | Pancreatic cancer-specific quality of life assessed using the EORTC QLQ-PAN26 questionnaire (Unit of Measure: score on a scale, 0-100); for symptom scales/items, higher scores indicate worse symptoms/problems (per EORTC scoring). Collected via follow-up questionnaires. |
| Disease-free survival (DFS) | 12 months and 24 months post-discharge | Time from surgery to first documented disease recurrence or death from any cause, whichever occurs first (Unit of Measure: months). Assessed during follow-up through clinical records and telephone interviews. |
| Overall survival (OS) | 12 months and 24 months post-discharge | Time from surgery to death from any cause (Unit of Measure: months). Assessed during follow-up through clinical records and telephone interviews. |
Countries
Italy
Contacts
CONTACTErica Pizzocaro, MSC
CONTACTAlice Cattelani, MD
PRINCIPAL_INVESTIGATORGiovanni Butturini, MD, PhD
Ospedale Pederzoli
Outcome results
None listed