Using a mixed probiotic/prebiotic supplement (MBR-01) to help prevent diarrhea in patients taking abemaciclib for early breast cancer

ISRCTN	ISRCTN11948182
DOI	https://doi.org/10.1186/ISRCTN11948182
Sponsor	Azienda Socio Sanitaria Territoriale di Cremona
Funders	Mednote S.r.l., Copan Italia S.p.a.

Submission date: 10/12/2025
Registration date: 11/12/2025
Last edited: 11/12/2025

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Daniele Generali
Principal investigator, Scientific

Viale Concordia 1
Cremona
26100
Italy

ORCID ID	0000-0001-6002-1530
Phone	+39 (0)372408041
Email	dgenerali@asst-cremona.it

Dr Martina Dester
Public

Viale Concordia 1
Cremona
26100
Italy

Phone	+39 (0)372408041
Email	martina.dester@asst-cremona.it

Study information

Primary study design	Interventional
Allocation	Non-randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Patients were assigned to the control or intervention group based on their willingness to receive prophylactic MBR-01, a standardized probiotic and prebiotic protocol
Purpose	Supportive care
Scientific title	A mixed probiotic/prebiotic intervention (MBR-01) for the management of diarrhea during abemaciclib treatment of early breast cancer: a single-center prospective case–control pilot study
Study objectives	Primary objective: To preliminarily assess whether MBR-01 reduces the incidence and severity of abemaciclib-induced diarrhea. Secondary objectives: 1. To evaluate whether the intervention reduces the need for dose reductions, treatment interruptions, or discontinuations caused by gastrointestinal toxicity. 2. To assess changes in patient-reported stool frequency and consistency collected through daily electronic diaries. 3. To determine the impact of the intervention on health-related quality of life (HRQoL), using the EORTC QLQ-C30 and QLQ-BR23 questionnaires, with a specific focus on emotional, role, and physical functioning (QLQ-C30) as well as body image and sexual functioning (QLQ-BR23). 4. To explore the effects of the intervention on patient-reported outcomes through a custom QoL interference score and diary-based stool frequency measures. 5. To explore changes in gut microbiota composition and diversity from baseline to week 12, and to investigate their potential association with the occurrence and severity of diarrhea.
Ethics approval(s)	Approved 18/10/2019, Comitato Etico ATS Val Padana (Viale Concordia 1, Cremona, 26100, Italy; +39 (0)372408430; comitato.etico@asst-cremona.it), ref: 34236 - 19
Health condition(s) or problem(s) studied	Prevention or symptomatic reduction of abemaciclib-induced diarrhea in patients with early stage hormone receptor positive (HR+)/HER2-negative breast cancer candidate to receive abemaciclib in clinical practice
Intervention	Patients are assigned to the control or intervention group based on their willingness to receive prophylactic MBR-01, a standardized probiotic and prebiotic protocol. Patients in the experimental arm receive the MBR-01 prebiotic/probiotic protocol 4 cp/8 h + abemaciclib 150 mg 1 cp/12 h + letrozole 2.5 mg 1 cp/24 h for 12 weeks. Patients in the control group receive abemaciclib 150 mg 1 cp/12 h + letrozole 2.5 mg 1 cp/24 h for 12 weeks.
Intervention type	Supplement
Primary outcome measure(s)	Incidence and severity of abemaciclib-induced diarrhea measured using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 grading (clinical assessment) at baseline and week 12
Key secondary outcome measure(s)	Need for dose reductions, treatment interruptions, or discontinuations due to diarrhea measured using medical record review and clinician-reported treatment modifications at continuously assessed throughout the 12-week treatment period Patient-reported outcomes (PROMs): stool frequency measured using electronic diary counts (ePRO) at continuously assessed throughout the 12-week treatment period Health-related quality of life (HRQoL): predefined functional domains measured using EORTC QLQ-C30: emotional, role, physical functioning; EORTC QLQ-BR23: body image, sexual functioning; analysis: non-parametric comparative tests (Mann–Whitney U, Wilcoxon signed rank) at baseline and week 12 Patient-reported outcomes (PROMs): exploratory quality of life interference measured using custom composite score derived from electronic diaries at baseline and week 12 Gut microbiota composition and diversity measured using alpha diversity: Shannon, Simpson, Chao1 indices compared via appropriate non-parametric tests; beta diversity: Bray–Curtis, weighted UniFrac, analyzed with PERMANOVA at baseline and week 12 Correlation between microbiota features and diarrhea outcomes measured using Spearman correlation using taxa with significant overall shifts at baseline and week 12 Predictors of grade ≥2 diarrhea measured using multivariable logistic regression including clinical and microbial baseline features at baseline
Completion date	30/09/2025

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	18 Years
Upper age limit	85 Years
Sex	All
Target sample size at registration	20
Total final enrolment	20
Key inclusion criteria	1. Women aged ≥18 years 2. Histologically confirmed HR+/HER2– early breast cancer at high-risk of recurrence (≥4 positive axillary lymph nodes, or 1–3 positive nodes with additional features such as tumor size ≥5 cm, histologic grade 3, or Ki-67 ≥20%), candidate to receive abemaciclib 3. Patients were deemed unsuitable for adjuvant chemotherapy due to comorbidities frailty, or patient preference 4. Eastern Cooperative Oncology Group (ECOG) performance status 0–2 5. Adequate hematologic and organ function 6. Ability to provide fecal samples 7. Ability to provide informed consent
Key exclusion criteria	1. Prior exposure to CDK4/6i 2. Chronic diarrheal disorders 3. Inflammatory bowel disease 4. Intestinal resection affecting absorption 5. Systemic antibiotic, proton pump inhibitors or probiotic use within 4 weeks prior to enrollment 6. Immunosuppressive treatment 7. Concurrent participation in another interventional study
Date of first enrolment	02/01/2023
Date of final enrolment	30/04/2025

Locations

Countries of recruitment

Italy

Study participating centre

ASST of Cremona

Viale Concordia 1
Cremona
26100
Italy

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

Editorial Notes

11/12/2025: Study's existence confirmed by the Azienda Socio Sanitaria Territoriale di Cremona.