Vivomixx for Prevention of Bone Loss in Women With Breast Cancer Treated With an Aromatase Inhibitor

The Efficacy of the Probiotic Supplement Vivomixx on Prevention of Bone Loss in Early Menopausal Women With Breast Cancer Treated With an Aromatase Inhibitor

This study evaluates the efficacy of the probiotic food supplement Vivomixx in the prevention of bone loss occurring in post menopausal women with breast cancer treated with an aromatase inhibitor. Half of the participants will receive Vivomixx while the other half will receive a placebo. The primary endpoint is to assess changes of bone turnover markers during the period of 6 months.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer; Osteoporosis, Osteopenia
• Intervention / Treatment: Drug: Vivomixx; Drug: Placebo

Detailed Description

Aromatase inhibitors function to reduce estrogen levels. They are considered first-line treatment for postmenopausal women with estrogen receptor-positive breast cancer. Estrogen depletion leads to significant loss of bone mineral density and an increased fracture risk. One contributing mechanism to "estrogen deficiency associated bone loss" is the increase in systemic and local gut inflammatory responses upon estrogen deficiency. Probiotics have been shown to decrease inflammatory cytokine formation in both the systemic circulation and gut.

Vivomixx is a high potency probiotic medical food designated for the dietary management of inflammatory gut conditions in adults and children and is currently being studied in clinical trials in a wide variety of inflammatory conditions such as asthma and diabetes. In preclinical studies Vivomixx has been shown to protect from estrogen deficient bone loss.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sigal Shaklai, M.D, Ph.D; Phone Number: +972-3-6973732; Email: Sigal.shaklai@gmail.com
• Study Contact Backup: Name: Vanessa Rouach, M.D; Phone Number: +972-3-6973732; Email: vanessar@tlvmc.gov.il

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria

1. Age≥ 35 years
2. Breast cancer stages 1-3 (non metastatic)
3. Under treatment with aromatase inhibitors
4. In menopausal status for ≤10y
5. Estrogen receptor positive tumor
6. CTX ≥300 pg/ml

Exclusion criteria

1. Distant metastases
2. Additional active primary malignancy
3. Metabolic bone disease (primary hyperparathyroidism, hyperthyroidism, paget, osteomalacia etc)
4. Glucocorticoid treatment (chronic or high dose >7.5 mg in the last three months)
5. Bisphosphonate treatment for more than 3 months in the last 2 years
6. Bone densitometry (DXA) T-Score <-2 unless not a candidate for antiresorptive therapy (unwilling/unable to take treatment)
7. Lactose intolerant subjects

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dietary supplement Vivomixx; Vivomixx sachets contains a mixture of 450 billion viable lyophilized bacteria from 8 strains: Lactobacillus paracasei DSM 24733, Lactobacillus plantarum DSM 24730, Lactobacillus acidophilus DSM 24735, Lactobacillus delbrueckii subspecies bulgaricus DSM 24734, Bifidobacterium longum DSM 3 24736, Bifidobacterium infantis DSM 24737, Bifidobacterium breve DSM 24732, and Streptococcus thermophilus DSM 24731	Drug: Vivomixx; The intervention consists of 2 sachets a day containing the probiotic Vivomixx, for 6 months
Placebo Comparator: Placebo; The placebo sachets contain the inactive ingredients maltose and silicon dioxides	Drug: Placebo; The intervention consists of 2 sachets a day of placebo, for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Collagen type 1 cross-linked C-telopeptide (CTX)	Change in percent in CTX in serum compared to placebo	3-6 months
Serum type 1 procollagen (N-terminal) P1NP	Change in percent in serum in P1NP compared to placebo	3-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alkaline phosphatase/ bone specific alkaline phosphatase	Change in percent in alkaline phosphatase/ bone specific alkaline phosphatase in serum compared to placebo	3-6 months
Osteocalcin	Change in percent in osteocalcin in serum compared to placebo	3-6 months
Sclerostin	Change in percent in sclerostin in serum compared to placebo	3-6 months
Tumor-necrosis factor-alpha	Change in percent in tumor-necrosis factor-alpha in serum compared to placebo	3-6 months
Interleukin-17	Change in percent in interleukin-17 in serum compared to placebo	3-6 months
Receptor activator of nuclear factor kappa B ligand (RANK-ligand)	Change in percent in RANK-ligand in serum compared to placebo	3-6 months

Collaborators and Investigators

• Sponsor: Tel-Aviv Sourasky Medical Center
• Collaborators: Perrigo Company
• Investigators: Study Director: Naftali Stern, M.D, Tel-Aviv Sourasky Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2019
• Primary Completion (Anticipated): April 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: April 25, 2018
• First Submitted That Met QC Criteria: April 25, 2018
• First Posted (Actual): May 8, 2018

Study Record Updates

• Last Update Posted (Actual): January 17, 2019
• Last Update Submitted That Met QC Criteria: January 16, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: aromatase inhibitors; probiotics; postmenopausal; bone mass
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Musculoskeletal Diseases; Bone Diseases; Breast Neoplasms; Osteoporosis; Bone Diseases, Metabolic
• Other Study ID Numbers: 0124-18-TLV

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No