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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Breast Cancer, Osteoporosis, Osteopenia

Intervention / Treatment
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* Drug: Vivomixx
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Age≥ 35 years Breast cancer stages 1-3 (non metastatic) Under treatment with aromatase inhibitors In menopausal status for ≤10y Estrogen receptor positive tumor CTX ≥300 pg/ml Exclusion criteria Distant metastases Additional active primary malignancy Metabolic bone disease (primary hyperparathyroidism, hyperthyroidism, paget, osteomalacia etc) Glucocorticoid treatment (chronic or high dose >7.5 mg in the last three months) Bisphosphonate treatment for more than 3 months in the last 2 years Bone densitometry (DXA) T-Score <-2 unless not a candidate for antiresorptive therapy (unwilling/unable to take treatment) Lactose intolerant subjects

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dietary supplement Vivomixx<br>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<br>* The intervention consists of 2 sachets a day containing the probiotic Vivomixx, for 6 months<br>|
| Placebo Comparator: Placebo<br>The placebo sachets contain the inactive ingredients maltose and silicon dioxides | Drug: Placebo<br>* The intervention consists of 2 sachets a day of placebo, for 6 months<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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probiotics, aromatase inhibitors, bone mass, postmenopausal