- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03290651
Probiotics and Breast Health
Re-setting the Breast Microbiome to Lower Inflammation and Risk of Cancer.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Certain bacteria, particularly Gram negatives, are major causes of inflammation. In fact, the lipopolysaccharides from these bacteria are used in vast numbers of studies to induce inflammation and study disease. Many cancers are the result of inflammatory processes. Breast cancer is a major cause of illness and death in women and inflammatory processes are one of the foci of investigation; however, not yet from the stand point that bacteria in the breast may be the instigators of cancer development. The investigators were the first in the world to describe the breast microbiota and show that the bacterial profiles are more pathogenic in women with cancer than in tissues of healthy controls. This work has been validated by others. Although this does not prove a cause-and-effect link with breast cancer, such linkages have been shown in stomach and colon cancers. If researchers assume there is a link, then how can the inflammatory microbiota be re-set to one that is somehow beneficial and able to reduce inflammation and potential cancer induction?
The concept of probiotics emerged from the quest to reset the disrupted microbiota of the gut and upper respiratory tract. This investigational group has led the world in doing the same in the urogenital tract of women.
The researchers would like to test their theory that taking probiotic lactobacilli by mouth can lead to these organisms reaching the breast tissue and helping displace the harmful bacteria and reducing inflammation. A study in Spain has shown that oral intake of probiotic lactobacilli can not only cure mastitis, but lead to the lactobacilli reaching the milk glands. Women who breast feed for more than six months (and thereby pass along lactic acid bacteria to the infant from the breast milk) have a reduced risk of breast cancer.
The investigators hypothesize that the breast microbiome of women at risk of cancer has the same profile as women with cancer and that oral administration of probiotic lactobacilli can reset this to one found in healthy women. They also hypothesize the breast tissue of these at-risk patients is contaminated by environmental toxins.
The project plan is to test the concept of re-setting the breast tissue microbiota in women at risk of cancer, to one more aligned with health.
Samples will be tested for relative bacterial abundance to determine any shift in bacterial breast tissue composition by next-generation sequencing and bioinformatics. Samples will also be tested for inflammatory markers using Luminex technology, and for mercury, arsenic and pesticides using LC-MS as described in previous studies.
Twenty women at high-risk for breast cancer (See Inclusion Criteria) will be randomized (10 each) to receive either probiotic or placebo, once a day for 90 days. This capsule is approved in Canada and widely available and contains 2.5 billion CFU viable bacterial cells of each of the following strains: Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14. Both active capsules and placebo will be provided by the manufacturer Chr Hansen (Denmark). Samples will be collected at t=0 (enrollment), t=1 (end of 90 days) and t=2(30 days post-treatment).
Twenty women will act as healthy controls (See Inclusion Criteria) and will be randomized (10 each) as described above for the high-risk group.
At each time point, samples collected will include:
- Breast skin swab - a cotton tipped swab with be moistened with sterile water and the passed over the skin on the breast 10 times.
- Needle aspirate - a 22-gauge needle into the breast tissue with repeated passage under suction until aspirate material is identified in the needle hub. This material would then be placed in normal saline.
- Nipple aspirate - the participant will be asked to massage their breast from chest wall to nipple for several minutes as needed. Using a hand-held modified breast pump placed over the nipple, nipple aspirate fluid will be drawn out and into a capillary tube.
- Blood draw - one 6mL EDTA plasma tube using standard phlebotomy procedures. Samples will be analyzed for relative bacterial abundance (next-generation sequencing), inflammatory markers (Luminex technology).
- Urine - 100mL sample that will be tested for heavy metals and pesticides using LC-MS.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Ontario
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London, Ontario, Canada, N6A 4V2
- St. Joseph's Health Care
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Women at high risk of developing breast cancer who have never had breast cancer (≥ 25% lifetime risk and/or BRCA1 or BRCA2 positive) will be included in the high risk group, while female family members of cancer patients or friends of patients, as well as patients to the breast clinic who are seen for other reasons not related to cancer will be offered participation in the control group.
Exclusion Criteria:
- Exclusion criteria include: immunosuppression (ongoing high dose steroids, immunosuppressive condition such as HIV), personal history of breast cancer, patients declining needle aspiration biopsy or probiotic/placebo treatment, ongoing daily oral probiotic treatment at time of diagnosis. Patients on chronic or recent (within 2 weeks) antibiotic therapy will also be excluded.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Probiotic Natural Health Product - RepHresh Pro-B
One capsule contains 2.5 billion CFU of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14.
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Participants will take the probiotic or placebo daily for 90 days.
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Placebo Comparator: Placebo
Placebo.
It is the same composition as the active capsule, without the bacteria.
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Participants will take the probiotic or placebo daily for 90 days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in breast microbiota
Time Frame: 90 days post collection period
|
The diversity of the breast microbiota analysed using next-generation sequencing.
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90 days post collection period
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Testing of inflammatory markers and pollutants
Time Frame: 90 days post collection period
|
Blood samples will be testing by luminex for inflammatory cytokine/chemokine markers.
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90 days post collection period
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Testing for environmental pollutants - heavy metals.
Time Frame: 90 days post collection period
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Urine and blood will be tested for heavy metals using LC-MS.
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90 days post collection period
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Testing for environmental pollutants - pesticides.
Time Frame: 90 days post collection period
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Urine and blood will be tested for pesticides using LC-MS.
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90 days post collection period
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Gregor Reid, Ph.D., Lawson Health Research Institute
- Principal Investigator: Muriel Brackstone, M.D., St. Joseph's Health Care London
Publications and helpful links
General Publications
- Arroyo R, Martin V, Maldonado A, Jimenez E, Fernandez L, Rodriguez JM. Treatment of infectious mastitis during lactation: antibiotics versus oral administration of Lactobacilli isolated from breast milk. Clin Infect Dis. 2010 Jun 15;50(12):1551-8. doi: 10.1086/652763.
- Urbaniak C, Cummins J, Brackstone M, Macklaim JM, Gloor GB, Baban CK, Scott L, O'Hanlon DM, Burton JP, Francis KP, Tangney M, Reid G. Microbiota of human breast tissue. Appl Environ Microbiol. 2014 May;80(10):3007-14. doi: 10.1128/AEM.00242-14. Epub 2014 Mar 7.
- Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, Reid G. The Microbiota of Breast Tissue and Its Association with Breast Cancer. Appl Environ Microbiol. 2016 Jul 29;82(16):5039-48. doi: 10.1128/AEM.01235-16. Print 2016 Aug 15.
- Hieken TJ, Chen J, Hoskin TL, Walther-Antonio M, Johnson S, Ramaker S, Xiao J, Radisky DC, Knutson KL, Kalari KR, Yao JZ, Baddour LM, Chia N, Degnim AC. The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease. Sci Rep. 2016 Aug 3;6:30751. doi: 10.1038/srep30751.
- Chan AA, Bashir M, Rivas MN, Duvall K, Sieling PA, Pieber TR, Vaishampayan PA, Love SM, Lee DJ. Characterization of the microbiome of nipple aspirate fluid of breast cancer survivors. Sci Rep. 2016 Jun 21;6:28061. doi: 10.1038/srep28061.
- Zackular JP, Baxter NT, Iverson KD, Sadler WD, Petrosino JF, Chen GY, Schloss PD. The gut microbiome modulates colon tumorigenesis. mBio. 2013 Nov 5;4(6):e00692-13. doi: 10.1128/mBio.00692-13.
- Mira-Pascual L, Cabrera-Rubio R, Ocon S, Costales P, Parra A, Suarez A, Moris F, Rodrigo L, Mira A, Collado MC. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol. 2015 Feb;50(2):167-79. doi: 10.1007/s00535-014-0963-x. Epub 2014 May 9.
- Sitas F. Twenty five years since the first prospective study by Forman et al. (1991) on Helicobacter pylori and stomach cancer risk. Cancer Epidemiol. 2016 Apr;41:159-64. doi: 10.1016/j.canep.2016.02.002. Epub 2016 Feb 26.
- Macklaim JM, Clemente JC, Knight R, Gloor GB, Reid G. Changes in vaginal microbiota following antimicrobial and probiotic therapy. Microb Ecol Health Dis. 2015 Aug 14;26:27799. doi: 10.3402/mehd.v26.27799. eCollection 2015.
- Bisanz JE, Enos MK, Mwanga JR, Changalucha J, Burton JP, Gloor GB, Reid G. Randomized open-label pilot study of the influence of probiotics and the gut microbiome on toxic metal levels in Tanzanian pregnant women and school children. mBio. 2014 Oct 7;5(5):e01580-14. doi: 10.1128/mBio.01580-14.
- Bisanz JE, Seney S, McMillan A, Vongsa R, Koenig D, Wong L, Dvoracek B, Gloor GB, Sumarah M, Ford B, Herman D, Burton JP, Reid G. A systems biology approach investigating the effect of probiotics on the vaginal microbiome and host responses in a double blind, placebo-controlled clinical trial of post-menopausal women. PLoS One. 2014 Aug 15;9(8):e104511. doi: 10.1371/journal.pone.0104511. eCollection 2014.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 110181
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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