The Effects of a Novel Probiotic Supplement on Menopausal Symptoms and Bone Health (MPS)

The Effects of a Novel Probiotic Supplement on Menopausal Symptoms and Bone Health: A Randomized, Double-blind, Parallel, Placebo-Controlled, Multi-Centre Study

This Phase II study is designed to evaluate the potential effects of a novel probiotic supplement on the severity of global menopause symptoms (e.g., psychological, somatic, urogenital symptoms) and on bone health in postmenopausal women.

Study Overview

• Status: Completed
• Conditions: Menopause
• Intervention / Treatment: Dietary supplement: Probiotic; Other: Placebo

Detailed Description

Menopause is a natural phase in which a woman's menstrual cycle permanently cease. During this time, women undergo many biological changes, including a decline of estrogen level or alterations in the vaginal microflora. This can result in the onset of various physiological and psychological menopause-related symptoms which may continue into postmenopausal years.

The present study aims to evaluate the potential effects of a probiotic supplement on global menopause symptoms including psychological, somatic and urogenital symptoms. It is hypothesized that this probiotic, consumed over a 12-week period, will help reduce the symptoms of menopause by modulating the mucosal microflora of the vaginal linings. Additionally, it is hypothesized that the continued consumption of this probiotic combination over a total of 48 weeks will aid in the overall maintenance of bone health and may ameliorate bone density loss.

144 healthy postmenopausal women (≥ 40 to < 60 years old) in the U.S. who are experiencing menopause-related symptoms will be randomized to the study (12-week period), and a subset (72 postmenopausal women) will continue the study for an additional 36 weeks (Bone Health Study).

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Lake Worth, Florida, United States, 33461
      • Altus Research
    • Port Saint Lucie, Florida, United States, 34952
      • Health Awareness Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research Inc.
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Viable Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 years to 57 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Healthy post-menopausal woman
• Last menstrual period has occurred at least 12 months prior to screening
• ≥40 to <60 years old
• Vaginal pH ≥ 5
• MRS score ≥ 20
• Willing and able to give written informed consent
• Willing to consume IP or placebo, complete questionnaires, records, and daily diaries associated with the study and to complete all clinical study visits
• Willingness to discontinue consumption of probiotic supplements and food containing added probiotics and/or prebiotics (e.g. yogurts with live, active cultures or supplements) o Note: Screened participants will be eligible to participate after completing a 4-week wash-out period.

Exclusion Criteria:

• Milk or soy allergy
• Women with induced menopause through full or partial hysterectomy, chemotherapy or radiation
• Consumption of natural health products used to treat menopausal symptoms such as phytoestrogens, Black Cohosh, dehydroepiandrosterone (DHEA), Dong Quai, vitamin E (>250 IU/day), high consumption of soy food products, unless a 1-month wash-out period has been completed prior to study commencement
• Currently undergoing or have previously undergone HT for treatment of menopausal symptoms, unless a three-month washout has been completed prior to study commencement

• Active vaginal infections/abnormalities (e.g. active urinary tract infection (UTI), genital hemorrhage of unknown origin)

  o Note: Screened participants with infections would be eligible to participate 4 weeks after completing their course of treatment (wash-out period).

• Use of any vaginal medication, vaginal rinses and/or moisturizers, gels containing xylocaine or other analgesic products to decrease pain during intercourse, 1 week before and during study

• Use of any antibiotic drug within 1 month of screening

  o Note: Screened participants could be eligible to participate after a 2-week wash-out period.

• Participants previously diagnosed with hyperparathyroidism and/or hyperthyroidism
• Participation in other clinical studies in the past 6 months
• History of alcohol or drug abuse in the 12 months prior to screening
• History of cancer (except localized skin cancer without metastases) within five (5) years prior to screening
• History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influences the results or the potential subject's ability to participate in the study
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs (i.e. Crohn's disease, short bowel, acute or chronic pancreatitis or pancreatic insufficiency)
• History of a surgical procedure for the treatment of obesity (e.g., gastric bypass, gastric banding)
• Currently consuming more than 2 standard alcoholic beverages a day. A standard alcoholic beverage is defined as 12 ounces of beer, five (5) ounces of wine, or 1.5 ounces of liquor
• Difficulty swallowing large pills or large quantities of pills
• Any condition or abnormality that, in the opinion of the investigator, would compromise the safety of the subject or the quality of the study data

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; Probiotics in a capsule.	Dietary supplement: Probiotic; Dosing regimen of one capsule daily for a maximum of 48 weeks.
Placebo Comparator: Placebo; Non active ingredients in a capsule.	Other: Placebo; Dosing regimen of one capsule daily for a maximum of 48 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the global Menopause Rating Scale (MRS) score	Assessed using Menopause Rating Scale (MRS) rating scale. 11 questions on a scale from no complaints (0) to very severe symptoms (4). Subscores are added to create a composite or total score. A higher score indicates a greater severity of menopausal symptoms.	Measured on weeks -2 (screening visit), 0, 4, 8, 12, and 48.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in individual components of the Menopause Rating Scale (MRS) (psychological, somatic and urogenital symptoms)	Assessed using Menopause Rating Scale (MRS) rating scale. 11 questions on a scale from no complaints (0) to very severe symptoms (4). Subscores are added to create the 3 dimensions scores. A higher score indiactes a greater severity of perceived menopausal symptoms.	Measured on weeks -2 (screening visit), 0, 4, 8, 12, and 48.
Change from baseline in vaginal pH	Vaginal swabs will be collected for pH testing, using pH strips for screening and to measure evolution of pH throughout first part of the study.	Measured on weeks -2 (screening visit), 0, and 12.
Change from baseline in vaginal microbiota	Effects of the probiotic intervention on overall microbiota composition will be assessed with a vaginal swab. In addition, recovery of the probiotic strains in the vaginal samples will be assessed.	Measured on weeks 0 and 12.
Change from baseline in the Patient Health Questionnaire (PHQ-9) total score	Depression measured with the Patient Health Questionnaire (PHQ-9). 10 questions. The first 9 questions are on a scale from not at all bothered by symptoms (0) to bothered by symptoms nearly everyday (3). To arrive at the total score, the individual question scores are added. A score of 5-9 indicates minimal symptoms, a score of 10-14 indicates minor depression, dysthymia, or mild Major Depression, a score of 15-19 indicates moderately sever Major Depression and a score of greater than 20 indicates severe Major Depression.	Measured on weeks 0, 4, 8, 12, and 48.
Change from baseline in the Pittsburgh Sleep Quality Index (PSQI) global score	Sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). 9 questions. It consists of seven components including: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medications, and daytime dysfunction. Each component score ranges from 0 to 3, whereby 3 reflects the negative extreme, for a global score range of 0 to 21. A score of 5 or greater indicates the reporter has poor sleep quality.	Measured on weeks 0, 4, 8, 12, and 48.
Change from baseline in the Vulvovaginal Symptoms Questionnaire (VSQ) total score.	Vulvar and vaginal atrophy measured with the Vulvovaginal Symptoms Questionnaire (VSQ). 21 yes (1) or no (0) questions in 4 scales: Symptoms, Emotions, Life-impact, Sexual impact. Total score will be the sum of the first 17 questions if non-sexually active or of the 21 questions if sexually active. A higher score indicates a greater severity of vulvar and vaginal atrophy.	Measured on weeks 0, 4, 8, 12, and 48.
Change in baseline in the Michigan Incontinence Symptom Index (M-ISI) mean score	Urinary incontinence measured with the Michigan Incontinence Symptom Index (M-ISI). 10 questions with different scales all numbered 0-4. The total score is derived from taking the mean of the 10 reported scores. A higher score indicates a higher severity of incontinence.	Measured on weeks 0, 4, 8, 12, and 48.
Change from baseline in the Generalized Anxiety Disorder-7 (GAD-7) total score	Anxiety measured with the Generalized Anxiety Disorder-7 (GAD-7). 7 questions scaled from not at all sure (0) to nearly every day (3). Total score is derived from the addition of answer to each question. A higher score indicates a higher level of detected anxiety.	Measured on weeks 0, 4, 8, 12, and 48.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in levels of Metabolic Syndrome biomarkers (serum cholesterol [total, LDL, HDL], serum Triglycerides)	To evaluate any beneficial changes in Metabolic Syndrome that may result from probiotic supplementation.	Measured on weeks 0, 12, 24, and 48.
Change in baseline of levels of pro-inflammatory cytokines Interleukin-17 (IL-17), RANKL and Tumor Necrosis Factor (TNF)	Serum levels may uncover possible anti-inflammatory effects of probiotics	Measured on weeks 0, 12, 24, and 48.
Change from baseline in gut microflora	Fecal samples will be evaluated for the persistence of the supplemented probiotics in the gut, and their effect on the microbial gut population.	Measured on weeks 0, 12, 24, and 48.
Change from baseline in dual-energy X-ray Absorptiometry (DXA) scans	To assess bone health by measuring BMD.	Measured on weeks 0 and 48.
Change from baseline in the Fracture Risk Assessment Tool (FRAX)	To estimate an individual's fracture risk.	Measured on weeks 0 and 48.
Change from baseline in levels of bone resorption and bone formation markers (serum C-terminal telopeptide [CTx], serum procollagen type I N propeptide [PINP], osteocalcin, and bone-specific alkaline phosphatase [BAP]).	To assess bone health using blood samples.	Measured on weeks 0, 12, 24, and 48.

Collaborators and Investigators

• Sponsor: Lallemand Health Solutions
• Collaborators: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2019
• Primary Completion (Actual): November 18, 2020
• Study Completion (Actual): April 23, 2021

Study Registration Dates

• First Submitted: June 25, 2019
• First Submitted That Met QC Criteria: June 26, 2019
• First Posted (Actual): June 27, 2019

Study Record Updates

• Last Update Posted (Actual): July 28, 2022
• Last Update Submitted That Met QC Criteria: July 27, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Depression; Anxiety; Urinary incontinence; Probiotics; Sleep quality; Menopausal symptoms; Bone health; Vulvar and vaginal atrophy; Vaginal microflora; Metabolic syndrome biomarkers; Gut microflora; Bone resorption markers; Bone formation markers; Bone Mineral Density (BMD); Fracture risk assessment
• Other Study ID Numbers: MPS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No