Clinical trial NCT04001088: The Effects of a Novel Probiotic Supplement on Menopausal Symptoms and Bone Health
Official title: The Effects of a Novel Probiotic Supplement on Menopausal Symptoms and Bone Health: A Randomized, Double-blind, Parallel, Placebo-Controlled, Multi-Centre Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Menopause
Keywords: Probiotics
Menopausal symptoms
Bone health
Vulvar and vaginal atrophy
Vaginal microflora
Anxiety
Depression
Urinary incontinence
Metabolic syndrome biomarkers
Sleep quality
Gut microflora
Bone resorption markers
Bone formation markers
Bone Mineral Density (BMD)
Fracture risk assessment
Lead sponsor: Lallemand Health Solutions
Sponsor class: INDUSTRY
Collaborators: name: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
First posted: 2019-06-27
Enrollment: 144
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in the global Menopause Rating Scale (MRS) score
timeFrame: Measured on weeks -2 (screening visit), 0, 4, 8, 12, and 48.
Secondary outcomes:
measure: Change from baseline in individual components of the Menopause Rating Scale (MRS) (psychological, somatic and urogenital symptoms)
timeFrame: Measured on weeks -2 (screening visit), 0, 4, 8, 12, and 48.
measure: Change from baseline in vaginal pH
timeFrame: Measured on weeks -2 (screening visit), 0, and 12.
measure: Change from baseline in vaginal microbiota
timeFrame: Measured on weeks 0 and 12.
measure: Change from baseline in the Patient Health Questionnaire (PHQ-9) total score
timeFrame: Measured on weeks 0, 4, 8, 12, and 48.
measure: Change from baseline in the Pittsburgh Sleep Quality Index (PSQI) global score
timeFrame: Measured on weeks 0, 4, 8, 12, and 48.
measure: Change from baseline in the Vulvovaginal Symptoms Questionnaire (VSQ) total score.
timeFrame: Measured on weeks 0, 4, 8, 12, and 48.
measure: Change in baseline in the Michigan Incontinence Symptom Index (M-ISI) mean score
timeFrame: Measured on weeks 0, 4, 8, 12, and 48.
measure: Change from baseline in the Generalized Anxiety Disorder-7 (GAD-7) total score
timeFrame: Measured on weeks 0, 4, 8, 12, and 48.
Other outcomes:
measure: Change from baseline in levels of Metabolic Syndrome biomarkers (serum cholesterol [total, LDL, HDL], serum Triglycerides)
timeFrame: Measured on weeks 0, 12, 24, and 48.
measure: Change in baseline of levels of pro-inflammatory cytokines Interleukin-17 (IL-17), RANKL and Tumor Necrosis Factor (TNF)
timeFrame: Measured on weeks 0, 12, 24, and 48.
measure: Change from baseline in gut microflora
timeFrame: Measured on weeks 0, 12, 24, and 48.
measure: Change from baseline in dual-energy X-ray Absorptiometry (DXA) scans
timeFrame: Measured on weeks 0 and 48.
measure: Change from baseline in the Fracture Risk Assessment Tool (FRAX)
timeFrame: Measured on weeks 0 and 48.
measure: 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]).
timeFrame: Measured on weeks 0, 12, 24, and 48.
Locations:
city: Lake Worth
country: United States
facility: Altus Research
state: Florida
city: Port Saint Lucie
country: United States
facility: Health Awareness Inc.
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc.
state: Georgia
city: Henderson
country: United States
facility: Viable Research
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
Study officials:
References: