Clinical trial NCT05348694: OsteoPreP: Food Supplements for Postmenopausal Bone Health
Official title: OsteoPreP: The Effect of Probiotic Supplementation on Bone, Muscle, and Glucose Metabolism in Postmenopausal Women: A Randomised Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Postmenopausal Osteopenia
Bone Loss, Age Related
Age-Related Sarcopenia
Glucose Metabolism Disorders
Age-related Cognitive Decline
Keywords: Postmenopausal bone loss
Probiotics
Volumetric bone mineral density
Short-chain fatty acids
Lead sponsor: Australian Catholic University
Sponsor class: OTHER
Collaborators: name: Pendulum Therapeutics
name: Curtin University
First posted: 2022-04-27
Enrollment: 160
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized placebo-controlled trial
Primary purpose: PREVENTION

Brief summary: To evaluate the effect of 12 months of supplementation with a probiotic (probiotic plus prebiotic; 2 capsules per day) on relative change (%) in total volumetric bone density (measured using high resolution peripheral quantitative computed tomography \[HR-pQCT\]) of the distal tibia.

Detailed description: It is well established that bone loss occurs throughout life after the attainment of peak bone mass which is usually reached by the end of the second decade of life. During the first 5-8 years following menopause, women experience an accelerated bone loss, which is then followed by a slower phase of decline in bone mineral density (BMD). As over 40% of all women in Australia will suffer an osteoporotic (fragility) fracture in their lifetime, investigating interventions that can prevent bone loss in postmenopausal women is a critical focus. The menopausal transition is also associated with an increased risk of cardiovascular disease, diabetes, and cognitive decline. These conditions and their treatments can also affect bone health.

Previous research has indicated a potential link between the gut microbiome and bone health. Animal studies indicate that interventions affecting the gut microbiome may be successful in reducing bone loss, but human data is limited. Moreover, there is an emerging body of evidence linking the gut microbiome to cognitive, muscle and cardiometabolic function. Such studies indicate that probiotics (healthy gut bacteria) or prebiotics (food for healthy bacteria, e.g. fibre) can increase the amount of short chain fatty acids - such as butyrate -produced by the bacteria in the gut which may mediate the beneficial effects of improving gut health.

The proposed study is a double-blind, placebo-controlled randomised trial, which will investigate whether consuming a probiotic supplement containing inulin (a prebiotic soluble fibre) twice daily for 12 months will improve bone health in postmenopausal women. In addition, secondary outcomes will measure the effect of the intervention on immune system modulation and cognition as well as musculoskeletal and metabolic function as potential mediators.

One hundred and sixty postmenopausal women residing in Melbourne (Victoria, Australia) who are at least one year from their final menses will be recruited from the community via a mail out, advertisements in newspapers, social media, flyers as well as a landing page on an ACU managed website. The investigators have also applied for assisted mail outs through Services Australia for recruitment purposes. Services Australia is able to extract names and addresses of some target study demographics (females living in Melbourne aged between 40 and 65) from the Medicare database and mail them the study details on our behalf. Those wishing to participate will undergo a series of baseline assessments inclusive of bone mineral density scans, blood and stool sampling and physical activity and lifestyle questionnaires. They will then be randomised, in a blinded fashion, to consume one of the following two supplements:

* Placebo control group (n = 80): Placebo capsule - 2 capsules per day
* Probiotics group (n=80): Probiotic capsule - 2 capsules per day

Study outcomes will be measured at baseline, 6 months, and 12 months. In addition, participants will be contacted via the telephone and email at three-month and nine-month timepoints to report any adverse responses to the supplementation. At the 12-month time point, participants will cease supplementation and immediately (within 24 hours) attend a post intervention assessment and will complete identical assessment measures to those they did at baseline. Finally, at 2 weeks post supplementation cessation participants will be asked to attend an appointment to provide a final stool sample.

If it can be confirmed that long term consumption of a probiotic supplement can have beneficial effects on bone health, muscle health, and metabolic health in postmenopausal women, this intervention could be recommended in the prevention of osteoporosis and associated musculoskeletal and metabolic conditions.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women, 40-65 years old
* Caucasian (due to significant differences in BMD and bone remodelling between ethnicities)
* At least one year since final menses
* Signed informed consent
* Up to date Covid 19 vaccination status
* Able to walk without the use of an aid
* Stated availability throughout the entire study period
* Mental capacity to understand and willingness to fulfil all the details of the protocol
* Residing in Melbourne, Victoria, Australia

Exclusion Criteria:

* Diagnosis of osteoporosis
* T-score of -2.5 or less at the femoral neck or lumbar spine (L1-L4) on the DXA scan at screening visit
* HbA1c ≥6.5% at screening visit
* Blood pressure at screening visit of systolic \>180 mmHg and/or diastolic \>120 mmHg
* Untreated hyperthyroidism
* Rheumatoid arthritis
* Diagnosed with a disease-causing secondary osteoporosis or malabsorption: chronic obstructive pulmonary disease, inflammatory bowel disease, celiac disease, type 1/type 2 diabetes, or chronic liver disease
* Bariatric surgery
* Recently diagnosed malignancy (within the last 5 years)
* Current or recent oral corticosteroid use (any dose within the last 3 months, or 5mg of Prednisolone (or equivalent) or a higher daily dose for 14 days or more 3-12 months prior to screening)
* Use of antiresorptive therapy, including systemic hormone replacement therapy, bisphosphonates, strontium ranelate (current or during the last 3 years)
* Use of teriparatide (current or during the last 3 years)
* Participation in other clinical intervention trials
* Antibiotics treatment 2 months prior to inclusion
* Unwilling to cease taking other probiotic or prebiotic supplements (current use)

Primary outcomes:
measure: Total volumetric bone mineral density of the distal tibia
timeFrame: 12 months
Secondary outcomes:
measure: Bone mineral density of the lumbar spine
timeFrame: 12 months
measure: Bone mineral density of the hip
timeFrame: 12 months
measure: Tibia and radius trabecular bone volume
timeFrame: 12 months
measure: Tibia and radius cortical area
timeFrame: 12 months
measure: Tibia and radius cortical volumetric bone mineral density
timeFrame: 12 months
measure: Total volumetric bone mineral density of the distal radius
timeFrame: 12 months
measure: Serum C-terminal cross-linking telopeptide of type I collagen (ßCTX-I) - bone turnover marker
timeFrame: 6 months and 12 months
measure: Serum procollagen type 1 N-terminal propeptide (P1NP) - bone turnover marker
timeFrame: 6 months and 12 months
measure: Serum osteocalcin (OC) - bone turnover marker
timeFrame: 6 months and 12 months
measure: Short-chain fatty acids (SCFAs)
timeFrame: 6 months, 12 months, and 2 weeks post intervention
measure: 16s rRNA genetic sequencing of the gut microbiota
timeFrame: 6 months, 12 months, and 2 weeks post intervention
measure: Fasting blood glucose
timeFrame: 6 months and 12 months
measure: Glycated haemoglobin (HbA1c)
timeFrame: 6 months and 12 months
measure: Lower leg muscle area
timeFrame: 12 months
measure: Lean body mass
timeFrame: 12 months
measure: Grip strength
timeFrame: 6 months and 12 months
measure: High-sensitivity C-reactive protein (hs-CRP)
timeFrame: 6 months and 12 months
measure: Regulatory T lymphocytes (Tregs)
timeFrame: 12 months
measure: Oral glucose tolerance test (OGTT)
timeFrame: 6 months and 12 months
measure: Muscle tissue glycogen content
timeFrame: 6 months and 12 months
measure: Muscle tissue triglyceride content
timeFrame: 6 months and 12 months
measure: Muscle tissue type 1 fibre composition
timeFrame: 6 months and 12 months
measure: Lipocalin2
timeFrame: 6 months, 12 months, and 2 weeks post intervention
measure: Cogstate One back Test Cognitive performance test
timeFrame: 6 months and 12 months
measure: Cogstate Groton Maze Learning Test Cognitive performance test
timeFrame: 6 months and 12 months
measure: Cogstate Continuous Paired Associate Learning Test Cognitive performance test
timeFrame: 6 months and 12 months
measure: Cogstate Social Emotional Cognition Test Cognitive performance test
timeFrame: 6 months and 12 months
measure: Depression, Anxiety and Stress Scale 21
timeFrame: 6 months and 12 months
measure: Gastrointestinal Symptom Rating Scale
timeFrame: 6 months and 12 months
measure: Plasma glucagon-like peptide 1
timeFrame: 6 months and 12 months
measure: Plasma peptide tyrosine-tyrosine
timeFrame: 6 months and 12 months
measure: Plasma adiponectin
timeFrame: 6 months and 12 months
measure: EuroQol Five Dimensions Quality of life Medical Outcome Survey
timeFrame: 6 months and 12 months
measure: Social Interaction Anxiety Scale
timeFrame: 6 months and 12 months
measure: The Warwick-Edinburgh Mental Wellbeing Scale
timeFrame: 6 months and 12 months
measure: Continuous blood glucose level monitoring for 10 days
timeFrame: 6 months and 12 months
measure: Fasting blood insulin
timeFrame: 6 months and 12 months
measure: Fat mass
timeFrame: 12 months
measure: Blood metabolomics
timeFrame: 12 months
measure: Office blood pressure
timeFrame: 6 months and 12 months
measure: The Visual Analogue Scale Pain Intensity
timeFrame: 6 months and 12 months
measure: Calprotectin
timeFrame: 6 months, 12 months, and 2 weeks post intervention
measure: Muscle mass
timeFrame: 12 months
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Australian Catholic University
state: Victoria
Study officials:
affiliation: Australian Catholic University
name: John Hawley, PhD
role: PRINCIPAL_INVESTIGATOR
References: