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Trial registered on ANZCTR


Registration number
ACTRN12621000810819
Ethics application status
Approved
Date submitted
10/03/2021
Date registered
28/06/2021
Date last updated
17/09/2023
Date data sharing statement initially provided
28/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The effects of probiotics on bone loss/bone mineral density in early postemenopausal women
Scientific title
The effectiveness of a lactobacilli- based probiotic food supplement on bone metabolism and bone mineral density in Australian early postmenopausal women: A double- blind randomised placebo- controlled trial
Secondary ID [1] 303263 0
None
Universal Trial Number (UTN)
Trial acronym
Probone21
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Osteopenia 321009 0
Musculoskeletal
 321650 0
Condition category
Condition code
Diet and Nutrition 318814 318814 0 0
Other diet and nutrition disorders
Musculoskeletal 319397 319397 0 0
Osteoporosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention consists of capsules containing probiotic food supplement that combines a mix of selected probiotic bacteria (Lactobacillus - containing 10 billion CFU) in a dosage of one capsule daily for 12 months.
Intervention code [1] 319920 0
Prevention
Comparator / control treatment
The composition of the placebo capsule is a maltodextrin capsule with the same appearance, texture, taste and ingredients as the "intervention" but excluding the probiotic bacteria.
Control group
Placebo

Outcomes
Primary outcome [1] 326760 0
Any change in volumetric BMD at the tibia, measured by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) .
Timepoint [1] 326760 0
12 months post-commencement of intervention
Secondary outcome [1] 392595 0
Any change in biomarkers including bone formation markers (i.e. P1NP and total osteocalcin)
and bone resorption markers (i.e. CTx or TRAP 5b) as assessed by plasma assay,
Timepoint [1] 392595 0
12 months post-commencement of intervention
Secondary outcome [2] 392596 0
Any change in osteoclasts differentiation markers specifcally osteoprotegerin (OPG) levels and Receptoractivator of nuclear factor kappa ligand (RANKL) as assessed by plasma assay.
Timepoint [2] 392596 0
12 months post-commencement of intervention
Secondary outcome [3] 392597 0
Any change in calciotropic hormones that affect bone mineralization and bone mass (i.e. vitamin D, PTH, Calcitonin) assessed by plasma assay .
Timepoint [3] 392597 0
12 months post-commencement of intervention
Secondary outcome [4] 392599 0
Any change in C-reactive protein as a marker of inflammation as assessed by plasma assay.
Timepoint [4] 392599 0
12 months post-commencement of intervention
Secondary outcome [5] 396144 0
Any change in bone mineral density at lumbar spine, hip, forearm, whole body as measured by DXA.
Timepoint [5] 396144 0
12 months post-commencement of intervention

Eligibility
Key inclusion criteria
- Willingness to participate and availability throughout the study period
- 10-year major fracture risk (based on FRAX score) ranging from 5% in 45-year-old women to 15% in 65-year-old women.
- QUS heel BMD T-score greater than -2.5 standard deviation
- Early postmenopausal women, i.e. < 6 years since menopause
- Signed informed consent to participate to the study
Minimum age
45 Years
Maximum age
65 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- QUS heel BMD T-score less than or equal to -2.5 (i.e. potential presence of osteoporosis)
- Normal menstrual cycle or more than 6 years post menopause
- Younger than 45 years old and older than 65 years old.
- Medication that affects BMD
- Presence of disease: diabetes, untreated hyperthyroidism or hypothyroidism, hyperparathyroidism, impaired renal and liver function, malignancy diagnosed during the last 5 years, inflammatory bowel disease, celiac disease, chronic obstructive pulmonary disease, rheumatoid arthritis.
- Smoking or use of nicotine-containing products (currently or during the last six [6] months).
- Alcohol consumption more than 4 units per day.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation involved contacting the holder of the allocation schedule who was "off-site" or at central administration site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size calculation has been conducted with the use of G*Power version 3.1.9.2. Sample size estimation pointed to the need to recruit 50 study participants per treatment arm (statistical power 80%, probability of type I error 0.05). Expecting a drop-out rate of 20% from baseline to follow-up measurements, an additional sample of 24 study participants will have to be over-recruited, thus leading to total sample size of 124 (i.e. 62 per treatment arm).

General linear models (Repeated Measures Analysis of Variance) will be used to examine within group changes in the majority of primary and secondary outcome measures across all time points separately as well as between group differences for parametric data. Within-group changes will also be examined. All statistical analyses will be performed using the SPSS statistical analysis software for Windows (version 25.0).

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
19/07/2021
Actual
1/12/2021
Date of last participant enrolment
Anticipated
31/05/2023
Actual
20/06/2023
Date of last data collection
Anticipated
31/05/2024
Actual
Sample size
Target
124
Accrual to date
Final
114
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 307672 0
Commercial sector/Industry
Name [1] 307672 0
Probi AB
Country [1] 307672 0
Sweden
Primary sponsor type
University
Name
La Trobe University
Address
Plenty Rd &, Kingsbury Dr, Bundoora Victoria 3086
Country
Australia
Secondary sponsor category [1] 308369 0
None
Name [1] 308369 0
n/a
Address [1] 308369 0
Country [1] 308369 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307710 0
La Trobe Research - Human Research Ethics Committee
Ethics committee address [1] 307710 0
Plenty Rd &, Kingsbury Dr,
Bundoora VIC 3086
Ethics committee country [1] 307710 0
Australia
Date submitted for ethics approval [1] 307710 0
02/02/2021
Approval date [1] 307710 0
08/03/2021
Ethics approval number [1] 307710 0
HEC21038

Summary
Brief summary
Osteoporosis is a degenerative disease of the bone, which although occurs in older ages, has its roots in earlier life stages. Women are in general more susceptible to osteoporosis-related bone fractures than men, especially during the perimenopausal period, when the decrease in their oestrogen levels accelerates bone loss. Nevertheless, the increase of life expectancy in developed countries puts older men in a high risk of bone fractures too, especially after the age of 65 years.
The adequate intake of certain nutrients that are essential for bone metabolism, such as calcium and vitamin D, plays an important role in maintaining bone mass. As such, supplementation with calcium and/or vitamin D has been reported to exert a significant favourable effect on bone metabolism and bone mineral density (BMD). Nevertheless, the low-grade inflammation induced by a shift in the balance of gut bacterial composition has been reported to impair the absorption of dietary calcium and other important nutrients, while at the same time it seems to stimulate bone resorption through an accelerated activity of osteoclasts.
In this regard, it is now clear that the gut microbiome modulates bone haemostasis in mice, by regulating the immune system and osteoclast formation. The implication of this observation is that the modulation of the microbiome and/or inflammation may provide a new approach in the inhibition of age- and menopause-related bone loss and the prevention of osteoporosis.

Aim: The aim of the proposed study is to examine the effect of a 12-month supplementation with a probiotic supplement that combines three strains of Lactobacillus on bone metabolism as well as on volumetric and areal BMD in Australian early postmenopausal females, aged 45-65 years, with an increased risk for osteoporosis.
Trial website
probone.com.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108226 0
A/Prof George Moschonis
Address 108226 0
La Trobe University
Plenty Rd &, Kingsbury Dr,
Bundoora VIC 3086
Country 108226 0
Australia
Phone 108226 0
+61 3 9479 3482
Fax 108226 0
Email 108226 0
[email protected]
Contact person for public queries
Name 108227 0
Stephanie Resciniti
Address 108227 0
La Trobe University
Plenty Rd &, Kingsbury Dr,
Bundoora VIC 3086
Country 108227 0
Australia
Phone 108227 0
+61 456 701 341
Fax 108227 0
Email 108227 0
[email protected]
Contact person for scientific queries
Name 108228 0
George Moschonis
Address 108228 0
La Trobe University
Plenty Rd &, Kingsbury Dr,
Bundoora VIC 3086
Country 108228 0
Australia
Phone 108228 0
+61 3 9479 3482
Fax 108228 0
Email 108228 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data from questionnaires and biological samples that underlies published results
When will data be available (start and end dates)?
Immediately following publication and for 7 years after publication
Available to whom?
Only researchers who provide a methodologically sound proposal and justification of the request.
Available for what types of analyses?
Only to achieve the aims in the approved proposal.
How or where can data be obtained?
Upon request sent to chief investigator, A/Prof Moschonis who will approve access - [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10962Informed consent form    381292-(Uploaded-03-05-2021-17-06-29)-Study-related document.docx



Results publications and other study-related documents

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