ANZCTR - Registration

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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]

None

Universal Trial Number (UTN)

Trial acronym

Probone21

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Osteopenia

Musculoskeletal

Condition category

Condition code

Diet and Nutrition

Other diet and nutrition disorders

Musculoskeletal

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]

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]

Any change in volumetric BMD at the tibia, measured by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) .

Timepoint [1]

12 months post-commencement of intervention

Secondary outcome [1]

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]

12 months post-commencement of intervention

Secondary outcome [2]

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]

12 months post-commencement of intervention

Secondary outcome [3]

Any change in calciotropic hormones that affect bone mineralization and bone mass (i.e. vitamin D, PTH, Calcitonin) assessed by plasma assay .

Timepoint [3]

12 months post-commencement of intervention

Secondary outcome [4]

Any change in C-reactive protein as a marker of inflammation as assessed by plasma assay.

Timepoint [4]

12 months post-commencement of intervention

Secondary outcome [5]

Any change in bone mineral density at lumbar spine, hip, forearm, whole body as measured by DXA.

Timepoint [5]

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]

Commercial sector/Industry

Name [1]

Probi AB

Address [1]

Probi AB
Ideongatan 1A
223 70 Lund
Sweden

Country [1]

Sweden

Primary sponsor type

University

Name

La Trobe University

Address

Plenty Rd &, Kingsbury Dr, Bundoora Victoria 3086

Country

Australia

Secondary sponsor category [1]

None

Name [1]

n/a

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

La Trobe Research - Human Research Ethics Committee

Ethics committee address [1]

Plenty Rd &, Kingsbury Dr, 
Bundoora VIC 3086

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

02/02/2021

Approval date [1]

08/03/2021

Ethics approval number [1]

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

A/Prof George Moschonis

Address

La Trobe University
Plenty Rd &, Kingsbury Dr,
Bundoora VIC 3086

Country

Australia

Phone

+61 3 9479 3482

Fax

Email

G.Moschonis@latrobe.edu.au

Contact person for public queries

Name

Stephanie Resciniti

Address

La Trobe University
Plenty Rd &, Kingsbury Dr,
Bundoora VIC 3086

Country

Australia

Phone

+61 456 701 341

Fax

Email

s.resciniti@latrobe.edu.au

Contact person for scientific queries

Name

George Moschonis

Address

La Trobe University
Plenty Rd &, Kingsbury Dr,
Bundoora VIC 3086

Country

Australia

Phone

+61 3 9479 3482

Fax

Email

G.Moschonis@latrobe.edu.au

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 - g.moschonis@latrobe.edu.au

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
10962	Informed consent form					381292-(Uploaded-03-05-2021-17-06-29)-Study-related document.docx

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.