ANZCTR - Registration

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

Trial registered on ANZCTR

Registration number

ACTRN12621001171808

Ethics application status

Approved

Date submitted

28/06/2021

Date registered

30/08/2021

Date last updated

17/01/2023

Date data sharing statement initially provided

30/08/2021

Type of registration

Prospectively registered

Titles & IDs

Public title

OsteoPreP: food supplements for postmenopausal bone health

Scientific title

OsteoPreP: The effect of probiotic supplementation on bone, muscle, and glucose metabolism in postmenopausal women: A randomised placebo-controlled trial

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

OsteoPreP

Linked study record

Health condition

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

bone loss

Condition category

Condition code

Musculoskeletal

Osteoporosis

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Participants will be randomized to one of the below arms and asked to consume the assigned supplement daily for a period of 12 months.
The active arm (probiotic capsule with prebiotic components [inulin]) and placebo control (magnesium stearate) will be taken twice daily.
• Probiotic treatment group (n = 80):
WBF-038; a proprietary formulation of the following strains: Akkermansia muciniphila, Clostridium butyricum, Clostridium beijerinckii, Anaerobutyricum hallii, Bifidobacterium infantis, plus chicory inulin and magnesium stearate. Exact doses will be disclosed after IP restrictions are met.
Adherence to the study supplementation will be recorded by participants checking a daily log/calendar for complete, partial and zero intake days.

Intervention code [1]

Prevention

Comparator / control treatment

Placebo Control group (n = 80): placebo capsules consisting of magnesium stearate - 1 capsule twice daily

Control group

Placebo

Outcomes

Primary outcome [1]

Relative change (%) in total volumetric bone density of the distal tibia measured using high resolution peripheral quantitative computed tomography (HR-pQCT)

Timepoint [1]

Baseline and 12 months

Secondary outcome [1]

Lumbar spine (L1-L4) bone mineral density (BMD) measured using dual energy X-ray absorptiometry (DXA)

Timepoint [1]

Baseline and 12 months

Secondary outcome [2]

Total hip BMD (DXA)

Timepoint [2]

Baseline and 12 months

Secondary outcome [3]

Tibia and radius trabecular bone volume fraction (HR-pQCT)

Timepoint [3]

Baseline and 12 months

Secondary outcome [4]

Tibia and radius cortical area (HR-pQCT)

Timepoint [4]

Baseline and 12 months

Secondary outcome [5]

Tibia and radius cortical volumetric BMD (HR-pQCT)

Timepoint [5]

Baseline and 12 months

Secondary outcome [6]

Total volumetric bone density of the distal radius (HRpQCT)

Timepoint [6]

Baseline and 12 months

Secondary outcome [7]

Serum bone turnover markers including procollagen type 1 N-terminal propeptide (P1NP), osteocalcin (OC), and C-terminal cross-linking telopeptide of type I collagen (ßCTX-I)

Timepoint [7]

Baseline, 6 and 12 months

Secondary outcome [8]

Short chain fatty acid (SCFA) stool levels (including butyrate)

Timepoint [8]

Baseline, 6 months, 12 months, and 2 weeks post intervention

Secondary outcome [9]

Stool gut microbiota composition

Timepoint [9]

Baseline, 6 months, 12 months, and 2 weeks post intervention

Secondary outcome [10]

Fasting blood glucose

Timepoint [10]

Baseline, 6 and 12 months

Secondary outcome [11]

Glycated haemoglobin (HbA1c) in blood

Timepoint [11]

Baseline, 6 and 12 months

Secondary outcome [12]

Lower leg muscle area (HR-pQCT)

Timepoint [12]

Baseline and 12 months

Secondary outcome [13]

Appendicular lean body mass (DXA)

Timepoint [13]

Baseline and 12 months

Secondary outcome [14]

Grip strength measured with hand dynamometer

Timepoint [14]

Baseline, 6 and 12 months

Secondary outcome [15]

High-sensitivity C-reactive protein (hs-CRP) in serum

Timepoint [15]

Baseline, 6 and 12 months

Secondary outcome [16]

Circulating number of regulatory T lymphocytes (Tregs) in blood

Timepoint [16]

Baseline and 12 months

Secondary outcome [17]

Oral glucose tolerance, assessed by OGTT

Timepoint [17]

Baseline, 6 and 12 months

Secondary outcome [18]

Muscle tissue composition (glycogen and triglyceride content, type 1 fibre proportion) from muscle biopsy

Timepoint [18]

Baseline, 6 and 12 months

Secondary outcome [19]

Lipocalin2 [intestinal inflammation] in stool

Timepoint [19]

Baseline, 6 months, 12 months and 2 weeks post intervention

Secondary outcome [20]

Cogstate (cognitive performance questionnaire)

Timepoint [20]

Baseline, 6 and 12 months

Secondary outcome [21]

Depression, anxiety and stress (DASS-21)

Timepoint [21]

Baseline, 6 and 12 months

Secondary outcome [22]

Gastrointestinal symptoms (GSRS)

Timepoint [22]

Baseline, 3, 6, 9 and 12 months

Secondary outcome [23]

Gut hormones (glucagon-like peptide 1 [GLP-1], peptide tyrosine-tyrosine [PYY]) and adiponectin in plasma

Timepoint [23]

Baseline, 6 and 12 months

Secondary outcome [24]

Quality of life (EQ-5D)

Timepoint [24]

Baseline, 6 and 12 months

Secondary outcome [25]

Social anxiety (SIAS)

Timepoint [25]

Baseline, 6 and 12 months

Secondary outcome [26]

Mental wellbeing (WEMWBS)

Timepoint [26]

Baseline, 6 and 12 months

Secondary outcome [27]

Blood glucose regulation (via continuous glucose monitoring)

Timepoint [27]

Baseline, 6 and 12 months

Secondary outcome [28]

Fasting blood insulin

Timepoint [28]

Baseline, 6 and 12 months

Secondary outcome [29]

Fat mass (DXA)

Timepoint [29]

Baseline and 12 months

Secondary outcome [30]

Blood metabolomics

Timepoint [30]

Baseline and 12 months

Secondary outcome [31]

Office blood pressure by sphygmomanometer

Timepoint [31]

Baseline, 6 and 12 months

Secondary outcome [32]

Pain intensity (VAS)

Timepoint [32]

Baseline, 6 and 12 months

Secondary outcome [33]

Calprotectin [intestinal inflammation] in stool

Timepoint [33]

Baseline, 6 months, 12 months and 2 weeks post intervention

Secondary outcome [34]

Muscle mass (DXA)

Timepoint [34]

Baseline and 12 months

Eligibility

Key inclusion criteria

• Postmenopausal women
• Caucasian (due to significant differences in BMD and bone remodeling between ethnicities)
• Between 1 and 4 years since final menses
• Signed informed consent
• Stated availability throughout the entire study period
• Mental ability to understand and willingness to fulfill all the details of the protocol
• 'Up to date' vaccination status
• Able to walk without the use of an aid

Minimum age

40 Years

Maximum age

65 Years

Sex

Females

Can healthy volunteers participate?

Yes

Key exclusion criteria

• Diagnosis of osteoporosis
• Low trauma fracture after 50 years of age
• T-score of -2.5 or less at the femoral neck or lumbar spine (L1-L4) on the DXA scan at screening visit
• HbA1c equal to or greater than 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)

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)

The randomisation list will be computer generated by the company providing the supplements. The company, as well as an independent external statistician, will also hold the key to unblind the study at the end. The probiotic supplement and placebo capsule bottles will be provided to the researchers pre-coded and blinded to the study group, where each bottle will be uniquely coded according to the randomisation list.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

A block randomisation (80 blocks; 2 participants per block) will be used to allocate participants to one of the two intervention arms. In addition, alternating blocks in the randomisation will be allocated to have circulating T lymphocytes counted, such that 50% of participants (40 blocks) will have this measure performed. The musculoskeletal subgroup analysis will comprise the first 30 participants (15 in each arm) that consent to the additional optional assessments of an OGTT, muscle biopsy, and ambulatory blood pressure.

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

All study participants' measurements will be analysed in a blinded manner. A complete data analysis plan of the primary and secondary study objectives will be drawn up prior to the completion of the study. Upon completion of the study, the data analysis plan will be sent to independent statistical consultants, along with the cleaned de-identified dataset which will be followed by the statistical analysis as per the predefined data analysis plan. Once the statistical analysis has been completed the randomisation list will be unlocked and the study arms unblinded.

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Categorical variables will be described by number and percentage and 95% confidence interval (CI) for percentages based on binomial distribution, and for continuous variables mean, standard deviation (SD), median, minimum and maximum, and 95% CI for the mean. Main comparisons will be made separately for the intervention (probiotic supplementation) vs. placebo. For tests between two groups with respect to dichotomous variables Fisher’s exact test will be used, and for continuous variables Fisher’s non-parametric permutation test will be used. The primary variable will be analysed as percent change from baseline to 12 months comparing the active treatment group with placebo. The study will be considered positive if the comparison vs placebo is significant at 0.05 significance level. The primary variable is expected to be normally distributed and analysis will be performed applying analysis of covariance (ANCOVA) with relative change from baseline to 12 months as dependent variable, treatment group as fixed effect and baseline value as covariate.
The difference in least square means with 95% CI for the treatment group vs placebo will be presented along with the associated p-value.
Secondary variables are all continuous and are not guaranteed to be normally distributed. For this reason, the change from baseline to 6 and 12 months will be tested by applying Fisher’s non-parametric permutation test. Mean difference between treatments will be presented along with the 95% CI based on the same permutation test. Primary and secondary analyses will be performed both for intention to treat (ITT) and per protocol (PP) population. The differences in parameter estimates between the intervention and the placebo will be evaluated for its clinical relevance. The secondary analyses will be considered exploratory and alpha of 0.05 will be applied with no further multiple adjustments.
Statistical power analysis was performed in relation to the primary outcome of relative 12-month change (%) in total volumetric bone density of the distal tibia, assessed using HR-pQCT. Based on a similar probiotic intervention in older women (Nilsson et al., 2018) the expected decline in tibia volumetric BMD is 1.85% in the placebo arm and 0.9% decrease at most in the treatment arm with a SD of 1.6%, an alpha of 0.05, 46 individuals are required in each arm to achieve > 80% power. However, in order to be able to detect smaller group-to-group differences and to account for a 20-30% attrition rate and due to multiple secondary outcomes, we will aim to recruit at least 80 individuals into each arm.

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

1/04/2022

Actual

1/04/2022

Date of last participant enrolment

Anticipated

30/06/2023

Actual

Date of last data collection

Anticipated

30/06/2024

Actual

Sample size

Target

160

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment postcode(s) [1]

3000 - Melbourne

Recruitment postcode(s) [2]

3001 - Melbourne

Recruitment postcode(s) [3]

3002 - East Melbourne

Recruitment postcode(s) [4]

3003 - West Melbourne

Recruitment postcode(s) [5]

3004 - Melbourne

Recruitment postcode(s) [6]

3006 - South Wharf

Recruitment postcode(s) [7]

3050 - Royal Melbourne Hospital

Recruitment postcode(s) [8]

3031 - Flemington

Recruitment postcode(s) [9]

3031 - Kensington

Recruitment postcode(s) [10]

3051 - North Melbourne

Recruitment postcode(s) [11]

3052 - Parkville

Recruitment postcode(s) [12]

3053 - Carlton

Recruitment postcode(s) [13]

3054 - Carlton North

Recruitment postcode(s) [14]

3057 - Brunswick East

Recruitment postcode(s) [15]

3056 - Brunswick

Recruitment postcode(s) [16]

3065 - Fitzroy

Recruitment postcode(s) [17]

3066 - Collingwood

Recruitment postcode(s) [18]

3067 - Abbotsford

Recruitment postcode(s) [19]

3068 - Clifton Hill

Recruitment postcode(s) [20]

3070 - Northcote

Recruitment postcode(s) [21]

3071 - Thornbury

Recruitment postcode(s) [22]

3101 - Kew

Recruitment postcode(s) [23]

3102 - Kew East

Recruitment postcode(s) [24]

3103 - Balwyn

Recruitment postcode(s) [25]

3104 - Balwyn North

Recruitment postcode(s) [26]

3121 - Richmond

Recruitment postcode(s) [27]

3122 - Hawthorn

Recruitment postcode(s) [28]

3123 - Hawthorn East

Recruitment postcode(s) [29]

3124 - Camberwell

Recruitment postcode(s) [30]

3141 - South Yarra

Recruitment postcode(s) [31]

3142 - Toorak

Recruitment postcode(s) [32]

3143 - Armadale

Recruitment postcode(s) [33]

3144 - Malvern

Recruitment postcode(s) [34]

3146 - Glen Iris

Recruitment postcode(s) [35]

3145 - Malvern East

Recruitment postcode(s) [36]

3181 - Prahran

Recruitment postcode(s) [37]

3182 - St Kilda

Recruitment postcode(s) [38]

3183 - Balaclava

Recruitment postcode(s) [39]

3184 - Elwood

Recruitment postcode(s) [40]

3185 - Elsternwick

Recruitment postcode(s) [41]

3186 - Brighton

Recruitment postcode(s) [42]

3205 - South Melbourne

Recruitment postcode(s) [43]

3206 - Albert Park

Recruitment postcode(s) [44]

3207 - Port Melbourne

Funding & Sponsors

Funding source category [1]

University

Name [1]

Australian Catholic University

Address [1]

115 Victoria Parade, Fitzroy VIC 3065

Country [1]

Australia

Primary sponsor type

University

Name

Australian Catholic University

Address

115 Victoria Parade, Fitzroy VIC 3065

Country

Australia

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

Pendulum Therapeutics, Inc.

Address [1]

933 20th Street
San Francisco, CA 94107

Country [1]

United States of America

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Australian Catholic University Human Research Ethics Committee

Ethics committee address [1]

8-20 Napier Street-Level 16, North Sydney NSW 2060

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/05/2021

Approval date [1]

27/09/2021

Ethics approval number [1]

Summary

Brief summary

Osteoporosis is a disease characterized by bone fragility resulting in bone fractures, which leads to increased morbidity and mortality. Following menopause, bone resorption exceeds bone formation, leading to net bone loss and bone fragility. There is an emerging body of evidence linking the gut microbiome and probiotic ingestion to skeletal, muscle, cognitive, and cardiometabolic function. The aim of this study is to investigate whether a taking a probiotic supplement .twice daily for 12 months positively impacts the rate of bone loss in recently psotmenopausal women

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 early postmenopausal women, aged 40-65 years. 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.

It is hypothesised that the probiotic supplementation will improve markers of bone health, muscle health, and metabolic health in postmenopausal women.

Trial website

Trial related presentations / publications

Public notes

To find out if you are eligible, please complete this short survey
https://rdcap.acu.edu.au/surveys/?s=MAERHHTDK3

Thank you!

Contacts

Principal investigator

Name

Prof Mattias Lorentzon

Address

Mary MacKillop Institute for Health Research
Level 5, 215 Spring St
Melbourne VIC 3000

Country

Australia

Phone

+61 3 92308056

Fax

[email protected]

Contact person for public queries

Name

Ms Alisa Turbic

Address

Mary MacKillop Institute for Health Research
Level 5, 215 Spring St
Melbourne VIC 3000

Country

Australia

Phone

+61 3 9953 3695

Fax

[email protected]

Contact person for scientific queries

Name

Prof Liesbeth Vandenput

Address

Mary MacKillop Institute for Health Research
Level 5, 215 Spring St
Melbourne VIC 3000

Country

Australia

Phone

+61 3 9230 8056

Fax

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Individual participant data will not be publicly communicated; only summary statistics and aggregated data to ensure personal data protection.

What supporting documents are/will be available?

No Supporting Document Provided

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.

Trial Review

Documents added manually

Documents added automatically