OsteoPreP: Food Supplements for Postmenopausal Bone Health

NCT ID: NCT05348694

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2025-04-30

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.

Conditions

Postmenopausal Osteopenia; Bone Loss, Age Related; Age-Related Sarcopenia; Glucose Metabolism Disorders; Age-related Cognitive Decline

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: TRIPLE

Study Groups

Pendulum WBF-038

Pendulum 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 - 1 capsule with the morning meal and 1 capsule with the evening meal for 12 months.

Group Type: ACTIVE_COMPARATOR

Pendulum WBF-038

Intervention Type: DIETARY_SUPPLEMENT

All bacteria contained in Pendulum WBF-038 are commensal organisms that have been repeatedly documented to inhabit the human gastrointestinal tract under normal circumstances. Pendulum's WBF-038 is a proprietary formulation of the following strains: Akkermansia muciniphila, Clostridium butyricum, Clostridium beijerinckii, Anaerobutyricum hallii, Bifidobacterium infantis, plus chicory inulin and magnesium stearate. The organisms were grown under controlled conditions consistent with Good Manufacturing Practices (GMP) and employ no animal-derived products. All ingredients utilized during manufacturing were food grade and qualified as generally recognized as safe (GRAS).

The product is provided as acid-resistant capsules in bottles that are to be stored refrigerated at 4℃.

Pendulum Placebo

Pendulum Placebo containing Magnesium stearate - 1 capsule with the morning meal and 1 capsule with the evening meal for 12 months.

Group Type: PLACEBO_COMPARATOR

Pendulum Placebo

Intervention Type: DIETARY_SUPPLEMENT

Pendulum placebo capsules containing magnesium stearate

Interventions

Pendulum WBF-038

All bacteria contained in Pendulum WBF-038 are commensal organisms that have been repeatedly documented to inhabit the human gastrointestinal tract under normal circumstances. Pendulum's WBF-038 is a proprietary formulation of the following strains: Akkermansia muciniphila, Clostridium butyricum, Clostridium beijerinckii, Anaerobutyricum hallii, Bifidobacterium infantis, plus chicory inulin and magnesium stearate. The organisms were grown under controlled conditions consistent with Good Manufacturing Practices (GMP) and employ no animal-derived products. All ingredients utilized during manufacturing were food grade and qualified as generally recognized as safe (GRAS).

The product is provided as acid-resistant capsules in bottles that are to be stored refrigerated at 4℃.

Intervention Type: DIETARY_SUPPLEMENT

Pendulum Placebo

Pendulum placebo capsules containing magnesium stearate

Intervention Type: DIETARY_SUPPLEMENT

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)

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Pendulum Therapeutics

INDUSTRY

Sponsor Role: collaborator

Curtin University

OTHER

Sponsor Role: collaborator

Australian Catholic University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

John Hawley, PhD

Role: PRINCIPAL_INVESTIGATOR

Australian Catholic University

Locations

Australian Catholic University

Melbourne, Victoria, Australia

Countries

Australia

References

Turbic A, Vandenput L, Gandham A, Lorentzon M. Effects of Synbiotic Supplementation on Bone and Metabolic Health in Caucasian Postmenopausal Women: Rationale and Design of the OsteoPreP Trial. Nutrients. 2024 Dec 6;16(23):4219. doi: 10.3390/nu16234219.

Reference Type: DERIVED

PMID: 39683612 (View on PubMed)

Other Identifiers

2021-122HC

Identifier Type: -

Identifier Source: org_study_id