Postmenopausal OsteoporosisELBOWIINCT04169789
Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri
A study testing Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475) in people with Postmenopausal Osteoporosis, run by Sahlgrenska University Hospital at 1 site in Sweden.
Trial summary
This study evaluates the effect of two different doses of Lactobacillus reuteri ATCC PTA 6475 (L.reuteri 6475) on bone loss in early postmenopausal women. One third of the participants will be randomised to the lower dose, one third to the higher dose and one third to placebo. Read more about this study
- Who is it for?
- Ages 45 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Postmenopausal Osteoporosis
- What is being tested?
- Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 239 participants
- Where
- 1 siteSweden
- Study dates
- 4 Dec 2019to 18 Oct 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Postmenopausal women, 45 years or older, within 1-4 years from their last menses.
- Vitamin D levels above 25 nmol/L.
- Signed informed consent.
- Stated availability throughout the entire study period.
- Ability to understand study instructions and willingness to adhere to the protocol.
Who cannot join
- Bone mineral density of < -2.5 combined with a fracture risk assessment tool (FRAX) score of 20% or higher for major osteoporotic fracture.
- Severe osteoporosis, defined as bone mineral density of < -3.0 in either the total hip, femur neck or lumbar spine L1-L4.
- Vertebral fracture (grade II or III) diagnosed using lateral spine imaging with DXA.
- Untreated hyperthyroidism or hyperthyroidism within the last 5 years.
- Known untreated hyperparathyroidism.
- Rheumatoid arthritis.
Show all 19Show fewer
- Diagnosed with disease causing secondary osteoporosis, including chronic obstructive pulmonary disease, inflammatory bowel disease, celiac disease, or diabetes mellitus.
- Recently diagnosed malignancy (within the last 5 years).
- Oral corticosteroid use.
- Previous (within the last 5 years) use of antiresorptive therapy, including systemic hormone therapy (estrogen), bisphosphonates, strontium ranelate or denosumab.
- Systemic skeletal disease (including e.g. Paget's disease and osteogenesis imperfecta).
- Any systemic disease that could affect bone loss, as judged by the investigator.
- Use of teriparatide (current or during the last 3 years).
- Participation in other clinical trials.
- Current antibiotics treatment or within the last 2 months prior to inclusion.
- Current and within the past 2 months use of probiotic supplement
- Vitamin D deficiency (25-OH vitamin D<25 nmol/l)
- Hypo- or hypercalcemia.
- Osteosynthesis materials in both lower legs (tibia).
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Geriatric Medicine, Sahlgrenska University Hospital, Mölndal
Gothenburg, Västra Götaland County, 43180
About this study
Official title: Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri - A Randomized, Placebo-Controlled, Single Centre Clinical Trial
This study evaluates the effect of two different doses of Lactobacillus reuteri ATCC PTA 6475 (L.reuteri 6475) on bone loss in early postmenopausal women. One third of the participants will be randomised to the lower dose, one third to the higher dose and one third to placebo.
Read the detailed description
We have previously shown that daily supplementation of the probiotic Lactobacillus reuteri ATCC PTA 6475 (10E10 colony-forming units (CFU)) was able to reduce bone loss over 12 months in 76-year-old women compared to placebo.
It is not known if the probiotic is effective over longer time periods or if the effect is dose-dependent. The aim of this study is to investigate if two different doses of Lactobacillus reuteri ATCC PTA 6475 (total daily dose of either 1x10E9 or 1x10E10 CFU/day) can prevent or reduce bone loss, compared to placebo, in early (1-4 years since last menses) postmenopausal women over 24 months. All women will receive 400 IU of vitamin D (cholecalciferol) per day. Changes in bone mineral density, bone geometry and microstructure will be measured using dual x-ray absorptiometry and high resolution peripheral computed tomography.
- Conditions
- Postmenopausal Osteoporosis
- Being tested
- Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)
- Medical subject headings
- Osteoporosis, Postmenopausal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)Dietary supplement
L.reuteri high or low dose with cholecalciferol compared to cholecalciferol only.
| Study group | Role | What they receive |
|---|---|---|
| L. reuteri Low Dose | Active comparator | Capsules of freeze-dried L. reuteri 6475 of 5x10E8 colony-forming units (CFU) mixed with maltodextrin powder and 200 IU of cholecalciferol, taken twice daily for 24 months, yielding a total dose of either 1x10E9 L.reuteri CFU and 400 IU of cholecalciferol per day. Receives: Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475) |
| L. reuteri High Dose | Active comparator | Capsules of freeze-dried L. reuteri 6475 of 5x10E9 colony-forming units (CFU) mixed with maltodextrin powder and 200 IU of cholecalciferol, taken twice daily for 24 months, yielding a total daily dose of 1x10E10 L.reuteri CFU and 400 IU of cholecalciferol per day. Receives: Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475) |
| Placebo | Placebo comparator | Placebo product identical to the active product (L. reuteri) in taste and appearance but without the active component, orally twice daily, for 24 months.The placebo product contains 200 IU cholecalciferol per dose, yielding a total dose of cholecalciferol of 400 IU per day. Receives: Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total tibia volumetric bone mineral density
Measured using high resolution peripheral computed tomography (HRpQCT), relative change 0-24 months
Measured: 24 months
Secondary outcomes (12)
Areal bone mineral density (aBMD) at the lumbar spine
Measured using dual x-ray absorptiometry (DXA), relative change 0-24 months and 0-12 months
Measured: 24 months
Areal BMD of the total hip (DXA)
Measured using DXA, relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Tibia trabecular bone volume fraction
Measured using HRpQCT, relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Tibia cortical area
Measured using HRpQCT, relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Tibia cortical volumetric BMD
Measured using HRpQCT, relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Total tibia volumetric bone mineral density
Measured using HRpQCT, relative change 0-12 months
Measured: 12 months
Blood bone formation marker procollagen type 1N propeptide (P1NP)
Relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Blood bone resorption marker C-terminal cross-linking telopeptide of type I collagen (CTX)
Relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Fecal calprotectin
Relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Fecal lipocalin-2
Relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Serum butyrate concentration
Relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Serum Wnt10b concentration
Relative change 0-24 months and 0-12 months
Measured: 0-24 months and 0-12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2019
- Study start4 Dec 2019
- Primary completion18 Oct 2022
- Study completion18 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Postmenopausal OsteoporosisStudies of the same condition, open and under way.
- More trials run by Sahlgrenska University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 239 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- BioGaia AB
- Responsible party
- Principal investigator, Mattias Lorentzon, Sahlgrenska University Hospital
- Investigators
- Mattias Lorentzon, MD, PhD, Principal investigator, Sahlgrenska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04169789
- Sponsor's protocol ID
- ELBOWII
- Acronym
- ELBOWII
- Status last verified
- Feb 2023
- First submitted
- 18 Nov 2019
- Last updated
- 6 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nilsson AG, Sundh D, Backhed F, Lorentzon M. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018 Sep;284(3):307-317. doi: 10.1111/joim.12805. Epub 2018 Jul 22.
PubMed 29926979Gregori G, Pivodic A, Magnusson P, Johansson L, Hjertonsson U, Brattemark E, Lorentzon M. Limosilactobacillus reuteri 6475 and Prevention of Early Postmenopausal Bone Loss: A Randomized Clinical Trial. JAMA Netw Open. 2024 Jun 3;7(6):e2415455. doi: 10.1001/jamanetworkopen.2024.15455.
PubMed 38865129
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri - A Randomized, Placebo-Controlled, Single Centre Clinical Trial
- ClinicalTrials.gov ID
- NCT04169789
- Acronym / sponsor ID
- ELBOWII / ELBOWII
- Conditions
- Postmenopausal Osteoporosis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 239 participants (actual)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Collaborators
- BioGaia AB
- Study start
- 4 Dec 2019 (actual)
- Primary completion
- 18 Oct 2022 (actual)
- Study completion
- 18 Oct 2022 (actual)
- First posted
- 20 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the effect of two different doses of Lactobacillus reuteri ATCC PTA 6475 (L.reuteri 6475) on bone loss in early postmenopausal women. One third of the participants will be randomised to the lower dose, one third to the higher dose and one third to placebo.
Detailed description
We have previously shown that daily supplementation of the probiotic Lactobacillus reuteri ATCC PTA 6475 (10E10 colony-forming units (CFU)) was able to reduce bone loss over 12 months in 76-year-old women compared to placebo.
It is not known if the probiotic is effective over longer time periods or if the effect is dose-dependent. The aim of this study is to investigate if two different doses of Lactobacillus reuteri ATCC PTA 6475 (total daily dose of either 1x10E9 or 1x10E10 CFU/day) can prevent or reduce bone loss, compared to placebo, in early (1-4 years since last menses) postmenopausal women over 24 months. All women will receive 400 IU of vitamin D (cholecalciferol) per day. Changes in bone mineral density, bone geometry and microstructure will be measured using dual x-ray absorptiometry and high resolution peripheral computed tomography.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| L. reuteri Low Dose | Active comparator | Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)Capsules of freeze-dried L. reuteri 6475 of 5x10E8 colony-forming units (CFU) mixed with maltodextrin powder and 200 IU of cholecalciferol, taken twice daily for 24 months, yielding a total dose of either 1x10E9 L.reuteri CFU and 400 IU of cholecalciferol per day. |
| L. reuteri High Dose | Active comparator | Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)Capsules of freeze-dried L. reuteri 6475 of 5x10E9 colony-forming units (CFU) mixed with maltodextrin powder and 200 IU of cholecalciferol, taken twice daily for 24 months, yielding a total daily dose of 1x10E10 L.reuteri CFU and 400 IU of cholecalciferol per day. |
| Placebo | Placebo comparator | Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)Placebo product identical to the active product (L. reuteri) in taste and appearance but without the active component, orally twice daily, for 24 months.The placebo product contains 200 IU cholecalciferol per dose, yielding a total dose of cholecalciferol of 400 IU per day. |
Who may qualify
- Ages
- 45 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Postmenopausal women, 45 years or older, within 1-4 years from their last menses.
- Vitamin D levels above 25 nmol/L.
- Signed informed consent.
- Stated availability throughout the entire study period.
- Ability to understand study instructions and willingness to adhere to the protocol.
Key exclusion criteria (19 listed)
- Bone mineral density of < -2.5 combined with a fracture risk assessment tool (FRAX) score of 20% or higher for major osteoporotic fracture.
- Severe osteoporosis, defined as bone mineral density of < -3.0 in either the total hip, femur neck or lumbar spine L1-L4.
- Vertebral fracture (grade II or III) diagnosed using lateral spine imaging with DXA.
- Untreated hyperthyroidism or hyperthyroidism within the last 5 years.
- Known untreated hyperparathyroidism.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475)L.reuteri high or low dose with cholecalciferol compared to cholecalciferol only. | Dietary supplement | L. reuteri High Dose, L. reuteri Low Dose, Placebo |
Primary outcome
Total tibia volumetric bone mineral density
Time frame: 24 months
Measured using high resolution peripheral computed tomography (HRpQCT), relative change 0-24 months
12 secondary outcomes
Areal bone mineral density (aBMD) at the lumbar spine
Time frame: 24 months
Areal BMD of the total hip (DXA)
Time frame: 0-24 months and 0-12 months
Tibia trabecular bone volume fraction
Time frame: 0-24 months and 0-12 months
Tibia cortical area
Time frame: 0-24 months and 0-12 months
Tibia cortical volumetric BMD
Time frame: 0-24 months and 0-12 months
Total tibia volumetric bone mineral density
Time frame: 12 months
Blood bone formation marker procollagen type 1N propeptide (P1NP)
Time frame: 0-24 months and 0-12 months
Blood bone resorption marker C-terminal cross-linking telopeptide of type I collagen (CTX)
Time frame: 0-24 months and 0-12 months
Fecal calprotectin
Time frame: 0-24 months and 0-12 months
Fecal lipocalin-2
Time frame: 0-24 months and 0-12 months
Serum butyrate concentration
Time frame: 0-24 months and 0-12 months
Serum Wnt10b concentration
Time frame: 0-24 months and 0-12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- Background: PubMed 29926979Nilsson AG, Sundh D, Backhed F, Lorentzon M. Lactobacillus reuteri reduces bone loss in older women with low bone mineral density: a randomized, placebo-controlled, double-blind, clinical trial. J Intern Med. 2018 Sep;284(3):307-317. doi: 10.1111/joim.12805. Epub 2018 Jul 22.
- Derived from this study: PubMed 38865129Gregori G, Pivodic A, Magnusson P, Johansson L, Hjertonsson U, Brattemark E, Lorentzon M. Limosilactobacillus reuteri 6475 and Prevention of Early Postmenopausal Bone Loss: A Randomized Clinical Trial. JAMA Netw Open. 2024 Jun 3;7(6):e2415455. doi: 10.1001/jamanetworkopen.2024.15455.
- Individual participant dataSharing planned: No
Related trials for Postmenopausal Osteoporosis
Active, not recruitingObservational study
The Impact of Osteosarcopenia on Falls, Kinesiophobia, and Quality of Life in Postmenopausal Women
Osteosarcopenia, Sarcopenia
Not yet recruitingPhase 4
Romosozumab and Denosumab Combination Therapy for Osteoporosis
Postmenopausal Osteoporosis
Not yet recruiting
Effects of Sensorimotor Balance Training vs Digitally Augmented Core Stabilization in Women With Osteoporosis
Postmenopausal Osteoporosis
Active, not recruitingPhase 4
Abaloparatide Added to Ongoing Denosumab vs Continued Denosumab Alone
Osteoporosis, Postmenopausal
RecruitingPhase 4
Combined Anabolic Therapy
Osteoporosis, Postmenopausal, Osteoporosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mattias Lorentzon, MD, PhD principal investigator
Sahlgrenska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475) in people with Postmenopausal Osteoporosis, run by Sahlgrenska University Hospital at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total tibia volumetric bone mineral density (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04169789, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.