Clinical trial NCT06375668: The Effect of the Probiotic Strains on Bone Mineral Density in Postmenopausal Women
Official title: The Effect of the Probiotic Strains Lactobacillus Plantarum and Lactobacillus Paracasei on Bone Mineral Density in Postmenopausal Women - a Multicenter Randomized Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Osteoporosis, Postmenopausal
Bone Density, Low
Keywords: bone mineral density
osteoporosis
probiotics
Lead sponsor: Nordic Biotic Sp. z o.o.
Sponsor class: INDUSTRY
First posted: 2024-04-19
Enrollment: 170
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Osteoporosis is a systemic condition characterized by low bone mass and altered bone tissue microarchitecture, with the resulting greater bone fragility leading to fractures. Osteoporosis develops as a result of genetic and environmental factors, with the patient's lifestyle playing an important role. Recent years saw an emergence of reports on the significance of the intestinal microbiota in the development of osteoporosis, thus new ways of modifying the composition and activity of microbiota have been sought, and the potential role of probiotics has been considered. Probiotics are defined as live microorganisms, which-when administered at appropriate doses-are beneficial to the host's health. Probiotics both modify the gut microbiota composition and directly affect the human body. Recently published clinical studies demonstrated that probiotics may facilitate osteoporosis treatment and prevention. The current randomized double-blind placebo-controlled study will assess the effect of a dietary intervention via oral supplementation of Lactobacillus plantarum and Lactobacillus paracasei in a population of Polish postmenopausal women on their bone mineral density assessed via bone densitometry-derived T-scores of the lumbar segment of the spine (L1-L4). Study subjects will take the provided probiotic formulation/placebo orally once daily for 12 months.

Detailed description: The main purpose of the study is to assess the effect of oral probiotic supplementation on bone mineral density in postmenopausal women. A total of 170 female subjects who meet all the inclusion criteria and none of the exclusion criteria are to be included and randomized to one of two arms (the probiotic arm or the placebo arm) at a ratio of 1:1.

The subjects who provide their written informed consent will receive oral probiotic formulation containing a mixture of two strains Lactobacillus plantarum and Lactobacillus paracasei or placebo. The probiotic formulation and placebo will be provided by Nordic Biotic Ltd. (the company will also ensure study drug blinding). Study subjects will take the provided probiotic formulation/placebo orally once daily for 12 months.

The study timeline spans 54 weeks and involves 13 visits, including:

1. Screening visit - subjects eligibility to participate in the study will be assessed based on the inclusion/exclusion criteria - the screening period will last up to 14 before the study drug is administered;
2. Randomization visit (visit 0) - subjects will be randomly allocated to study groups and will receive a supply of the study probiotic or placebo;
3. 6 office visits (at months 2, 4, 6, 8, 10, and 12 of visit 0);
4. 5 remote visits (at months 1, 3, 7, 9, and 11 of visit 0).

All subjects included in the study will undergo:

* History-taking and physical examination at each office visit,
* Nutritional status assessment (measurements of body weight and height, with a BMI calculation) at the screening visit and at months 6 and 12 of the study intervention,
* Two densitometry scans (DEXA) of the lumbar segment of the spine (L1-L4) at the screening visit and at month 12 of visit 0,
* Treatment satisfaction assessment (treatment satisfaction questionnaire) at months 2, 6, 10, and 12 of the study intervention.

At each visit, whether conducted at the doctor's office or remotely, subjects will be asked about their use of the study drug and any gastrointestinal symptoms (number of bowel movements, stool consistency, bloating, abdominal pain), and the use of any other medications (including antibiotics). Each time, the subjects will be also asked about any side effects. Stool consistency will be assessed with the Bristol Stool Form Scale, and abdominal pain, bloating, and nausea will be assessed with a 5-grade Likert scale.

Blood samples will be collected from all subjects during the screening period, after 6 months of intervention and at the completion of intervention (i.e. at month 12).

The following blood tests will be conducted:

1. Complete blood count, erythrocyte sedimentation rate, and C-reactive protein levels (at screening and at months 6 and 12 of the study intervention);
2. Serum calcium, phosphorus, and alkaline phosphatase levels (at screening and at months 6 and 12 of the study intervention);
3. Serum vitamin D and parathormone levels (at screening and at month 12 of intervention).

Eligibility criteria: Inclusion Criteria:

1. Postmenopausal women (between 2 and 5 years after their last menstrual period)
2. A dual-energy X-ray absorptiometry (DEXA) scan-based T-score of the lumbar spine (L1-L4) of less than -1.49 (i.e. a normal value according to the World Health Organization)
3. Body mass index (BMI) between 18 and 30
4. Vitamin 25 (OH)D levels between 31-50 ng/mL

Exclusion Criteria:

1. The last menstrual period less than 2 or more than 5 years before study recruitment
2. BMI under 18 or above 30
3. Oral or transdermal hormone therapy with estrogens and/or progestogens within the last 6 months
4. Corticosteroid or thyroid hormone therapy within the last 6 months
5. History of osteopenia or osteoporosis
6. Neoplastic disease treated with cytostatic agents within the last 12 months
7. Autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis; malabsorption syndromes, including celiac disease; chronic kidney disease; chronic liver failure; endocrine disorders, including Hashimoto thyroiditis, Graves' disease, Cushing disease or syndrome, hyperparathyroidism, hypogonadism, hyperprolactinemia, acromegaly, diabetes mellitus; and other chronic conditions affecting bone metabolism
8. Antibiotic therapy within the last 2 months prior to study recruitment
9. Probiotic use within the last 2 months prior to study recruitment
10. Calcium and vitamin D supplementation within the 2 months prior to study recruitment
11. Treatment with antidepressant or antipsychotic agents involving a change of the agents or dosage within the last 3 months
12. Substance use disorder (alcohol, drugs, nicotine)
13. History of organ transplantation
14. Exposure to the SARS-Cov-2 virus within 14 days prior to study recruitment (based on patient declaration)
15. An acute COVID-19 infection within 14 days prior to study recruitment (based on patient declaration)
16. A surgical procedure scheduled to take place during this study
17. Participation in another study within the last 6 months
18. Inability to give an informed consent in writing
19. Any disease or circumstances that, according to the Investigator or Sponsor, might prevent the subject from completing the study or following study procedures and requirements

Primary outcomes:
measure: The effect of intervention on bone mineral density
timeFrame: From baseline and after 12 months of intervention
Secondary outcomes:
measure: Changes in the level of calcium
timeFrame: From baseline and after 6 and 12 months of intervention
measure: Changes in the level of phosphorus
timeFrame: From baseline and after 6 and 12 months of intervention
measure: Changes in the level of alkaline phosphatase
timeFrame: From baseline and after 6 and 12 months of intervention
measure: Changes in the level of vitamin D
timeFrame: From baseline and after 12 months of intervention
measure: Changes in the level of C-reactive protein
timeFrame: From baseline and after 6 and 12 months of intervention
measure: Changes in Body Mass Index (BMI)
timeFrame: From baseline and after 6 and 12 months of intervention
measure: Changes in type of stools
timeFrame: From baseline for 12 months of intervention in 1 month intervals
measure: Changes in the number of bowel movements
timeFrame: From baseline for 12 months of intervention in 1 month intervals
measure: Changes in severity of abdominal pain
timeFrame: From baseline for 12 months of intervention in 1 month intervals
measure: Changes in severity of bloating
timeFrame: From baseline for 12 months of intervention in 1 month intervals
measure: Occurrence of adverse events
timeFrame: For 12 months of intervention in 1 month intervals
measure: Satisfaction with the intervention
timeFrame: At months 2, 6, 10, and 12 of the intervention
Other outcomes:
Locations:
city: Bytom
country: Poland
facility: Private Specialist Practice
city: Katowice
country: Poland
facility: Specialist Practice
city: Poznań
country: Poland
facility: Clinical Research Center
Study officials:
affiliation: Private Specialist Practice
name: Joanna Głogowska-Szeląg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: