Prevention of Glucocorticoid Induced Impairment of Bone Metabolism

• Status: Not yet recruiting
• Trial end date: 2022-02-01
• Target enrollment: 0
• Participant gender: All

Summary

Glucocorticoid (GC) therapy is used to treat a variety of inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, bronchial asthma, allergies, ankylosing spondylitis and some forms of cancers. Despite the well-known side-effects, GC treatment is widely used. Oral GC therapy leads to a rapid and profound effects on bone metabolism, with increased osteoblast apoptosis and prolonged osteoclast survival, which increases bone resorption, resulting in bone loss, and a subsequent increased fracture risk. Within days of high dose oral GC, glucose tolerance decreases and bone turnover is shifted in favour of less bone formation and increased bone resorption. Bone formation and bone resorption can be estimated by measuring serum bone turnover markers.

The gut microbiota is involved in regulating bone metabolism and recently it was demonstrated that Lactobacillus reuteri 6475 (LR) could reduce bone loss over 12 months by half in older women. In a recent experimental study, it was discovered that mice treated either with broad spectrum antibiotics, eradicating gut microbiota, or with LR did not experience GC induced bone loss in the spine and femur. L. reuteri has been widely studied in clinical trials and has been shown to have probiotic, health-promoting effects in both adults and children.

The aim of this planned randomized, double-blind, placebo-controlled trial is to investigate if daily supplementation with LR, compared to placebo, can prevent the negative effects of oral glucocorticoid (GC) on bone turnover and on blood glucose regulation in healthy young adult men and women.

If LR is able to prevent deleterious side effects, such as bone loss and impaired glucose tolerance, of oral GC treatment, the probiotic could potentially be recommended and used to improve health in a substantial yearly number of patients treated with GC.

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Sahlgrenska University Hospital, Sweden
• Collaborator: BioGaia AB
• Treatments: Prednisolone

Criteria

Inclusion Criteria:

• Healthy men and women, 18-45 years old.

• Stated availability throughout the entire study period.

• Ability to understand study instructions and willingness to adhere to the protocol.

• Signed informed consent.

• Vaccinated for Covid-19

Exclusion Criteria:

• History of diabetes or glucose intolerance, defined as an abnormal oral glucose tolerance test (OGTT).

• Obesity, BMI>30 kg/m2

• History of adrenal disease or impairment.

• Previous (within the last 5 years) or current use of antiresorptive therapy, including systemic hormone therapy (estrogen), bisphosphonates, strontium ranelate or denosumab.

• 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.

• Untreated hyperthyroidism or hyperthyroidism within the last 5 years.

• Known untreated hyperparathyroidism.

• Rheumatoid arthritis.

• 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).

• 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.

• Oral corticosteroid use.

• History of peptic ulcer.

• Diagnosed osteoporosis.

• Current smoking or other use of nicotine containing products.

• Pregnancy.