Prevention of Glucocorticoid Induced Impairment of Bone Metabolism

NCT04767711 | Completed

• 1 other identifier: GCreuteri
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bone Loss

Outcome Measures

Primary Outcomes (3)

• Change in bone turnover marker serum osteocalcin

  Between group percent change in bone turnover markers osteocalcin between baseline (day 16, prior to GC treatment start) and day 23 (7 days after starting oral GC).

  Baseline (day 16) to day 23

• Change in bone turnover marker serum PINP

  Between group percent change in bone turnover markers serum PINP between baseline (day 16, prior to GC treatment start) and day 23 (7 days after starting oral GC).

  Baseline (day 16) to day 23

• Change in bone turnover marker serum CTX

  Between group per cent change in bone turnover marker serum CTX between baseline (day 16, prior to GC treatment start) and day 23 (7 days after starting oral GC).

  Baseline (day 16) to day 23

Secondary Outcomes (7)

• Change in blood glucose levels

  Day 14-16 to day 16-23

• Change in serum marker of intestinal permeability - endotoxin levels

  Baseline (day 16) to day 23

• Change in feces marker lipocalin-2 of intestinal inflammation

  Baseline (day 16) and day 23

• Change in feces marker calprotectin of intestinal inflammation

  Baseline (day 16) and day 23

• Change in serum marker lipocalin-2 of intestinal inflammation

  Baseline (day 16) and day 23

Study Arms (2)

L. reuteri

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 30 days, yielding a total daily dose of 1x10E10 L.reuteri CFU and 400 IU of cholecalciferol per day. Oral glucocorticoid 25 mg daily for 7 days.

Dietary Supplement: Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475); Drug: Prednisolone

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 30 days.The placebo product contains 200 IU cholecalciferol per dose, yielding a total dose of cholecalciferol of 400 IU per day. Oral glucocorticoid 25 mg daily for 7 days.

Drug: Prednisolone

Interventions

Lactobacillus reuteri ATCC PTA 6475 (L. reuteri 6475) DIETARY_SUPPLEMENT

L.reuteri with cholecalciferol compared to cholecalciferol only.

L. reuteri

Prednisolone DRUG

Oral glucocorticoid 25 mg daily for 7 days.

L. reuteri; Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Sahlgrenska University Hospital: lead
• BioGaia AB: collaborator

Study Sites (1)

Geriatric Medicine, Sahlgrenska University Hospital

Mölndal, 43180, Sweden

Location

Related Publications (2)

• 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.

  PMID: 29926979 BACKGROUND

• Gregori G, Johansson L, Silberberg L, Imberg H, Magnusson P, Lind M, Lorentzon M. Prevention of glucocorticoid-induced impairment of bone metabolism-a randomized, placebo-controlled, single centre proof-of-concept clinical trial. JBMR Plus. 2025 Feb 17;9(4):ziaf031. doi: 10.1093/jbmrpl/ziaf031. eCollection 2025 Apr.

  PMID: 40162303 DERIVED

MeSH Terms

Conditions

Bone Diseases, Metabolic

Interventions

Prednisolone

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Mattias Lorentzon, MD, PhD

  Sahlgrenska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Study Record Dates

• First Submitted: February 12, 2021
• First Posted: February 23, 2021
• Study Start: May 16, 2022
• Primary Completion: December 15, 2022
• Study Completion: December 15, 2022
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)