Denosumab (DMAB) Discontinuation And Switching In Glucocorticoid-Induced Osteoporosis (GIOP): A Pilot Study

• Status: Recruiting
• Trial end date: 2024-08-31
• Target enrollment: 0
• Participant gender: All

Summary

Investigators will test the hypothesis that an increase in bone turnover markers (e.g. carboxy-terminal collagen crosslinks (CTX) and P1NP) in patients currently taking chronic glucocorticoids will be attenuated more in those who switch from denosumab to "late" zoledronic acid (9 months after last denosumab dose) compared to participants randomized to "early" zoledronic acid (6 months after last denosumab dose) or weekly alendronate (6 months after last denosumab dose).

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alabama at Birmingham
• Collaborators: Maastricht University; Vrije Universiteit Brussel
• Treatments: Alendronate; Denosumab; Glucocorticoids; Zoledronic Acid

Criteria

Inclusion Criteria:

• Women and men, age 18 years or older and able to provide informed consent (IC)

• ≥ 3 months of glucocorticoid use at > 7.5 mg /day (prednisone equivalent dose) and anticipated to remain on glucocorticoids for at least six months

• A baseline BMD T-score of ≤ -2.0 at the lumbar spine, total hip, or femoral neck; OR

• A BMD T-score ≤ -1.0 at the lumbar spine, total hip, or femoral neck and a history of an osteoporotic fracture.

Exclusion Criteria:

• • Patients with fewer than three lumbar vertebrae that could be evaluated on dual energy x-ray absorptiometry (DXA)

• Treatment with bisphosphonates in the preceding 2 years

• Greater than 24 months (>4 injections) of prior treatment with denosumab

• Women of childbearing potential, who are not currently using birth control, are pregnant, planning to become pregnant, or are breastfeeding. For women of childbearing potential: refusal to use 2 highly effective forms of contraception and to continue this practice for 7 months after last injection of study medication*

• Men planning to conceive in the next 12 months

• Unstable systemic medical condition

• Uncontrolled hyperthyroidism

• Uncontrolled hypothyroidism

• History of Addison disease

• History of osteomalacia

• History of osteonecrosis of the jaw (ONJ)

• History of atypical femur fracture

• History of tooth extraction, jaw surgery, dental implants, or other dental surgery within the prior 6 months

• History of anorexia nervosa, bulimia (by history or physical) or obvious malnutrition.

• Invasive dental work(implants/surgery) planned in the next 2 years

• History of Paget's disease of bone

• Other bone diseases which affect bone metabolism

• Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)]

• Hypercalcemia >10% above upper limit of normal (ULN)

• Elevated transaminases or total bilirubin ≥ 2.0 x ULN

• History of any solid organ or bone marrow transplant

• Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma or localized squamous cell carcinoma of the skin)

• Hypocalcemia <10% below lower limit of normal (LLN)

• Estimated glomerular filtration rate < 30 mL/minute/1.73 m^2

• Intolerance to calcium supplements, vitamin D supplements

• Contraindication to, or poorly tolerant of denosumab therapy (including hypersensitivity to the drug)

• Contraindication to, or poorly tolerant of zoledronic therapy (including hypersensitivity to the drug)

• Contraindication to, or poorly tolerant of alendronate (including hypersensitivity to the drug and sever gastro-intestinal intolerance to oral bisphosphonates)

• Recipient of an investigational drug within 4 weeks prior to study drug administration

• Not a good candidate for study participation in opinion of investigator