The Effects of 12-months of Denosumab on Bone Density in Prevalent Kidney Transplant Recipients

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a Phase 2 Multi-Center Clinical Trial (safety and effectiveness trial) in 60 patients (40 denosumab; 20 placebo) who have had a kidney transplant for 12-months or longer with more than 30% of kidney function. The investigators will test whether denosumab safely improves bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) and improves bone strength by high resolution peripheral quantitative computed tomography (HR-pQCT) in the subset of patients recruited at Columbia University Irving Medical Center. These data will inform the development and execution of a larger trial to test if denosumab prevents fractures in kidney transplant recipients.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Thomas Nickolas, MD MS
• Treatments: Denosumab

Criteria

Inclusion criteria

1. Men and women

2. All race-ethnicities

3. Age ≥ 18 years

4. ≥ 12-months after kidney transplantation (living or deceased donor recipient)

5. Stable allograft function over the previous year defined as:

1. No rejections

2. No more than a 15% decline in Glomerular filtration rate (GFR) over the prior year

6. Allograft GFR ≥ 30 mL/minute/1.73 m2 (MDRD or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) per local lab reporting)

7. 25OHD ≥ 30 ng/mL (determined at screening visit)

8. Serum calcium ≥ 9.0 mg/dL (determined at screening visit)

9. T-Score at the spine including and between -1.0 and -3.5 (determined at screening visit)

10. Must have had a routine dental exam within 6-months of study recruitment

11. Must agree to continue with routine dental exams over the course of the study

12. Has not undergone an invasive dental procedure (i.e., tooth extraction, dental implants, oral surgery) within ≤ 3-months of recruitment

13. Must agree to referral to metabolic bone disease specialist at the end of the study

14. Women of child bearing potential must be willing to use one form of effective contraception over the course of the study

Exclusion Criteria

1. Allograft GFR < 30 mL/minute/1.73 m2 (MDRD or CKD-EPI per local lab reporting)

2. Within 24-months of starting renal replacement therapy

3. Prevalent or occult vertebral fractures

4. History of post-transplantation non-basal cell carcinoma cancers

5. Non-ambulatory

6. Malignancy requiring chemotherapy or metastatic to bone

7. Non-transplant related metabolic bone diseases that alter bone mineral density, including but not limited to Primary hyperparathyroidism, Paget's, Osteogenesis Imperfecta

8. Within one-year of parathyroidectomy

9. Untreated hyperthyroidism for 6-months or longer

10. Untreated hypothyroidism for 6-months of longer

11. Medical diseases (end stage liver, lung or heart, intestinal malabsorption)

12. Use within the prior year of bisphosphonates, teriparatide, selective estrogen receptor modulators, testosterone, estrogen, denosumab, abaloparatide, calcitonin, and romosozumab

13. Allergy to components within the denosumab preparation or to denosumab

14. Weight > 300 pounds

15. Parathyroid hormone (PTH) > 450 pg /mL

16. Will undergo an invasive dental procedure (i.e., tooth extraction, dental implants, oral surgery) within the next 12-months

17. Pregnant

18. Planned pregnancy during the course of the study