Clinical trial NCT05101018: Treatment With Romosozumab Versus Denosumab to Improve Bone Mineral Density and Architecture in Subacute SCI
Official title: Treatment With Romosozumab Versus Denosumab to Improve Bone Mineral Density and Architecture in Subacute SCI
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Osteoporosis
Spinal Cord Injuries
Keywords: Osteoporosis
Spinal Cord Injuries
Dual Energy X-ray Absorptiometry
Denosumab
Romosozumab
Lead sponsor: James J. Peters Veterans Affairs Medical Center
Sponsor class: FED
Collaborators: name: Kessler Institute for Rehabilitation
First posted: 2021-10-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1: romosozumab administered monthly from baseline to month 11 followed by denosumab at month 12 and 18.

Arm 2: denosumab administered at baseline, month 6, 12, and 18
Primary purpose: PREVENTION

Brief summary: The objective of the proposed work is to determine whether administration for 12 months of romosozumab followed by 12 months of denosumab will maintain bone mass at the knee in subjects with subacute SCI compared to 24 months of denosumab administration alone.


Eligibility criteria: Inclusion Criteria:

1. Traumatic motor-complete or incomplete SCI C4-L2 (AIS grade A-C);
2. Duration of SCI less than 6 months;
3. Males and females (premenopausal) between the ages of 18 and 55 years old; and a safe range of BMD right above the knee as determined by study staff review;

Exclusion Criteria:

1. Active and/or history of coronary heart disease or stroke;
2. Bone cancer;
3. Long-bone fracture of the leg within the past year;
4. History of prior bone disease (for example, Paget's hyperparathyroidism, osteoporosis, etc.);
5. Postmenopausal women;
6. Men with known low functioning tests before SCI;
7. Drugs geared toward increasing BMD longer than a six month duration after SCI;
8. As determined by study staff review of my medication history of glucocorticoid administration longer than three months duration within the last year
9. Abnormalities of my endocrine glands such as hyperthyroidism, Cushing's disease or syndrome, etc.;
10. Severe underlying chronic disease (for example chronic obstructive pulmonary disease (COPD), end-stage heart disease, chronic renal failure);
11. Heterotopic ossification (HO) of the distal femur (the knee end of the thigh bone). HO is a condition where bone tissue forms outside of the skeleton. If HO is found in any other area than the distal femur it will not prevent my participation in the study.;
12. History of chronic alcohol abuse;
13. Diagnosis of hypercalcemia (high levels of calcium in the blood);
14. Pregnancy;
15. As determined by study staff review of my medications a bisphosphonate for heterotopic ossification (HO), or other medications to treat osteoporosis other than calcium and vitamin D;
16. Current diagnosis of cancer or history of cancer;
17. As determined by study staff review of my medications, prescribed moderate or high dose corticosteroids (\>40 mg/d prednisone or an equivalent dose of other corticosteroid medication) for longer than one week, not including drug administered to preserve neurological function at the time of acute SCI; and
18. Life expectancy less than 5 years.

Primary outcomes:
measure: Bone mineral density (BMD) of the distal femur metaphysis
timeFrame: Baseline to 24 months
Secondary outcomes:
Other outcomes:
Locations:
city: West Orange
country: United States
facility: Kessler Institute for Rehabilitation
state: New Jersey
city: Bronx
country: United States
facility: James J. Peters VA Medical Center
state: New York
Study officials:
affiliation: Kessler Institute for Rehabilitation
name: Steven C Kirshblum, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lewiecki EM, Dinavahi RV, Lazaretti-Castro M, Ebeling PR, Adachi JD, Miyauchi A, Gielen E, Milmont CE, Libanati C, Grauer A. One Year of Romosozumab Followed by Two Years of Denosumab Maintains Fracture Risk Reductions: Results of the FRAME Extension Study. J Bone Miner Res. 2019 Mar;34(3):419-428. doi: 10.1002/jbmr.3622. Epub 2018 Dec 3.
citation: Cosman F, Crittenden DB, Ferrari S, Khan A, Lane NE, Lippuner K, Matsumoto T, Milmont CE, Libanati C, Grauer A. FRAME Study: The Foundation Effect of Building Bone With 1 Year of Romosozumab Leads to Continued Lower Fracture Risk After Transition to Denosumab. J Bone Miner Res. 2018 Jul;33(7):1219-1226. doi: 10.1002/jbmr.3427. Epub 2018 May 17.
citation: McClung MR, Brown JP, Diez-Perez A, Resch H, Caminis J, Meisner P, Bolognese MA, Goemaere S, Bone HG, Zanchetta JR, Maddox J, Bray S, Grauer A. Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized, Double-Blind, Phase 2, Parallel Group Study. J Bone Miner Res. 2018 Aug;33(8):1397-1406. doi: 10.1002/jbmr.3452. Epub 2018 May 22.