Romosozumab to Improve Bone Mineral Density and Architecture in Chronic SCI

• Status: Recruiting
• Trial end date: 2024-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Treatment for sublesional bone loss (osteoporosis) in persons with chronic, motor-complete spinal cord injury (SCI) has been limited and unsuccessful to date. Romosozumab, a sclerostin antagonist, has potential to increase bone formation (anabolic) and decrease bone resorption (anti-catabolic) in persons with chronic SCI. Conventional anti-resorptive therapy alone would not be anticipated to reverse sublesional bone loss in a timely manner because the skeleton below the level of lesion in chronic SCI is assumed to be in a low turnover state. However, because there is a high likelihood that the bone accrued while on romosozumab will be lost once discontinued, denosumab, an anti-resorptive agent, will be administered after treatment with romosozumab, to maintain or, possibly, to continue to increase, bone mineral density (BMD).

The purpose of this study is to address the gap in the treatment of osteoporosis in individuals with chronic SCI by partially restoring BMD with romosozumab treatment for 12 months and then to maintain, or further increase, BMD with denosumab treatment for 12 months. A two group, randomized, double-blind, placebo-controlled clinical trial will be conducted in 39 participants who have chronic (>3 years), motor-complete SCI and areal BMD (aBMD) values at the distal femur of at the distal femur 0.7 g/cm2 but 1.0 g/cm2 measured by dual photon X-ray absorptiometry (DXA). The intervention group will receive 12 months of romosozumab followed by 12 months of denosumab, and the control group will receive 12 months of placebo followed by 12 months denosumab.

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

Details

• Lead Sponsor: VA Office of Research and Development
• Collaborator: Kessler Institute for Rehabilitation
• Treatments: Denosumab

Criteria

Inclusion Criteria:

• Traumatic SCI [C4-T10 [upper motor lesions as determined by the International Standards for Neurological Classification for Spinal Cord Injury (ISNCSCI) impairment scale]; ISNCSCI score A & B

• Duration of injury 3 years

• Males and females (premenopausal) between the ages of 18 and 50 years old (the upper age limit is to reduce the influence of age on the ability of the skeleton to respond to pharmacologic stimulation)

• aBMD at the distal femur 0.7 g/cm2 but 1.0 g/cm2 (determined at screening)

Exclusion Criteria:

• Long-bone fracture of the leg within the past year

• History of prior bone disease (Paget's hyperparathyroidism, osteoporosis, etc.)

• Active and/or history of coronary heart disease or stroke within the past year

• Postmenopausal women

• Men with known hypogonadism prior to SCI

• Anabolic therapy longer than six months duration after SCI

• Glucocorticoid administration longer than three months duration within the last year, and/or 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

• Endocrinopathies (hyperthyroidism, Cushing's disease or syndrome, etc.)

• Severe underlying chronic disease (e.g., COPD, end-stage heart disease, chronic renal failure)

• Heterotopic ossification (HO) of the knee region (the distal femoral epiphysis is the primary endpoint); HO to any other boney region will not prevent study participation as long as contraindicated medications have not been prescribed)

• Chronic alcohol abuse

• Hypocalcemia

• Pregnancy

• Prescribed a bisphosphonate for HO, or prescribed any other agent to treat osteoporosis other than calcium and vitamin D

• Electrical stimulation of the lower extremities

• Current diagnosis of cancer or history of cancer

• Osteosarcoma

• Life expectancy less than 5 years