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Active, Not Recruiting

NCT Number: NCT04232657

Romosozumab to Improve Bone Mineral Density and Architecture in Chronic SCI

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 or incomplete SCI and areal BMD (aBMD) values at the distal femur of at the distal femur <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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Spinal Cord Injury (=3 Years) Central Nervous System Diseases Nervous System Diseases Spinal Cord Diseases Spinal Cord Injuries Sublesional Bone Loss Secondary to SCI Trauma, Nervous System Wounds and Injuries

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Kessler Institute for Rehabilitation, West Orange, New Jersey, United States

Loading trial locations.

About this study

Persons with chronic spinal cord injury (SCI) have markedly reduced bone mass and the loss of skeletal architectural integrity, which predisposes them to low-impact fractures. Currently, there is no practical treatment to reverse the severe bone loss in persons with chronic SCI. In the proposed study, a dual pharmacological intervention will be tested to improve bone health. Restoration of bone mass below the level of injury would be expected to reduce the morbidity associated with fractures and permit safer participation in upright activities. Quality of life would be substantially improved because of the ability to engage more securely in activities of daily living and to integrate into the community. Despite the depressed skeletal activity below the level of lesion in persons with chronic SCI, net bone loss occurs because resorption exceeds formation, with a difference between these rates in those with SCI being greater than that observed in the able-bodied population. Thus, it would be anticipated to be of value in persons with chronic SCI to increase bone turnover with the objective to increase bone formation over that of bone resorption. In a preclinical study that administered an anti-sclerostin antibody to rats 12 weeks after complete spinal cord transection bone, mineral density (BMD) was almost fully restored at the distal femoral metaphysis, with improved bone structure, and mechanical strength; in contrast, vehicle-treated animals after complete spinal transection had a marked reduction in distal femoral metaphysis BMD and a deterioration in bone structure and mechanical strength. When used to treat postmenopausal osteoporosis, romosozumab, a human monoclonal anti-sclerostin antibody, was more effective to increase bone mineral density (BMD) and to reduce fracture than any other anti-resorptive or bone-anabolic agent, and this effect was also evident for the appendicular skeleton, which is the site in individuals with chronic SCI of greatest bone loss and most frequent fracture. Because of the absence of clinical options available for the treatment of osteoporosis in individuals with chronic paralysis, the investigators have proposed to test an antagonist of sclerostin, which is a potent bone anabolic agent with proven efficacy in treating women with postmenopausal osteoporosis, to improve bone mass and reduce fragility fractures.

Thirty-nine male and female subjects with chronic, motor-complete or incomplete SCI (>3 years post injury, American Spinal Injury Association Impairment Scale A & B) between the ages of 18 and 55 years old (for females) or 65 years old (for males) who have aBMD at the distal femur at the distal femur <1.0 g/cm2 will be recruited for participation in a randomized, double-blind, placebo-controlled, parallel group clinical trial. The outcome measures of the proposed study are bone mineral density (BMD) by peripheral quantitative computed tomography (pQCT) and dual energy x-ray absorptiometry (DXA), and biochemical markers of bone resorption and formation. This prospective, randomized, placebo controlled clinical trial will take place at the James J. Peters VA Medical Center (JJPVAMC) and Kessler Institute for Rehabilitation (KIR) (each facility will perform patient enrollment and study procedures).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Motor-complete or incomplete SCI [all levels of lesion] classified using International Standards for Neurological Classification for Spinal Cord Injury (ISNCSCI) impairment scale] as ISNCSCI score A-C
  • Duration of injury >3 years
  • Males (18-65 years old) and females (premenopausal, between the ages of 18 and 55 years old).
  • aBMD at the distal femur <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, 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

Treatment and study plan

Romosozumab

Drug

39 subjects with chronic SCI will be studied with a 2:1 ratio of randomization of drug to placebo. Romosozumab (210mg SQ) will be administered once a month for 12 months. Participants will arrive at the JJPVAMC or KIR once a month to receive injections of romosozumab or placebo. A designated unblinded healthcare professional will be responsible for administering these injections.

Other names: Evenity

Denosumab

Drug

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. Denosumab will be administered to both groups (treatment and placebo) for an additional 12 months. Participants will be asked to arrive at the JJPVAMC once every 6 months to receive injections of denosumab by a healthcare professional.

Other names: Prolia

Placebo

Drug

Thirteen (13) of the thirty-nine (39) subjects enrolled in this study will be randomly selected to receive placebo (NS SQ) injections for 12 months (baseline - month 11). The placebo injections will be administered by an unblinded healthcare professional (registered nurse / physician). Participants will be blinded to their group assignment (romosozumab treatment or placebo).

Other names: Normal Saline (NS) injection

Primary outcomes

  1. Change in vBMD at the Distal Femur, measured by pQCT after 12 months of romosozumab treatment

    Time frame: Baseline (0), Month 6, Month 12

    Percent change of volumetric BMD (vBMD) (mg/cm^3)at the distal femur, measured by peripheral quantitative computed tomography (pQCT) (slice thickness 2.4mm, default voxel size of 0.5mm), with 12 months of romosozumab therapy. vBMD measurements will be taken at baseline, month 6 and month 12.

  2. Change in vBMD at the distal femur after an additional 12 months of denosumab treatment

    Time frame: Month 18, Month 24

    Percent change of Integral vBMD (mg/cm^3)at the distal femur, measured by pQCT (slice thickness 2.4mm, default voxel size of 0.5mm), after additional 12 months of denosumab therapy. vBMD measurements will be taken by pQCT at months 18 and 24.

Other outcomes

  1. Additional variables by pQCT - vBMD Proximal Tibia

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Percent change in proximal tibia vBMD (mg/cm^3), measured by pQCT (slice thickness 2.4mm, default voxel size of 0.5mm) at baseline, month 6, month 12, month 18, and month 24.

  2. Additional variables by pQCT - tBMD Distal Femur

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Percent change in distal femur trabecular BMD (tBMD) (mg/cm^3) will be measured by pQCT (slice thickness 2.4mm, default voxel size of 0.5mm) at baseline, month 6, month 12, month 18, and month 24.

  3. Additional variables by pQCT - tBMD Proximal Tibia

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Percent change in proximal tibia tBMD (mg/cm^3) will be measured by pQCT (slice thickness 2.4mm, default voxel size of 0.5mm) at baseline, month 6, month 12, month 18, and month 24.

  4. Additional variables by pQCT - cortical BMD of the tibia (38% of the tibial length)

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Percent change in cortical vBMD (mg/cm^3) will be measured by pQCT (slice thickness 2.4mm, default voxel size of 0.5mm) at baseline, month 6, month 12, month 18, and month 24.

  5. Additional variables by pQCT - Distal Tibia Microarchitecture

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Through the use of a custom software package (pQCT OsteoQ, Inglis Software Solutions Inc., Hamilton, ON) combined threshold-based and region-growing algorithms will be used to measure trabecular microarchitecture [trabecular separation (Tb.Sp), bone volume fraction (BV/TV), trabecular number (Tb.N), and trabecular thickness (Tb.Th)] at baseline, month 6, month 12, month 18, and month 24.

  6. Additional variables by DXA - aBMD Distal Femur and Proximal Tibia (i.e. knee)

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Percent change of regional BMD of the knee (e.g., distal femoral and proximal tibial epiphyses using the orthopedic knee software commercially available from GE Lunar). The starting point to acquire the knee is set on the tibia approximately 10 cm distal from the edge of the patella, with the scan field extending to the epiphysis and metaphysis of the distal femur. aBMD measurements will be taken at Baseline (0), Month 6, Month 12, Month 18, Month 24.

  7. Additional variables by DXA - aBMD Hip

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Percent change in aBMD of the hips (total dual dip and subregions) will be measured at Baseline (0), Month 6, Month 12, Month 18, Month 24. Accepted values for T-score and Z-scores of the hip will be utilized.

  8. Biomarkers for Bone Resorption (CTx)

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    Change in levels of the circulating biochemical markers of bone resorption and formation before (baseline) and after initiating romosozumab therapy (1, 3, 6, and 12 months), and then after 6 and 12 months of denosumab administration will be measured. Levels of serum C-telopeptide (CTx) (ABclonal. 86 Cummings Park, Woburn, MA) will be measured as the biomarker of bone resorption.

  9. Biomarkers for Bone Formation (osteocalcin, alkaline phosphatase, P1NP)

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    Change in levels of the circulating biochemical markers of bone resorption and formation before (baseline) and after initiating romosozumab therapy (1, 3, 6, and 12 months), and then after 6 and 12 months of denosumab administration will be measured. Serum osteocalcin (Alpco Diagnostics, Salem, NH), bone alkaline phosphatase (MyBiosource, Inc., San Diego, CA) and propeptide of type 1 procollagen (P1NP) (MyBiosource, Inc., San Diego, CA) will be measured as biomarkers of bone formation.

  10. Calcium Metabolism Studies

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    Serum total and ionized calcium concentration, 24-hour urine calcium, 25 OH-vitamin D level (DiaSorin Inc. Stillwater, MN), 1,25 (OH)2-vitamin D level (Quest Diagnostics), and intact PTH level (ALPCO Diagnostics, Salem, NH) will be measured.The serum 25 OH-vitamin D level will be measured at baseline and 12 and 24 months; more frequent measurement will be performed, if indicated. Serum total and ionized calcium concentrations will be measured at baseline, 1, 3 months, and at 6-month intervals until month 24.

  11. General Endocrine Studies

    Time frame: Baseline (0), Month 12, Month 24

    Serum thyroid function (T3, T4, & TSH; DiaSorin Inc. Stillwater, MN) will be determined by kit assay.

  12. Additional variables by pQCT - Distal Tibia Microarchitecture

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Through the use of a custom software package (pQCT OsteoQ, Inglis Software Solutions Inc., Hamilton, ON) combined threshold-based and region-growing algorithms will be used to bone volume fraction (BV/TV)at baseline, month 6, month 12, month 18, and month 24.

  13. Additional variables by pQCT - Distal Tibia Microarchitecture

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Through the use of a custom software package (pQCT OsteoQ, Inglis Software Solutions Inc., Hamilton, ON) combined threshold-based and region-growing algorithms will be used to measure trabecular number (Tb.N) at baseline, month 6, month 12, month 18, and month 24.

  14. Additional variables by pQCT - Distal Tibia Microarchitecture

    Time frame: Baseline (0), Month 6, Month 12, Month 18, Month 24

    Through the use of a custom software package (pQCT OsteoQ, Inglis Software Solutions Inc., Hamilton, ON) combined threshold-based and region-growing algorithms will be used to measure trabecular thickness (Tb.Th)at baseline, month 6, month 12, month 18, and month 24.

  15. Calcium Metabolism Studies

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    Serum ionized calcium concentration will be measured at baseline, months 1, 3, 6, 12, 18, and 24.

  16. Calcium Metabolism Studies

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    24-hour urine calcium will be measured at baseline, months 1, 3, 6, 12, 18, and 24.

  17. Calcium Metabolism Studies

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    25 OH-vitamin D levels (DiaSorin Inc. Stillwater, MN) will be measured at baseline and 12 and 24 months; more frequent measurement will be performed, if indicated.

  18. Calcium Metabolism Studies

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    1,25 (OH)2-vitamin D level (Quest Diagnostics), will be measured at baseline and 12 and 24 months; more frequent measurement will be performed, if indicated.

  19. Calcium Metabolism Studies

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    Intact PTH level (ALPCO Diagnostics, Salem, NH) will be measured at Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

  20. General Endocrine Studies

    Time frame: Baseline (0), Month 12, Month 24

    Serum cortisol will be measured by kit assay (MP Biomedicals, Orangeburg, NY).

  21. General Endocrine Studies

    Time frame: Baseline (0), Month 12, Month 24

    Serum total testosterone (T) will be determined by kit assay (MP Biomedicals, Orangeburg, NY).

  22. General Endocrine Studies

    Time frame: Baseline (0), Month 12, Month 24

    Serum free testosterone (calculated from total T, albumin and SHBG) will be measured by kit assay (MP Biomedicals, Orangeburg, NY).

  23. General Endocrine Studies

    Time frame: Baseline (0), Month 12, Month 24

    Serum estradiol (E2) will be measured by kit assay (MP Biomedicals, Orangeburg, NY).

  24. General Endocrine Studies

    Time frame: Baseline (0), Month 12, Month 24

    Serum growth hormone (GH) will be measured by kit assay (MP Biomedicals, Orangeburg, NY).

  25. General Endocrine Studies

    Time frame: Baseline (0), Month 12, Month 24

    Serum insulin-like growth factor-1 (IGF-I) will be measured by kit assay (ALPCO Diagnostics, Salem, NH).

  26. Biomarkers for Bone Formation

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    Change in levels of bone alkaline phosphatase (MyBiosource, Inc., San Diego, CA) at baseline, month 1, month 3, month 6, month 12, month 18, and month 24.

  27. Biomarkers for Bone Formation

    Time frame: Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24

    Change in levels of propeptide of type 1 procollagen (P1NP) (MyBiosource, Inc., San Diego, CA) at baseline, month 1, month 3, month 6, month 12, month 18, and month 24.

Sponsors and collaborators

Lead sponsor

VA Office of Research and Development

Fed

Collaborators

  • Kessler Institute for Rehabilitation

Registry information

Acronym: Chronic Romo

Important dates

Study start
2021
Primary completion
2026
Study completion
2027
First posted
Jan 18, 2020
Registry last updated
Apr 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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