Spinal Cord Injury (=3 Years) Clinical Trial
— Chronic RomoOfficial title:
Romosozumab to Improve Bone Mineral Density and Architecture in Chronic SCI
| Verified date | May 2024 |
| Source | VA Office of Research and Development |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 36 |
| Est. completion date | March 1, 2027 |
| Est. primary completion date | February 5, 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 65 Years |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | James J. Peters VA Medical Center, Bronx, NY | Bronx | New York |
| United States | Kessler Institute for Rehabilitation | West Orange | New Jersey |
| Lead Sponsor | Collaborator |
|---|---|
| VA Office of Research and Development | Kessler Institute for Rehabilitation |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Additional variables by pQCT - vBMD Proximal Tibia | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Additional variables by pQCT - tBMD Distal Femur | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Additional variables by pQCT - tBMD Proximal Tibia | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Additional variables by pQCT - cortical BMD of the tibia (38% of the tibial length) | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Additional variables by pQCT - Distal Tibia Microarchitecture | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Additional variables by DXA - aBMD Distal Femur and Proximal Tibia (i.e. knee) | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Additional variables by DXA - aBMD Hip | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Biomarkers for Bone Resorption (CTx) | 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. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | Biomarkers for Bone Formation (osteocalcin, alkaline phosphatase, P1NP) | 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. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | Calcium Metabolism Studies | 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. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | General Endocrine Studies | Serum thyroid function (T3, T4, & TSH; DiaSorin Inc. Stillwater, MN) will be determined by kit assay. | Baseline (0), Month 12, Month 24 | |
| Other | Additional variables by pQCT - Distal Tibia Microarchitecture | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Additional variables by pQCT - Distal Tibia Microarchitecture | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Additional variables by pQCT - Distal Tibia Microarchitecture | 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. | Baseline (0), Month 6, Month 12, Month 18, Month 24 | |
| Other | Calcium Metabolism Studies | Serum ionized calcium concentration will be measured at baseline, months 1, 3, 6, 12, 18, and 24. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | Calcium Metabolism Studies | 24-hour urine calcium will be measured at baseline, months 1, 3, 6, 12, 18, and 24. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | Calcium Metabolism Studies | 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. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | Calcium Metabolism Studies | 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. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | Calcium Metabolism Studies | 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 | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | General Endocrine Studies | Serum cortisol will be measured by kit assay (MP Biomedicals, Orangeburg, NY). | Baseline (0), Month 12, Month 24 | |
| Other | General Endocrine Studies | Serum total testosterone (T) will be determined by kit assay (MP Biomedicals, Orangeburg, NY). | Baseline (0), Month 12, Month 24 | |
| Other | General Endocrine Studies | Serum free testosterone (calculated from total T, albumin and SHBG) will be measured by kit assay (MP Biomedicals, Orangeburg, NY). | Baseline (0), Month 12, Month 24 | |
| Other | General Endocrine Studies | Serum estradiol (E2) will be measured by kit assay (MP Biomedicals, Orangeburg, NY). | Baseline (0), Month 12, Month 24 | |
| Other | General Endocrine Studies | Serum growth hormone (GH) will be measured by kit assay (MP Biomedicals, Orangeburg, NY). | Baseline (0), Month 12, Month 24 | |
| Other | General Endocrine Studies | Serum insulin-like growth factor-1 (IGF-I) will be measured by kit assay (ALPCO Diagnostics, Salem, NH). | Baseline (0), Month 12, Month 24 | |
| Other | Biomarkers for Bone Formation | 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. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Other | Biomarkers for Bone Formation | 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. | Baseline (0), Month 1, Month 3, Month 6, Month 12, Month 18, Month 24 | |
| Primary | Change in vBMD at the Distal Femur, measured by pQCT after 12 months of romosozumab treatment | 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. | Baseline (0), Month 6, Month 12 | |
| Primary | Change in vBMD at the distal femur after an additional 12 months of denosumab treatment | 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. | Month 18, Month 24 |