Romosozumab in Women With Chronic SCI

Study Overview
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Brief Summary
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This two-year open-label pilot clinical trial will evaluate the efficacy and safety of romosozumab to treat bone loss in females with chronic spinal cord injury (SCI) and osteoporosis (OP). Participants will receive monthly injections of romosozumab during the first 12 months of the study. During the second year, participants will take oral alendronate tablets on a weekly basis.

Detailed Description
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This is a single-site, singe-arm, open-label pilot study to evaluate safety and efficacy of a sequential drug treatment (12 months of romosozumab injections followed by 12 months with alendronate tablets) to treat bone loss in women with chronic SCI and OP. During the first year, participants will receive monthly subcutaneous injections of romosozumab 210 mg. This drug works by increasing bone formation and is FDA-approved for treating OP in post-menopausal women at high risk of fracture or those who did not benefit from using other available OP treatments. During the second year, participants will take weekly oral alendronate 70 mg. Alendronate is FDA-approved for the treatment of osteopenia and the treatment of OP in post-menopausal women and men as well as for the prevention and treatment of glucocorticoid-induced OP. In this study, it will be used to help maintain any increases in bone mass gained from the year of treatment with romosozumab. Twelve participants will receive the study drug treatment, take daily supplements (calcium and vitamin D), and return to the research site for study visits over the course of two years. Computerized tomography (CT) imaging, dual-energy X-ray absorptiometry (DXA) imaging, and serum bone markers will be collected at baseline, 3 months, 6 months, 12 months, and 24 months.

Official Title
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Effects of Romosozumab on Bone Health in Women With Spinal Cord Injury and Osteoporosis

Conditions
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Osteoporosis, Bone Loss, Osteopenia, Osteoporosis, Spinal Cord Injuries, Chronic Spinal Paralysis

Intervention / Treatment
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* Drug: Romosozumab
* Drug: Alendronate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Female sex SCI 6 or more months prior to enrollment Non-ambulatory status (Walking Index for Spinal Cord Injury II score of 3 or less) Osteoporosis by DXA defined as a t-score of -2.5 at any skeletal site (lumbar spine, total hip, or femoral neck) or a t-score of -2.0 plus a history of a fragility fracture Good general health, as determined by the study investigator Able to understand and agree to informed consent in English Able and willing to complete all the study visits Females of childbearing potential must be willing and able to use an effective method of contraception or practice abstinence throughout the course of the study and up to 90 days after the last use of study drug. Vitamin D 25-hydroxy levels ≥ 20 ng/ml (subjects may be repleted and retested prior to baseline) Normal serum calcium levels (based on current local laboratory normal range) No known endocrinopathies (diabetes type 1 or 2, treated thyroid conditions can be included) Normal serum thyroid stimulating hormone and/or T4 levels (based on current local laboratory normal ranges) Able to take oral medication sitting upright for at least 30 minutes Exclusion criteria: Have Paget's disease of the bone Have abnormal laboratory values that in the judgement of the investigator would put the participant at increased risk of treatment Any active gastrointestinal condition that results in malabsorption Abnormalities of the esophagus which delay emptying such as stricture or achalasia Known hypersensitivity to romosozumab or alendronate Increased risk of aspiration Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (e.g., tooth extraction, dental implants, oral surgery in the past 6 months), poor oral hygiene, periodontal and/or pre-existing dental disease, or planned invasive dental procedure over the next two years Heterotopic ossification of the knee region that interferes with CT analysis History of bone metastasis and skeletal malignancies History of alcoholism or drug abuse within the 2 years prior to study screening, which in the opinion of the investigator may affect subject's health and/or study commitment Other medical conditions that in the opinion of the investigator would preclude the subject from completing the study Currently being prescribed anticonvulsants at a dose or frequency that is determined to interfere with bone metabolism as determined by the investigator Currently being prescribed glucocorticoids, other than inhaled glucocorticoids Current or use during past 5 years of any bone-active agents, including any FDA approved treatment (e.g., teriparatide, abaloparatide, denosumab, any bisphosphonate (oral or IV), raloxifene, bazedoxifene, hormone therapy (estrogen and estrogen/progestin) and calcitonin) as well as any strontium-containing compounds. Pregnant, planning to become pregnant, or lactating Any history of stroke or cardiovascular disease other than controlled hypertension Renal insufficiency (calculated creatinine clearance less than 35 ml/min) Any other neurological impairment that may impair ambulation or muscle function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Females with Chronic SCI<br>12-month treatment with monthly subcutaneous romosozumab injections (210 mg), followed by 12-month treatment with weekly oral alendronate tablets (70 mg) | Drug: Romosozumab<br>* Year 1 study drug<br>* Other names: Evenity;Drug: Alendronate<br>* Year 2 study drug<br>* Other names: Fosamax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in knee integral vBMC | Change from baseline to the Month 12 visit in integral volumetric bone mineral content (vBMC) at the distal femur as obtained via CT imaging of the index knee | Baseline - 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hip BMD | Change from baseline to the Month 12 visit in bone mineral density (BMD) at the total hip and femoral neck as obtained via DXA imaging of the index hip | Baseline - 12 months | 
| Change in hip vBMC | Change from baseline to the Month 12 visit in vBMC at the hip as obtained via CT imaging of the index hip | Baseline - 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Romosozumab, Alendronate, Spinal Cord Injury, Osteoporosis, Romosozumab (Evenity), Alendronate (Fosamax), Bone Diseases, Metabolic Bone Diseases, Anabolic Treatment, Bisphosphonate, Bone Density, Spinal Cord Diseases, Physiological Effects of Drugs