Use of Forteo (Teriparatide) in Posterolateral Lumbar Spine Fusion

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of 12 weeks of daily treatment with teriparatide on spine fusion in adult patients who are undergoing multi-level posterolateral spine fusion surgery for degenerative conditions of the lumbar spine.

Detailed Description
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For patients undergoing spine fusion surgery, non-fusion (or pseudarthrosis) is one of the major complications that can lead to poor clinical outcomes. Therefore, treatments that promote or augment fusion are highly desirable. Teriparatide (Forteo, recombinant human parathyroid hormone [1-34]) is a systemically administered peptide hormone that is FDA-approved for the treatment of osteoporosis in postmenopausal women or other populations at high risk for fracture. While teriparatide has been shown to enhance spinal fusion in several rodent and rabbit studies, no clinical studies to date have examined its effect on spinal fusion in humans. While Forteo is FDA approved, and IND is required for this trial to study an unapproved indication: Posterolateral Lumbar Spine Fusion. This single-site two-year prospective randomized double-blind placebo-controlled study is designed to examine the effects of peri-operative teriparatide treatment in older adults undergoing multi-level posterolateral lumbar spine fusion. All eligible patients seen at the UCSF Spine Center will be invited to enroll in the study. Upon enrollment, patients will have screening labs drawn in conjunction with their routine pre-operative work-up, to include complete blood count (CBC), chemistry panel including calcium level, liver function tests (LFTs) including alkaline phosphatase, parathyroid hormone (PTH) level, and 25-hydroxyvitamin D level. If eligible after screening labs are completed, they will be scheduled for bone density (DEXA) scan and be randomized in a 2:1 ratio to receive daily subcutaneous injections of teriparatide 20 ug/d or placebo. The total duration of treatment will be 12 weeks, with two weeks pre-operative and 10 weeks post-operative treatment. Patients will be scheduled to attend all standard post-operative follow-up clinic visits, which will be at 6 weeks, 3 months, 6 months, and 12 months after surgery. At 3 months post operative visit, patients will have lab drawn for calcium. At each follow-up visit, AP and lateral x-ray radiographs will be taken of the lumber spine to assess progression of bone healing and positioning of any hardware placed. Participants will be asked to complete a pain Visual Analog Score (VAS), European Quality of Life-5 Dimensions (EQ-5D), and Oswestry Disability Index (ODI) questionnaire at each visit for assessment of clinical outcomes. Thin-section helical CT scans of the lumbar spine will be taken at 12 months after surgery for definitive assessment of fusion. All radiographs will be evaluated by a blinded panel of three reviewers including a radiologist and a spine surgeon to assess primary outcome.

Official Title
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Assessment of the Efficacy of Forteo (Teriparatide) in Patients Undergoing Posterolateral Lumbar Spinal Fusion

Conditions
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Lumbar Spondylosis, Lumbar Spondylolisthesis, Adult Degenerative Lumbar Scoliosis

Intervention / Treatment
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* Biological: teriparatide
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 60-90 years with lumbar spondylosis, spondylolithesis, or adult degenerative scoliosis, including disc pathology, stenosis, deformity, instability, or postdecompression revision, who are scheduled to undergo three-level or greater posterolateral lumbar spinal fusion. Willing and able to use a pen-type delivery system to administer daily subcutaneous injections. Exclusion Criteria: Use of bone morphogenic protein (BMP) posterolaterally during the fusion procedure. Previous spinal fusion at the intended fusion levels. Prior use of Forteo (teriparatide). Use of digoxin. Paget's Disease of bone. History of primary skeletal malignancy, presence of bone metastases, or previous skeletal exposure to therapeutic irradiation. Elevated serum calcium, serum PTH >70 pg/ml, 25-hydroxyvitamin D <12 ng/mL, or active liver disease. History of symptomatic nephro- or urolithiasis in the past two years. History of malignant neoplasm in the past five years, except for superficial basal cell carcinoma or squamous cell carcinoma. Carcinoma in situ of the uterine cervix treated in the past year.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Forteo, Terapeptide 20 ug subcutaneous injection | Biological: teriparatide<br>* Teriparatide 20 ug subcutaneous injection daily for 12 weeks<br>* Other names: recombinant human parathyroid hormone (1-34);|
| Placebo Comparator: Control<br>Saline placebo | Biological: Placebo<br>* Saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Spine Fusion, Measured by the Number of Participants With Complete Spine Fusion at 1 Year | Quality of spine fusion, measured by the number of participants with complete spine fusion at 1 year. Spine fusion at one year was assessed using thin-section helical computed tomography (CT) scan of the lumbar spine. | One year | 
| Time to Spine Fusion |  | One year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Reported Outcomes Measured by: Visual Analog Score (VAS), European Quality of Life - 5 Dimensions (EQ-5D) and Oswestry Disability Index (ODI) Scores at 1 Year | The self-reported pain Visual Analog Score (VAS), the score range is 0-100 with higher scores indicating more pain. European Quality of Life - 5 Dimensions (EQ-5D) is a standardized instrument for measuring generic health status, the scale range is from 0.000 (death) to 1.000 (perfect health). Oswestry Disability Index (ODI) provides information about how back or leg pain is affecting the ability to manage in everyday life, the points range from 0-50, which is doubled and reported as a percentage. Higher scores indicate higher disability. | One year | 
| Adverse Effects | Number of participants with serious adverse events and other (not including serious) adverse events at one year are reported. | One year |