Investigation of the Simplify® Cervical Artificial Disc

Study Overview
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Brief Summary
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This study is intended to demonstrate that the Simplify® Disc is at least as safe and effective as conventional anterior cervical discectomy and fusion (ACDF) when used to treat one level between C3 to C7 for cervical degenerative disc disease (DDD) defined as intractable radiculopathy (arm pain and/or a neurological deficit) with or without neck pain or myelopathy due to a single-level abnormality localized to the level of the disc space in subjects who are unresponsive to conservative management.

Detailed Description
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The objective of this clinical study is to evaluate the safety and effectiveness of the Simplify® Disc for treatment of DDD compared to conventional ACDF for reconstruction of the disc space at one level between C3 to C7 for DDD defined as intractable radiculopathy (arm pain and/or a neurological deficit) with or without neck pain or myelopathy due to a single-level abnormality localized to the level of the disc space that is unresponsive to conservative management.

Official Title
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Clinical Study Protocol for the Investigation Of The Simplify® Cervical Artificial Disc

Conditions
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Cervical Degenerative Disc Disease

Intervention / Treatment
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* Device: Simplify Disc
* Device: Anterior Cervical Discectomy & Fusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be between 18 and 60 years of age; Have symptoms of cervical degenerative disc disease (DDD) at one cervical level from C3 to C7 defined as intractable radiculopathy (arm pain and /or a neurological deficit) with or without neck pain or myelopathy due to a single-level abnormality localized to the level of the disc space and radiographic evidence of at least one of the following; Spondylosis (defined by the presence of osteophytes or dark disc) on CT or MRI or; Disc height decreased by ≥ 1 mm when compared to adjacent levels on radiographic film, CT, or MRI or Disc herniation on CT or MRI; Have at least one of the following radiculopathy or myelopathy symptoms in neck and/or arm; Pain or paresthesias in a specific nerve root distribution from C3 to C7, Decreased muscle strength of at least one level on the 0-5 scale, or Abnormal sensation, including hyperesthesia or hypoesthesia. Have at least one of the following: At least six weeks of prior conservative treatment (e.g., physical therapy and/or use of anti-inflammatory medications and muscle relaxants at the manufacturer's recommended therapeutic dose); The presence of progressive symptoms (e.g., increasing numbness or tingling) or Signs of nerve root compression. Have a Neck Disability Index (NDI) greater than or equal to 40 on a scale of 100 (moderate disability); Be appropriate for treatment using an anterior surgical approach; Be likely to return for all follow-up visits and Be willing and able to provide Informed Consent for study participation. Exclusion Criteria: Marked cervical instability on resting lateral or flexion/ extension X-ray (translation > 3 mm or > 11 degrees rotation to that of either adjacent non-treatment level); Non discogenic neck pain or non discogenic source of symptoms (e.g., tumor, rotator cuff injury, etc.); Radiographic confirmation of severe facet disease or facet degeneration; Bridging osteophytes; Less than 2 degrees of motion at index level; Prior surgery at the level to be treated, except laminotomy without accompanying facetectomy; Prior fusion at any cervical level; More than one neck surgery via anterior approach; Previous trauma to the C3-C7 levels resulting in compression or bursting; Documented presence of a free nuclear fragment at cervical levels other than the study level; Axial neck pain only (no radicular or myelopathy symptoms); Symptomatic DDD at more than one cervical level; Severe myelopathy (less than 3/5 muscle strength); Any paralysis; Recent history (within previous six months) of chemical or alcohol dependence; Active systemic infection; Infection at the site of surgery; Prior disc space infection or osteomyelitis in the cervical spine; Any terminal, systemic or autoimmune disease; Metabolic bone disease (e.g., osteoporosis/osteopenia , gout, osteomalacia, Paget's disease); Any disease, condition or surgery which might impair healing, such as; Diabetes mellitus requiring daily insulin management, Active malignancy, History of metastatic malignancy. Current or extended use (> 6 months) of any drug known to interfere with bone or soft tissue healing; Known PEEK, ceramic, titanium allergy; Arachnoiditis; Significant cervical anatomical deformity at the index level or clinically compromised cervical vertebral bodies at the index level due to current or past trauma (e.g., by radiographic appearance of fracture callus, malunion, or nonunion) or disease (e.g., ankylosing spondylitis, rheumatoid arthritis); Currently experiencing an episode of major mental illness (psychosis, major affective disorder, or schizophrenia), or manifesting physical symptoms without a diagnosable medical condition to account for the symptoms, which may indicate symptoms of psychological rather than physical origin; Pregnancy at time of enrollment, or planning to become pregnant, since this would contraindicate surgery ; Use of spinal stimulator at any cervical level prior to surgery; Currently a prisoner; Currently involved in spinal litigation which may influence the subjects reporting of symptoms or Participation in any other investigational drug, biologic or medical device study within the last 30 days prior to study surgery.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Anterior cervical discectomy & fusion (ACDF)<br> | Device: Anterior Cervical Discectomy & Fusion<br>* This study will utilize a non-concurrent historical control with subject-level data on a parallel group design. The historical control group will be formed from the randomized ACDF arm (N=133) of the recently completed Kineflex®|C Disc trial.<br>* Other names: ACDF;|
| Experimental: Simplify Disc<br>Simplify Disc | Device: Simplify Disc<br>* Simplify Disc at one level in the cervical spine.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Composite Clinical Success (CCS) of Simplify Disc | Individual success for the Simplify® Disc subjects is defined as at least a 15 point improvement in Neck Disability Index (NDI) Score at 24 months compared with baseline, maintenance or improvement in neurologic status at 24 months compared with baseline, no device failures or revision, reoperation, removal and/or supplemental fixation within 24 months of index procedure; and the absence of major adverse events within 24 months. Individual success for the control ADCF device subjects is defined as at least a 15 point improvement in NDI Score at 24 months compared with baseline, maintenance or improvement in neurologic status at 24 months compared with baseline, no device failures or revision, reoperation, removal and/or supplemental fixation within 24 months; and the absence of major adverse events within 24 months. NDI scale is reported in a range from 0 - 100, with 0 consistent with best ability to function and 100 with worst ability to function. | Baseline, 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With 15-point Improvement in NDI at 3 Months (Time to Recovery) | Time to recovery is defined as time to first 15-point improvement in NDI NDI scale is reported in a range from 0 - 100, with 0 consistent with best ability to function and 100 with worst ability to function. | Baseline, 3 Months | 
| VAS Neck and Arm Pain | Changes of at least 20 mm on a 100mm will be regarded as clinically significant VAS 0mm (no pain); VAS 100mm (worst pain) | Baseline, 24 Months | 
| Neurological Status | Neurological success was defined as maintenance or improvement in neurologic status at Month 24 as compared to baseline, as determined by the independent Clinical Events Committee (CEC). The CEC reviews neurological exams of motor, sensory, reflex, clumsiness, atrophy, cramping, spasms, numbness, dysphagia, dysphonia, and myelopathic gait to make an adjudication determination. | Baseline, 24 Months | 
| SF-12 Physical Component Score (PCS) Maintenance or Improvement | The PCS is a sub-score of the SF-12. The SF-12 is a multipurpose short form survey with 12 questions all selected from the SF-36 Health Survey. The questions were combined, scored, and weighted to create two scores that provide glimpses into mental and physical functioning and overall health-related-quality of life. Higher scores indicate better outcomes. Scores range from 0-50. Data was not collected on SF-12 in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design. | Baseline, 24 Months | 
| SF-12 Mental Component Score (MCS) Maintenance or Improvement | The MCS is a sub-score of the SF-12. The SF-12 is a multipurpose short form survey with 12 questions all selected from the SF-36 Health Survey. The questions were combined, scored, and weighted to create two scores that provide glimpses into mental and physical functioning and overall health-related-quality of life. Higher scores indicate better outcomes. Scores range from 0-50. Data was not collected on SF-12 in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design. | Baseline, 24 Months | 
| Patient Questionnaires- Treatment Satisfaction Health Survey- | Question 1 - how does the subject rate satisfaction with the treated received was compared between groups at Month 24. Answer options ranged from very dissatisfied to very satisfied. | 24 Months | 
| Odom's Criteria Results | Results at 24 months for the investigational Simplify® Disc and at 24 months for the control ACDF will also be categorized by the physician according to Odom's Criteria. | 24 Months | 
| Dysphagia Handicap Index (DHI) | Dysphagia Handicap Index (DHI scale) for the investigational Simplify® Disc at 24 months compared to baseline. A higher score is indicative of a less desirable outcome. It is scored 0-100. Data was not collected on DHI in the historical ACDF control group. Only Simplify Disc subjects are reported. This was pre-specified in the study design. | Baseline, 24 Months | 
| Average Disc Height (Index Level) | Change in average disc height (index level) was compared to the baseline measurements and scored by an independent core lab (MMI). Average disc height is calculated as the simple average of the anterior and posterior disc heights. | Baseline, 24 Months | 
| Average Disc Height (Above the Index Level) | Change in average disc height (Above the index level) was compared to the baseline measurements and scored by an independent core lab (MMI). Average disc height is calculated as the simple average of the anterior and posterior disc heights. | Baseline, 24 Months | 
| Average Disc Height (Below the Index Level) | Change in average disc height (below the index level) was compared to the baseline measurements and scored by an independent core lab (MMI). Average disc height is calculated as the simple average of the anterior and posterior disc heights. | Baseline, 24 Months | 
| Superior Adjacent Level Disc Degeneration | Outcome reports the number and percentage of subjects with adjacent level disc degeneration (ALDD) above the index level. | Baseline, 24 Months | 
| Inferior Adjacent Level Disc Degeneration | Outcome reports the number and percentage of subjects with adjacent level disc degeneration (ALDD) below the index level. | Baseline, 24 Months | 
| Device Migration | Device migration assesses significant movement of the implant postoperatively | Baseline, 24 Months | 
| Facet Deterioration | Facet degeneration was assessed using MRI for the investigational Simplify Disc at 24 months compared to baseline. Facet degeneration was not assessed in the ACDF historical control group, as there is no 24 month MRI. This was pre-specified in the study design. | Baseline, 24 Months |