Secondary Prevention of Small Subcortical Strokes (SPS3): To define effective therapies for prevention of recurrent stroke and cognitive decline in patients with symptomatic small subcortical stroke or subcortical TIA. This study is looking at combined antiplatelet therapy and aggressive blood pressure lowering vs usual blood pressure management.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of SCH 530348 in Addition to Standard of Care in Subjects With a History of Atherosclerotic Disease: Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P – TIMI 50): To study to effects of SCH 530348 when administered orally in addition to the standard of care for a minimum of 1 year in subjects with documented atherosclerotic disease in patients with recently diagnosed coronary artery disease as manifested by an MI, ischemic (presumed thrombotic) cerebrovascular disease, or peripheral arterial disease.

Siblings with Ischemic Stroke Study (SWISS): To perform a multi-center study of sibling pairs with stroke to systematically screen for regions of the human genome that contain genes which increase the risk of having an ischemic stroke.

MRI and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE): Successful conduct of the trial will evaluate whether use of MRI is a rational and appropriate selection criterion for mechanical recanalization therapy for acute ischemic stroke. A positive trial will suggest substantial clinical benefit from embolectomy therapy in the group of patients with a penumbral MRI pattern, and permit informed design of definitive phase 3 trial(s) of endovascular embolectomy.

1.  Inhibition of Lipid Peroxidation and Cerebral Vasospasm by an Acetaminophen-Based Regimen in Patients with Aneurysmal Subarachnoid Hemorrhage-this is a single-center, double-blinded NIH funded clinical trial that we are conducting with Dr. John Oates in Clinical Pharmacology.

2.  SENTIS-Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke-this is a prospective, controlled, randomized, single-blind, multi-center study comparing NeuroFlo treatment plus standard medical management versus standard medical management alone in ischemic stroke less than 14 hours from symptom onset. The sponsor is CoAxia, Inc.

Dr. Moses

1. A four-arm randomized, double-blind, placebo-controlled, multicentre Phase II study to evaluate the safety, tolerability and efficacy as assessed by frequent MRI measures of three doses of atacicept monotherapy in subjects with relapsing multiple sclerosis (RMS) over a 36 weeks treatment course.  (Protocol 28063)

2.   A Phase 3 Randomized, Rater- and Dose-Blinded Study Comparing Two Annual Cycles of Intravenous Low- and High-Dose Alemtuzumab to Three-Times Weekly Subcutaneous Interferon Beta-1a (Rebif) in Patients with Relapsing-Remitting Multiple Sclerosis Who Have Relapsed On Therapy

3. Cerebrospinal Fluid Analysis Utilizing Recent Advances in Proteomic Research

4.  A Randomized, Multicenter, Placebo-Controlled and Active Reference (Glatiramer Acetate) Comparison Study to Evaluate the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis

5.Teva Pharmaceutical Industries, Ltd Protocol GA 9016 (FORTE): A Multinational, Multicenter, Randomized, Parallel-Group, Double-Blind Study, to Compare the Efficacy, Tolerability and Safety of Glatiramer Acetate Injection 40 mg/ml to that of Glatiramer Acetate Injection 20 mg/ml Administered Once Daily by Subcutaneous Injection in Subjects with Relapsing Remitting (R-R) Multiple Sclerosis (MS).

6. A 24-month double-blind, randomized, multicenter, placebo-controlled, parallel-group study comparing the efficacy and safety of 0.5 mg and 1.25 mg fingolimod (FTY720) administered orally once daily versus placebo in patients with relapsing-remitting multiple sclerosis

7. PHASE II, MULTICENTER,  RANDOMIZED, PARALLEL-GROUP, PARTIALLY BLINDED, PLACEBO AND AVONEX CONTROLLED DOSE FINDING STUDY TO EVALUATE THE EFFICACY, AS MEASURED BY BRAIN MRI LESIONS, AND SAFETY OF 2 DOSE REGIMENS OF OCRELIZUMAB IN PATIENTS WITH RRMS

8. A Phase II, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Safety, Tolerability and Efficacy Study of Add-on Cladribine Tablet Therapy with Rebif New Formulation in Multiple Sclerosis Subjects with Active Disease" (Serono, Inc.)

9.  Multi-center, Open-Label Study to Evaluate the Effects of Natalizumab Treatment on Fatigue and Cognition in Subject with
Relapsing Forms of MS 

10. Tysabri global observational program in safety

Dr. Sriram

1. A multi-center double-blind parallel-group placebo-controlled study of
 the efficacy and safety of   teriflunomide in patients with relapsing multiple
 sclerosis

2. A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients with Relapsing Remitting Multiple Sclerosis (CombiRx-Phase III) Extension study.

3. A Multi-Center, Double-Blind, Randomized Study Comparing the Combined Use of Interferon Beta-1a and Glatiramer Acetate to Either Agent Alone in Patients with Relapsing Remitting Multiple Sclerosis (CombiRx-Phase III).   

4. Extension Study to Biomarkers in Multiple Sclerosis  National Institute of Neurological Disorders and Stroke Biomarkers in Multiple Sclerosis Study
     
5.The Open-Label, Compassionate, Pilot use of Antibiotics for Patients with Progressive MS

6. Longitudinal analysis of immunoglobulin changes in the CSF of patients who present with clinically isolated syndrome or Relapsing Remitting Multiple Sclerosis

7. Regulation of p53 signaling defects in MS

8. Regulation of p53 by B-Interferon

9. Cerebrospinal fluid analysis utilizing recent advances in proteomic research

10. Regulation of expression and function of p53 by beta interferon

Title:  Innovative Tools for In vivo Computational Prediction of Pre-and Post-Operative Lumbar Stresses
Principle Investigator:  Joseph S. Cheng, M.D., M.S.
NIH Grant

Low back pain is the most common spine related problem, and treating it has become a rapidly growing segment of medicine.  New medical and surgical treatments, such as disc or facet joint replacement, may provide better alternatives to our current standard of care.  However, we need more biomechanical research to develop the appropriate tools to diagnose, help guide treatment, and assess the outcomes of these various treatments.  In conjunction with the University of Tennessee, we at Vanderbilt are developing predictive biomechanical models that allow us to do this.

In biomechanics, stress is a function of an applied force over an area of tissue.  It is assumed that pain is when this loading exceeds the capacity of the tissue to carry it, and is then associated with an injury to that regions tissue.  In other engineering fields, computational models are developed to determine failure modes in mechanical systems.  Although the human body differs in many ways from other systems, it can be modeled using modified tools and then analyzed to determine the kinetics (study of forces and loads) that may be associated with a patient’s symptom.  In our study, a mathematical model of the lumbar spine is being developed for diagnosis and treatment determination for low back pain (LBP). The overall goal is to determine whether contact stresses in the discs and joints can be predicted and ultimately reduced so that we can better understand progression of diseases such as arthritis.  Such degenerative diseases are associated with posture and loading, and we can design better implants with patient-specific models for improved pain reduction, longer wear ability, and potential reduction for revision or retrieval surgeries.  The models we propose to develop could eventually be used to predict in vivo contact stresses at the bearing surface interface (disc and facets) of the vertebral bodies of the lower back and assess surgical outcomes in terms of reduction of pain after fusion or disc replacement surgery. This could lead to better forms of treatment and better outcomes for our patients.

Title:  In Vivo Determination of 3D Kinematics for Subjects Having a Prestige Single Level Cervical Disk Replacement
Principle Investigator:  Joseph S. Cheng, M.D., M.S.

The cervical spine is a complex structure providing support and stability to the head while allowing complex physiological motions.  Patients with cervical spondylosis may require surgical treatment, with anterior cervical decompression and fusion (ACDF) surgery being one of the gold standard surgical techniques with successful long-term outcomes.  This has driven the explosion of this technique in surgical practice; however ACDF’s have been reported to significantly reduce the motion with pathological degeneration at adjacent levels described as adjacent segment degeneration and disease.  Biomechanical studies have shown that a loss of motion at the ACDF level created greater segment motions and increased load or intradiscal pressure at its adjacent levels, which is believed to have induced subsequent degeneration at those levels. This has promulgated the development of motion sparing devices such as cervical arthroplasty or dynamic stabilization devices that preserve motion of the region.  However, the need for these devices remains controversial as some studies have demonstrated that there is no obvious evidence for the development of adjacent segment degeneration after ACDF.  Part of the disagreement for the need of cervical arthroplasty resides with the lack of clinical tools to assess cervical kinematics and kinetics in the every day clinical practice.  There are laboratory tools to assess the three-dimensional (3D) kinetics and kinematics, such as telemetric implants or mathematical models, but these remain cumbersome and difficult to implement in the outpatient clinic setting.  Our proposal is to develop a method of assessing biomechanical normalization in the cervical spine in the outpatient setting for application in determining a patients need for surgery, which type of surgery, and measure the outcomes of either surgical or non-surgical treatments.

Title:  Comparing surgical to conservative management in the treatment of Type II odontoid fractures among the elderly
Principle Investigator:  Joseph S. Cheng, M.D., M.S.
Co-Investigator:  Kurt Eichholz, M.D.
Sponsor:  AOSpine North America

Management of odontoid fractures among those ≥ 65 years of age remains controversial.
Type II odontoid fractures attract the most controversy with respect to appropriate management due to their poor healing rates. While external bracing (i.e., conservative) techniques have traditionally been employed with varying success, surgical intervention has become more popular as a primary treatment option, often preserving motion through the atlanto-axial complex, especially with anterior screw fixation. Rates of nonunion among conservatively managed patients have ranged from 4% to 64%.  Though nonunion rates appear higher among patients treated conservatively, it is unclear if this is associated with poorer function or quality of life relative to those treated with surgery. There is a paucity of literature on this topic and those studies that have been done are of poor quality. The purpose of this study is to compare the safety and effectiveness of surgical versus conservative management of type II odontoid fractures among patients ≥ 65 years of age. Of secondary interest is to determine if there are differences in outcomes between anterior screw fixation and posterior fusion of these fractures.

Title:  Stabilimax NZ™ Dynamic Spine Stabilization System
Principle Investigator:  Joseph S. Cheng, M.D., M.S.
Co-Investigator:  Kurt Eichholz, M.D.
Sponsor:  Applied Spine Technologies, Inc.

The Applied Spine Technologies, Stabilimax NZ study offers an alternative to a traditional posterior lumbar spinal fusion for patients with moderate to severe spinal stenosis.  This study will assess whether the investigational device Stabilimax NZ, which is for investigational use only, is at least as safe and effective as the control therapy of fusion in patients receiving decompression surgery for the treatment of clinically symptomatic spinal stenosis at one or two contiguous vertebral levels from L1-S1.  This study is available to patients ages 21 and over who meet the inclusion and exclusion criteria for the study.  More information regarding this study can be found at http://legandbackpainstudy.com/ or http://stabilimaxstudy.com/.

Main Study Title:  A Multi-Center Observational Study of Patients Undergoing Minimally Invasive TLIF Surgical Approach Compared to Open TLIF ApproachUsing TheVIPERPedicle Screw System
Sub Study Title:  Examination of the Difference in Muscle Disruption in Minimally-Invasive vs. Open Lumbar Fusion Using MRI Imaging and Creatine Phosphokinase Levels)
Principle Investigator:  Kurt Eichholz, M.D.
Co-Investigator:  Joseph S. Cheng, M.D., M.S.
Sponsor:  DePuy Spine

Main Study: Lumbar fusion surgery is performed using several surgical approaches. Transforaminal Lumbar Interbody Fusion (TLIF) has shown to be a technically feasible method that allows for neural decompression and interbody bone grafting.  This clinical study is being conducted to evaluate patient outcomes following a 1 or 2-level lumbar fusion using a minimally invasive TLIF surgical approach with posterior fixation for degenerative disc disease (DDD) or degenerative Spondylolisthesis (not more than Grade I) compared to a similar cohort of patients who undergo an open TLIF surgical approach with posterior fixation.

Sub Study: In recent years, many advances have been made in minimally-invasive approaches to the lumbar spine. These approaches typically involve a paramedian, muscle-splitting approach, as opposed to the traditional midline subperiosteal muscle dissection.  Several studies have shown that minimally invasive approaches decrease narcotic requirement, hospital length of stay, and allow for faster mobilization.  In addition, other studies have shown the deleterious effects of midline lumbar subperiosteal dissection, in terms of muscle strength and laboratory values (CPK).  However, there have been no randomized studies in the literature that have directly compared or quantified the difference in muscle disruption between open and minimally invasive approaches. This study will be of value, in that by using a randomized study design and a uniform group of patients, and by utilizing the same instrumentation in all patients, the difference in muscle disruption will be quantified on imaging, including MRI, and laboratory value in a prospective, randomized fashion.

A DOUBLE-BLIND, RANDOMIZED, MULTICENTER EFFICACY AND SAFETY STUDY OF PREGABALIN (LYRICA) AS MONOTHERAPY IN PATIENTS WITH PARTIAL SEIZURES

A Historical-controlled, Multicenter, Double-blind, Randomized Trial to Assess the Efficacy and Safety of Conversion to Lacosamide 400mg/day Monotherapy in Subjects with Partial-onset Seizures

A Phase 3, Randomized, Double-Blind, Parallel, Placebo-Controlled, Multicenter Study, with Optional Open-Label Continuation, of the Efficacy and Safety of Vanquix™ Auto-Injector (Diazepam Injection) for the Management of Selected, Refractory, Patients with Epilepsy who Require Intermittent Medical Intervention to Control Episodes of Acute Repetitive Seizures

For questions / concerns contact: epilepsy.research@vanderbilt.edu