A Pilot Proof of Concept Study with Paired-Design on the Effectiveness of Metal Related Artifact Reduction of Hip Arthroplasty Implants or Other Metallic Hardware Using Radiofrequency Pulse Polarization Optimization in 3T MRI
This is a single-center single-arm clinical trial with a paired design which compares the effectiveness of 3T MRI with (modified) and without (standard) radiofrequency pulse polarization optimization in reducing metal-related artifacts in patients with hip arthroplasty implants or other metallic hardware. Twenty participants with symptomatic primary total hip arthroplasty or other metallic hardware will be imaged with both methods. The results of the two methods will be compared in reference to the size of the artifact-degraded regions, visibility of the normal structures and the rate of abnormality detection.
A Pilot Randomized Trial of Post-Operative Biomarker-Guided Precision Medicine with Rivaroxaban and Atorvastatin for Cardiovascular Risk Reduction
The purpose of this randomized trial is to assess adherence to a low-dose direct oral anticoagulant and high-intensity statin versus usual care for 6 months in patients with post-operative abnormal troponin blood tests indicative of heart damage, termed “Myocardial Injury after Noncardiac Surgery” (MINS). The data obtained will be used to assess feasibility and optimize study design (entry criteria, study endpoints, sample size calculation, site selection) and recruitment strategies for the future randomized clinical trial studying biomarker-based care in post-operative patients at elevated CV risk.
A Pilot Study Examining Conscious Awareness and Cognitive Experiences During Deep Hypothermic Circulatory Arrest
This study aims to use methods developed in the AWARE II study (NYU IRB #17-00241) to diagnose awareness during Deep Hypothermic Circulatory Arrest (DHCA) procedures.Our overall hypothesis is that mental and cognitive activity as well as conscious awareness may occur during cardiac standstill states, including DHCA and that this may be related to underlying cortical activity. The purpose of this proposal is to refine study methods originally developed for use during CPR to measure cerebral oxygenation and function using cerebral oximetry and EEG, as well as tests of consciousness and awareness.
A Platform Study of RAS(ON) Inhibitor Combinations in Patients with RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)
This study is designed to test how effective a new drug called AZD0486 (BITE for CD19) is for patients relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) who have already tried at least 1-2 other treatments. This study has three parts: Part A will test increasing doses of AZD0486 to find a dose with few side effects; Part B will test up to two doses from Part A to decide the best dose to use in the next phase; and Part C will use the best dose from Part B to see how well it works in more patients. AZD0486 will be given as an IV infusion on certain days of each 28-day cycle, with close monitoring for side effects. Side effects and effectiveness will be checked regularly, and the study will continue until enough data is collected to understand how well AZD0486 works and how safe it is.
A prospective long-term confirmatory follow up trial in highly sensitized patients treated with imlifidase or standard of care in the ConfIdeS (20-HMedIdeS-17) trial
A controlled, randomized, efficacy Phase 3 trial (ConfIdeS, 20-MedIdeS-17) comparing imlifidase with standard of care (SoC) in enabling highly sensitized patients to kidney transplantation is performed by Hansa Biopharma to support an Accelerated Marketing Approval of imlifidase. The present trial is a confirmatory long-term follow-up of patients participating in the ConfIdeS trial intended to gather information on clinical endpoints representing a meaningful clinical benefit i.e., patient and graft survival, and graft function, on a long-term basis (2-5 years after randomization in the ConfIdeS trial), and to confirm the positive benefit-risk balance of imlifidase.
A prospective multicenter open-label randomized actively controlled parallel-group Phase 3 clinical trial to evaluate efficacy safety and tolerability of IMA203 versus investigator s choice of treatment in patients with previously treated unresectable or metastatic cutaneous melanoma (ACTengine IMA203-301)
This study is testing a new treatment, IMA203, for patients with advanced skin cancer (cutaneous melanoma) who have already received treatment before. It will compare IMA203 to standard treatments chosen by the doctor to see which works better and is safer. Patients will be randomly placed into one of two groups: one getting IMA203 with chemotherapy and immune-boosting medicine (IL-2), and the other getting a standard treatment. Patients must have a specific genetic marker (HLA-A*02:01) to join, which will be tested before the study. Doctors will check how long patients live without their cancer getting worse (PFS) and overall survival (OS). A safety board will monitor the study, and experts will review scan results to track cancer progression. Some patients may receive temporary treatments before starting the main study treatment. Patients will have regular check-ups, scans every 12 weeks, and quality-of-life assessments. They will stay in the study until their cancer worsens, they start another treatment, they choose to leave, or the study ends. After the study, those who received IMA203 may be asked to join a long-term follow-up study.
A Prospective Multicenter Randomized Two-Arm Single-blind Superiority Trial to Evaluate the Safety and Efficacy of the MagicTouch Sirolimus-Coated Balloon in the Treatment of Coronary Drug-Eluting Stent In-Stent Restenosis (MAGICAL ISR)
The treatment for narrowed or blocked arteries often involves stents, which are inserted into heart blood vessels to alleviate blockages. Drug-eluting stents (DES) release medication to prevent recurring blockages, known as restenosis. However, restenosis can still occur, sometimes necessitating further procedures. These may include placing additional stent layers or using balloon angioplasty (POBA) without new stents, though multiple layers can be a drawback. This study aims to compare the efficacy and safety of the MagicTouch™ Sirolimus-Coated Balloon combined with POBA versus POBA alone in patients with restenosis of prior DES. All participants will receive standard treatment for narrowed areas in previous DES with POBA. Some patients will also receive the MagicTouch™ balloon. The study will assess the effectiveness of adding this novel device to standard treatment.
A Prospective multicenter study to examine the influence of repairing the sub-scapularis on outcomes after reverse arthroplasty: A randomized controlled trial.
Determine how repairing the subscapularis vs. not repairing the subscapularis when subjects are implanted with the AltiVate Reverse® Shoulder System for reverse total shoulder arthroplasty affects isometric and isokinetic internal rotational strength.
A prospective randomized-controlled study to evaluate the effect of a standardized yoga practice on chronic back pain
Background:Chronic low back pain is notoriously difficult to treat and is a primary contributor to lost work days and excessive health expenditures, and whose treatment has, in part, contributed to the opioid crisis. Surgery is only an option in a minority of these patients, usually confined to those with structural instability. Yoga is an ancient modality whose benefits are currently being studied. There is enough data that the most recent ACP guidelines have included yoga as a treatment for chronic back pain, but more data needs to be generated regarding the efficacy of this modality in treating the chronic back pain population.Methods:We will perform a prospective, randomized trial with the hypothesis that yoga is superior (non-inferior) to usual care for chronic back pain. Inclusion criteria will be adult patients who have had chronic back pain (pain above the gluteal cleft of at least 3 months duration). Exclusion criteria will be patients who have an indication for surgery: fracture, infection, scoliosis, or spondylolisthesis. The study arm will involve a yoga protocol devised by Eddie Stern - a renowned Ashtanga yoga practitioner, and can include NSAIDs. The control arm will involve usual care - 6 weeks of physical therapy, NSAIDs, and epidural steroid injections. Outcome measures will be assessed by VAS, ODI, and SF-36 surveys to be given at 3 months, 6 months, 1 year, and 2 years.
A Prospective Randomized Double-Blind Sham-Controlled Multi-Center Pivotal Study to Evaluate the Efficacy and Safety of Duodenal Mucosal Resurfacing Using the Revita System in Subjects with Type 2 Diabetes on Insulin therapy
The Revita® System is an endoscopic treatment consisting of a single catheter and console designed to lift the duodenal mucosa with saline followed by controlled circumferential hydrothermal ablation of the mucosa.The exclusion of the duodenum from the passage of nutrients by surgical diversion appears to result in weight-independent improvements in glycemia associated with a reduction in insulin resistance. This effect is also notable in being almost immediate in its onset (within days) and durable over time (years). The gastrointestinal tract is now recognized to be the largest endocrine organ in the body. It releases gastrointestinal hormones in a finely tuned pattern to help the body achieve glucose homeostasis in the fasting and post-prandial states, with the gastro-intestinal mucosa playing the role as a critical sensing and secreting interface. Bypass of the proximal small bowel appears to modify the secretion of certain key gastrointestinal hormones that in turn lead to improvements in glucose homeostasis. This occurs without calorie malabsorption. Rather, these changes restore the ability of the liver to suppress endogenous glucose production in response to insulin, a physiologic process that is otherwise impaired in diabetes.There are two main theories on how the bypass of the proximal small bowel exerts such a strong anti-diabetic effect, both of which may explain the role of the small bowel in glucose homeostasis.29 First, some believe that the delivery of excess nutrients to the distal small bowel leads to enhanced secretion of GLP-1 (and perhaps additional related insulin-secreting hormones) from the GLP-1-rich entero-endocrine cells of the terminal ileum. Enhanced GLP-1 release into the bloodstream after an ingested meal has a number of beneficial effects on glucose homeostasis30.A second theory is that individuals with Type 2 Diabetes acquire mucosal alterations in their proximal small bowel that contribute to insulin resistance and glucose intolerance and that bypass of this segment is beneficial. Data from rats and humans suggest that prolonged exposure to a Western diet leads to an increase in enteroendocrine cell numbers and a subsequent gastric inhibitory peptide (GIP) after a meal.Other studies have demonstrated hypertrophy of the mucosa of the small bowel in subjects with diabetes.In this way, the insulin resistance of the body may arise from hormones produced by the proximal small bowel as a consequence of these mucosal alterations. The hypothesis is that bypass of the duodenum by nutrients prevents the release of these hormones and therefore immediately leads to an improvement in glucose tolerance after surgery.Moreover, it is now becoming increasingly recognized that the upstream surgical perturbation of the gastrointestinal tract, resulting in the exclusion of the duodenum, does indeed manifest a compelling anti-diabetic effect but the diabetes state of the patient is also a key determinant of outcome. Studies have now reported that the potency of the anti-diabetic effect manifested with metabolic surgery is contingent on or influenced by innate endogenous beta-cell reserve or insulin secretory capacity. In other words, surgery elicits powerful anti-diabetic effects but more notably in the presence of sufficient endogenous beta-cell secretory capacity. This raises important questions concerning a more targeted use of such interventions in individuals that have certain beta-cell reserve characteristics and/or certain companion pharmacological agents that augment beta-cell secretory function (e.g. GLP-1-receptor agonists) to best optimize outcome.A model of type 2 diabetes pathogenesis emerges from these observations. Namely, a life of excess fat and sugar ingestion in genetically prone individuals can lead to changes in the mucosa of the proximal small bowel. These mucosal changes, in turn, are associated with alterations in signals emanating from the proximal gut (including hormone secretion). This altered proximal gut signal exerts an effect that worsens insulin resistance, could negatively affect insulin secretion and may well drive the pathogenesis of T2D. In this context, duodenal exclusion through surgery or a medical device may reduce the abnormal signal emanating from the proximal gut, and thus improves glucose homeostasis.Duodenal mucosal resurfacing (DMR), using the Revita® System, is designed to mimic the metabolic benefit of the duodenal exclusion component of bariatric surgery, thereby eliciting an insulin-sensitizing effect. Duodenal Mucosal Resurfacing (DMR) consists of a highly controlled mucosal lift and ablation procedure of the post papillary duodenum using the Revita® System over the guided wire placed using a standard endoscope.The Revita® clinical data indicates that DMR exerts insulin-sensitizing like effects as evidenced by a lowering of HOMA-IR40, by an insulin-sensitizing metabolic signature by metabolomics testing (e.g., lowering of a-hydroxybutyrate, diacylglycerol, and peroxidase activity), and by other related insulin-sensitizing biomarker effects (including lowered hepatic transaminases and urinary microalbumin).Unlike bariatric surgery, which involves an anatomical bypass of the duodenum and therefore no exposure of ingested nutrients to the surface of that portion of the GI tract, DMR is designed to ablate and re-epithelialize the duodenal mucosal surface, thus allowing nutrients to be exposed to a newly regrown and normalized local mucosa. This infers that the duodenal mucosa surface is in some way abnormal in insulin resistant T2D subjects and is, therefore, emanating a potential ‘insulin resisting’ effect. This notion is supported by multiple lines of evidence: the duodenum undergoes a maladaptive hypertrophic response when exposed to unhealthy nutrients (i.e., fat, simple sugars); this change appears to be associated with an augmented insulin-resistant signal emanating from this portion of the bowel.This signal appears to be persistent and reversible in T2D, as revealed in post-bariatric surgery: in those individuals in whom metabolic improvement has been established after surgery, the acute re-exposure of the bypassed duodenum to nutrients quickly restores the insulin resistant, hyperglycemic, dysmetabolic condition that had existed pre-surgery ; and ablation technology applied to other tissue surfaces has shown that the natural tissue response to ablation is re-growth of a healthy tissue surface.Taken together, there is a strong rationale that the duodenal mucosa of T2D subjects is abnormal and that subjects would likely reap a metabolic benefit if the local duodenal mucosa is resurfaced through an ablation technique.In addition to the glycemic benefits previously seen, data has also indicated liver benefits after ablating abnormal duodenal mucosa in T2D. The C-20000 study, which did not require a NAFLD diagnosis at baseline, showed that approximately 85% of patients had fatty liver even in the presence of normal liver transaminases, confirming prior evidence of the growing epidemiologic overlap with T2D.Patients with NAFLD (liver MRI-PDFF > 5%)at baseline showed a large magnitude and a clinically meaningful reduction in liver fat content at week 12, confirming earlier findings of reductions in ALT through 2 years. These data provide insight into a potential therapeutic opportunity for DMR to favorably impact both T2D and NAFLD/NASH in a manner that can modify the natural history of these chronic and progressive diseases.