Clinical trials

Stiff Person Syndrome (SPS) is a rare autoimmune disorder, characterized by: a) incapacitating diffuse muscle stiffness prominent in the axial, abdominal and thoracolumbar paraspinal muscles leading to hyperlordosis, difficulty turning and bending; b) painful muscle spasms precipitated by external stimuli with difficulty performing routine daily activities; and c) slow freezing gait with frequent falls and need for walking aids leading to disability. SPS is due to impaired inhibitory GABAergic neurotransmission associated with high-titer IgG antibodies against Glutamic Acid Decarboxylase (GAD), the rate-limiting enzyme for the synthesis of the inhibitory gammaaminobutyric acid (GABA). Although SPS patients respond to IVIg based on the PI's controlled study (NEJM 2001), several patients do not improve, or their response is modest and declines over time, as documented in a longitudinal study of 36 patients followed in our Jefferson clinic; because another controlled study we performed with Rituximab was negative and SPS is a progressive disease, new therapies are needed. Efgartigimod is an FcRn inhibitor that enhances the catabolism of circulating IgG; its subcutaneous, self-administered form, HYTRULO, has been effective and FDA-approved in patients with myasthenia gravis or CIDP poorly responding to IVIg. There is evidence that patients with myasthenia who also had SPS, Hytrulo not only helped their myasthenia but the SPS also impressively improved. The present study is an investigator- initiated, double-blind, placebo controlled, cross-over, trial in 26 GAD-positive SPS patients poorly responding to available therapies. Patients will be recruited from the large number of patients seen and referred to the PI who is known for his work in SPS and has conducted the 2 previous controlled trials. Although Hytrulo is approved as selfadministered subcutaneous drug with pre-refilled syringes, in this study will be given by a contracted home infusion company once a week to ensure convenience, safety and validity. Patients will be randomized by the Jefferson Pharmacy to receiving Hytrulo or identical hyaluronidase-containing placebo for 3 months; then they will be crossed-over to placebo/Hytrulo for another 3 months. Efficacy will be based on one primary endpoint, the stiffness index, previously validated by the PI, and on two also validated secondary endpoints of time to walk and excitability index. This design provides the statistical power to objectively assess a 25-50% or greater change and objectively determine if Hytrulo offers meaningful benefits in reducing stiffness and spasms, improving gait and increasing quality of life in SPS patients poorly responding to current therapies.

The goal of this clinical trial is to learn whether changing the diet can help improve gut health and support recovery from immune-related side effects caused by immune checkpoint inhibitor (ICI) cancer treatment in adults with solid tumors who develop moderate to severe immune-related side effects that require steroid treatment. The main questions it aims to answer are: Does a high-fermented food diet or a high-fiber resistant starch supplement change the gut microbiome (the bacteria and other microorganisms that live in the digestive tract) during treatment? Does either dietary approach improve gut microbiome diversity and function by the end of the 7-week intervention period? Researchers will compare participants assigned to a high-fermented food diet with participants assigned to high-fiber resistant starch supplementation to see if one approach leads to greater improvements in the gut microbiome and related biological measures. Participants will: Be randomly assigned to 1 of 2 dietary intervention groups: High-fermented food diet High-fiber resistant starch supplement Follow their assigned diet for 7 weeks, starting when their ICI treatment is restarted. Provide stool samples before the intervention begins and regularly throughout the study. Have blood samples collected at the start of the study and approximately every 3 to 4 weeks during participation. Provide skin and mouth swab samples at the beginning of the study and again at Week 7. Complete food diaries and symptom assessments during the study. Participate in a 2-week follow-up period after completing the dietary intervention. Researchers will also evaluate the safety of the dietary interventions, whether immune-related side effects return, how the immune system responds, and how closely participants follow their assigned diet.

This is an open-label, non-randomized trial that will be conducted at three clinical sites, Thomas Jefferson University (TJU), the Hospital of the University of Pennsylvania (HUP) and University of Bern (UB). Enrollment will be allocated into one of 4 different cohorts depending on the inclusion criteria for each cohort. Cohort 1: Patients scheduled for hepatic vein pressure gradient (HVPG) measurements will subsequently undergo two consecutive SHAPE (subharmonic aided pressure estimation) procedures using different ultrasound contrast agents (Definity \[Lantheus Medical Imaging, N Bilerica, MA, USA\] and Sonazoid \[GE Healthcare, Oslo, Norway\] in randomized order) to estimate portal pressures with a Logiq E10 scanner (GE Healthcare, Waukesha, WI, USA) and determine the reproducibility of the SHAPE algorithm. Cohort 2: Patients identified as having clinically significant portal hypertension (CSPH) will be monitored by SHAPE with Sonazoid for the duration of this project (18-24 months on average). These subjects will have follow-up ultrasound scans every 6 ± 2 months to check for hepatocellular carcinoma (HCC) (using the Barcelona-Liver Cancer staging system) as well as ascites and at those times a repeat SHAPE examination will be performed. Liver stiffness values will be measured with elastography as well. This cohort will examine if serial SHAPE can accurately predict development of ascites and other liver related events in patients with compensated cirrhosis undergoing routine HCC surveillance in a multi-center setting. Cohort 3: Subjects newly diagnosed with portal hypertension and starting treatment with non-selective β-blockers will be monitored with SHAPE and results compared to elastography measurements of liver stiffness with standard assessments (e.g., serum liver function tests and measurement of spleen size as well as platelet count). This cohort will establish if SHAPE can be used to monitor treatment response in patients identified with portal hypertension. Cohort 4: Patients with compensated advanced chronic liver disease scheduled for an endoscopy examination for screening of varices relative to the Baveno VI and the expanded-Baveno VI criteria as well as the AST to Platelet Ratio Index will undergo a SHAPE examination. This cohort will compare the predictive ability of SHAPE for allocating patients with compensated advanced chronic liver disease to screening of varices compared to the current standard of care.

The goal of the clinical trial is to evaluate the preliminary effectiveness and the implementation feasibility of the Targeted EHR-based Communication about Uncertainty (TECU) strategy in improving the quality of care transitions from the emergency department (ED) to home. The overall specific aims related to the trial are to test the preliminary effectiveness of TECU compared to standard of care in reducing patient uncertainty and return ED visits and evaluate the adoption of TECU, exploring patient and clinician barriers and facilitators to TECU implementation.

To date, there has been no head to head comparison of Upper Airway Stimulation (UAS) and Continuous Positive Airway Pressure (CPAP) utilizing a full night polysomnographic evaluation. With this study we aim to evaluate a pilot cohort of patients with OSA treated with CPAP or UAS using the WatchPAT polysomnography system.

The goal of this clinical trial is to learn how well contrast-enhanced ultrasound (CEUS) can diagnose ovarian cancer in patients with indeterminate or suspicious ovarian/adnexal lesions identified on routine ultrasound or MRI. The main questions it aims to answer are: How accurately can qualitative CEUS imaging features distinguish malignant from benign ovarian/adnexal lesions? How consistent are the CEUS assessments among different readers, and can combining CEUS findings with MRI and clinical information improve diagnostic performance? Participants will: Undergo a baseline pelvic ultrasound followed by CEUS imaging using an intravenous ultrasound contrast agent. Receive a second contrast injection during the same examination so that additional CEUS images can be obtained. Be followed for up to 1 year, with standard-of-care imaging or pathology used as the reference for determining whether the ovarian/adnexal lesion is benign or malignant.

Patients with an infected knee replacement will receive their standard of care surgical treatment of the infection, with and without additional ultrasound microbubble treatment (randomly divided 50/50 in the active and control groups). Subjects in the active group will receive a local bolus injection of antibiotics and ultrasound-active microbubbles within 24 hours of their revision surgery. The fundamental hypothesis is that a decrease in re-infection rates of at least 24% can be achieved in the active group relative to controls.

The goal of this observational study is to develop new ways to detect early changes associated with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. The study will examine whether changes in breathing, magnetic resonance imaging (MRI) of the brainstem and spinal cord, and blood markers can identify early signs of ALS before major physical changes occur. The main questions the study aims to answer are: * Can changes in automatic breathing help identify early ALS-related changes? * Can breathing measures distinguish people with ALS from people without ALS? * Do people with genetic risk for ALS who show changes in breathing also have changes in the brainstem and spinal cord or higher levels of blood markers associated with nerve damage? Participants will complete breathing and muscle function tests, an MRI scan of the brainstem and spinal cord, and blood testing. The study will include people with ALS, people with genetic risk for ALS who do not yet have symptoms, and healthy adults for comparison.

This phase II trial studies whether time restricted eating (TRE) works to improve outcomes in patients with stage I-III breast cancer receiving chemotherapy before surgery (neoadjuvant) with a body mass index (BMI) 25-40. TRE has been shown to elicit similar metabolic changes as calorie restriction such as reduction in blood glucose levels, improved insulin sensitivity, and reduction of tumor cell growth. TRE may improve outcomes in patients with breast cancer.

This phase III trial compares the use of contrast-enhanced multiparametric ultrasound (mp-US) to multiparametric magnetic resonance imaging (mp-MRI) for the diagnosis of clinically significant prostate cancer (PCa). A mp-US is a procedure in which a probe that sends out high-energy sound waves is inserted into the rectum. The sound waves are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissue called a sonogram. Perflutren lipid michrosphere (Definity) is a contrast agent that uses microbubbles to enhance ultrasound images of the prostate. Doctors hope to learn if the Definity-enhanced mp-US imaging technique can accurately direct targeted biopsy for the detection of clinically significant prostate cancer when compared to standard of care mp-MRI.

The objective of the pilot RCT is to evaluate the feasibility and acceptability of a Tai Chi intervention "TaiChi4Joint" vs. an HE AC group for relieving AIIA in women with hormone receptor positive stage I-III BCa. The investigators will pilot test our data collection for mechanism measures via three innovatively integrated biobehavioral pathways.

This is a phase 2a, open label, single arm, multi-site study of xaluritamig in mCRPC patients following treatment with ≥1 ARPI, taxane chemotherapy (if eligible) and stable or partial PSA response following 2 cycles of lutetium 177 vipivotide tetraxetan. Participants will continue treatment until clinical or radiographic progression of disease, withdrawal, or toxicity requiring discontinuation of therapy. All participants will be evaluated for overall response per RECIST v1.1,8 radiographic progression free survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) criteria, and PSA response. Approximately 30 participants will be enrolled. There is no data on response with alternative treatments following lutetium 177 vipivotide tetraxetan against which to benchmark the response rate. This phase 2a study will serve as an exploratory pilot to determine if a larger phase 2b study is warranted in this setting.

Phase I: Validating self-collection kit by comparing their results with clinical Pap smear results in a cohort of 20 patients. Phase II: Evaluate the feasibility and acceptability of the CHW4CervicalHealth: Use of a self-collection kit to improve cervical health screening intervention aimed to promote HPV self-collection uptake among screening-eligible and under-screened ethnic minority women in the community.

This study is a multicenter, open label phase I/ II trial to assess the safety and clinical efficacy of tebentafusp-tebn in combination with liver-directed therapies in HLA-A\*0201 positive patients with metastatic uveal melanoma. In Part 1 of the study, the Prinicipal Investigator will investigate the safety and efficacy of tebentafusp-tebn in combination with hepatic IE in patients with a low to moderate hepatic disease burden. In Part 2, the study will investigate the efficacy of tebentafusp-tebn in combination with TACE in patients with bulky hepatic disease.

This is a prospective, single arm, phase II clinical trial of neoadjuvant Tebentafusp (KIMMTRAK®) in patients with locally advanced primary uveal melanoma. Patients must be HLA-A\*02:01 with large, surgically unresectable (other than complete enucleation of the eye) primary uveal melanoma. The efficacy of this treatment will be assessed with the Simon's two stage design. The choice of design is guided by a desire to stop the trial early if the actual regression rate of primary uveal melanoma is 1% or lower.

This prospective clinical study will examine the ability of contrast-enhanced ultrasound (CEUS) to assess the treatment response of hepatocellular carcinoma (HCC) to transarterial radioembolization (TARE). HCC is the third leading cause of cancer mortality worldwide and the single fastest growing cause of cancer mortality in the United States. TARE is recommended for 15-25% of HCC patients. Treatment response is generally evaluated using contrast-enhanced CT or MRI 1-2 months and 4-6 months post-TARE. Although TARE is an effective therapy, assessment of treatment response using CT/MRI is challenging because CT/MRI frequently diagnoses tumor response as equivocal or non-progressing for up to 6 months post-TARE based on LI-RADS criteria. This delay in diagnosing tumor viability subsequently delays needed retreatment and can even serve as a barrier to transplantation. Our prior work in HCC locoregional therapy has shown CEUS provides improved sensitivity in detecting viable tumor following transarterial chemoembolization relative to traditional CT/MRI. Therefore, the investigators propose to evaluate both qualitative and quantitative CEUS as a tool for evaluating HCC post-TARE at similar time points of clinically recommended cross-sectional imaging, while also investigating the role of Kupffer phase imaging. The investigators plan to enroll a total of 30 patients scheduled for TARE of a treatment naïve HCC over an 18-month period, allowing for a minimum of 6 months follow up. Patients will undergo a CEUS examination within two weeks of their first two clinically indicated CT/MRI exams (obtained at Jefferson 1-2 months and 4-6 months post TARE). In patients retreated prior to their 4-6 month MRI, CEUS may also be performed in the absence of the MRI at this time point but prior to retreatment. Patients will be recruited across six major hospitals within the Jefferson Health Enterprise. Those eligible for participation will be identified by project co-investigators and contacted by the study coordinator to discuss participation and to explain the study. The patient will be given time to consider the risks and benefits of the study and ask questions about participation. If agreeable, the patient will then arrange with the project coordinator to come to Jefferson's center city campus to sign consent and take part in the research study.

The goal of this clinical trial is to determine whether cervical cerclage reduces the risk of preterm birth in patients with a short transvaginal ultrasound (TVU) cervical length (CL) ≤25mm between 24 0/7-26 6/7 weeks.

Einstein Medical Center in Philadelphia serves a diverse group of the patient population. The majority of patients have a diverse cultural background, low literacy, and poor social-economic status. Medication adherence for chronic medical problems is in a range of 40-70%. Medication adherence among patients on oral anti-cancer therapy is not studied in detail. The main objective is to study medication adherence to oral anticancer agents in patients with low literacy and poor socio-economic status.

The goal of this clinical trial is to learn if high-dose radiotherapy can provide sustained disease relief in moderate to severe, treatment resistant Hidradenitis suppurativa patients; could include any of the following: any sex/gender, and those greater then 18 years old. The main question\[s\] it aims to answer are: Outcome measure 1: Will radiotherapy change the number of inflammatory nodules, abscesses, and draining sinus tracts in the treated axilla compared with the untreated axilla? Outcome measure 2: Will radiotherapy positively change a patient's quality of life, pain levels and symptom burden? Participants will receive radiotherapy to one axilla affected by hidradenitis suppurativa. The contralateral axilla will not receive radiotherapy and will continue receiving the standard treatment regimen. Participants will... * Attend a baseline dermatology skin evaluation, complete multiple surveys and an optional participation in a biopsy * Attend multiple radiation sessions over 5 weeks * Attend 2 follow up visits with dermatology for skin evaluation, complete follow up surveys, and an optional biopsy.

This trial evaluates whether a network of peer genetic coaches is useful for addressing disparities in genetic testing and screening among African American men with prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). While genetic testing has become central to prostate cancer care, African American men are less likely seek testing due to lack of awareness, cultural beliefs, financial limitations, fear of discrimination, and mistrust in the healthcare system. A network of peer genetic coaches may help address barriers, beliefs, and needs of African American men in the community and provide navigation to increase engagement in genetic testing.

Given the lack of large multicenter datasets in the context of Spinal arteriovenous fistula, the strength of the evidence surrounding this rare disease is limited. SPIDER hence aims to address that by compiling patient-level data from centers all around the world.

This is an open-label, non-randomized, single-center, dose-escalation Phase 1 trial using a heterologous prime-boost strategy of vaccination with Ad5.F35-hGUCY2C-PADRE and recombinant Listeria monocytogenes (Lm-GUCY2C) vaccines in patients with advanced solid tumors including colorectal cancer, and small bowel adenocarcarcinomas who have progressed on available standard therapies. The study treatment will begin with Ad5.F35-hGUCY2C-PADRE vaccine administered intramuscularly (IM) once at the recommended Phase 2 dose (RPTD) dose, followed four weeks later by two administrations of Lm-GUCY2C intravenously (IV) at one of three escalating dose levels, four weeks apart. Treatment-related toxicity and development of immune responses will be evaluated every four weeks through week 8 after initial Lm-GUCY2C vaccination. Primary endpoints will include maximum tolerated dose (MTD) and safety and tolerability as measured by treatment emergent adverse events (TEAEs) and clinically significant changes in safety laboratory tests in the dose limiting toxicity (DLT) evaluation period defined as 4 weeks after the initial Lm-GUCY2C vaccination.

The proposed project seeks to evaluate the effectiveness and implementation of the Breastfeeding Education Support Tool for Baby (BEST4Baby) intervention, an mHealth-supported community-based peer counselor breastfeeding intervention for mothers in India. Given that rates of optimal infant feeding practices have remained stagnant over the past two decades in India, and that India is the most populous country and icontributes one-fifth of all global live births, this project could have major global health implications if the intervention is found to improve maternal breastfeeding practices and infant clinical outcomes. The project will also provide evidence needed to adopt BEST4Baby nationally and in other low resource communities.

A common complication following lung resection surgery is the presence of a post-operative air leak. This occurs when the resected lung tissue does not seal adequately, resulting in continued leakage of air from the lung. For most patient, an air leak will self-resolve by maintaining a drainage catheter in the chest for a prolonged period. However, for some patients, additional measures are required to help seal the affected tissue. Known strategies for managing post-operative air leak include placing one-way valves, surgical revision, and chemical pleurodesis. Chemical pleurodesis involves injecting an irritant through the chest drainage catheter to promote sealing of the leaking lung tissue. While many agents exist for chemical pleurodesis, a relatively new method for treating an air leak is by using dextrose solution. Dextrose is appealing due to low cost and availability. Dextrose solution has shown some efficacy in other countries and undergone Phase 1 clinical investigation in Canada to show its safety and dosing recommendations. In this study, our aim is to compare the effectiveness of using dextrose solution for treating post-operative air leak compared to usual care with chest tube drainage alone.

This clinical trial will evaluate a multi-level scalable intervention called Improving Dementia Care (IDC). The investigators hypothesize that IDC will increase dementia detection in patients with impaired cognition more than the control condition, Enhanced Usual Care (EUC), over 6 months.