Chapel Hill

Researchers are investigating the use of 19F MRI, a novel imaging technique using inhaled perfluoropropane gas combined with magnetic resonance imaging, to visualize lung ventilation in children and adolescents aged 6 to 17 years. This method has not been studied in children before. The study compares children with cystic fibrosis who have normal lung function to healthy children of the same age to assess the feasibility of this imaging approach in a pediatric population. All participants will inhale perfluoropropane gas during MRI scans using two techniques standard breath hold and a newer free-breathing method that eliminates the need for breath holds. Each participant will breathe the gas for five breath hold cycles, with volume adjusted for lung size. This cross-sectional study includes both children with mild cystic fibrosis lung disease and healthy controls undergoing the same procedures. Participants will be evaluated during a single visit where they will undergo the MRI procedures along with spirometry and multiple breath nitrogen washout tests. Researchers will measure participation and completion rates as well as parental and child acceptability of the procedures. They will also analyze MRI-derived ventilation defect parameters and lung volumes to compare lung function between groups. The study aims to complete recruitment within two years, with assessments focused on the feasibility and sensitivity of these imaging and lung function measures.

Essential tremor ET is a common neurological disorder that can cause significant functional and psychological difficulties, often resistant to oral medications. Researchers are investigating a new approach called 3-D tractography Vim-Focused Ultrasound Ablation Vim-FUSA, which uses advanced brain imaging to better target the area responsible for tremors. This study aims to compare this new method with the standard Vim-FUSA technique and evaluate its safety, feasibility, and effectiveness in both animal and human studies. The treatment involves using focused ultrasound guided by magnetic resonance MR imaging and 3-D tractography to precisely ablate 70% of the ventral intermediate nucleus Vim in the brain. The procedure includes head preparation, placement of a stereotactic frame, pre-surgery imaging, exploration with low-dose sonications, and therapeutic sonications to deliver the ablation while monitoring tremor and side effects. The study includes an experimental animal phase comparing the new and standard methods and a human phase assessing 24 participants before treatment and three months after. Participants will undergo assessments including videotaped tremor evaluations at baseline and three months post-treatment, with blinded comparison to matched controls. Researchers will use intraoperative MR imaging to distinguish treated tissue from swelling and predict clinical outcomes. Safety, side effects, quality of life related to tremor, and participant satisfaction will also be monitored. Overall participation lasts at least three months, with careful follow-up to evaluate treatment effects and safety.

Researchers are evaluating the safety, tolerability, and early effects of 4D-710, an investigational gene therapy, in adults with cystic fibrosis CF lung disease who cannot use or tolerate existing CFTR modulator therapies. A sub-study also includes adults with advanced CF lung disease or frequent lung flare-ups who are currently on CFTR modulator therapy. This Phase 12 open-label trial aims to find appropriate dosing and assess potential benefits for these patient groups. Participants receive a single inhaled dose of 4D-710, which is a gene therapy designed to deliver a corrected version of the CFTR gene to lung cells. The study includes a dose exploration phase for those ineligible for modulator therapy, a dose expansion phase at selected doses, and a sub-study for participants on modulator therapy receiving various doses. Each participant undergoes one administration of the therapy during the trial. Throughout the study, participants are monitored for adverse events over a 60-month period. Evaluations include lung function tests, oxygen saturation measurements, and tracking of pulmonary exacerbations. Participants maintain their existing treatments if applicable, and researchers assess safety and early signs of effectiveness. The total study duration extends up to approximately nine years, including long-term observation after dosing.

Researchers are evaluating new medicines to prevent HIV-1 Human Immunodeficiency Virus Type 1 infection. This Phase 3 clinical study aims to determine if taking the drug MK-8527 once a month can prevent HIV-1 infection as well as or better than the standard daily pre-exposure prophylaxis PrEP. The study also assesses the safety and tolerance of MK-8527 in participants. Participants are randomly assigned to one of two groups. One group receives 11 mg of MK-8527 once monthly along with a daily placebo pill matching FTCTDF. The other group receives a daily dose of FTC245 mg TDF and a monthly placebo matching MK-8527. This treatment period lasts for approximately two years, followed by an additional 28-day period where all participants receive open-label FTCTDF daily. During the study, participants will undergo regular monitoring to check for HIV-1 infection and any adverse events. Researchers will track the number of participants who acquire HIV-1, experience side effects, or stop treatment due to side effects over the two-year period. Safety and adherence assessments will be conducted to evaluate the study treatments. The total participation time includes the two-year treatment phase plus the 28-day follow-up with open-label FTCTDF.

Researchers are evaluating treatments for germinal center B-cell-like diffuse large B-cell lymphoma GCB DLBCL, a fast-growing blood cancer affecting immature B-cells. The study compares two treatment combinations to see if more people respond to zilovertamab vedotin MK-2140 plus R-CHP versus polatuzumab vedotin plus R-CHP. This Phase 2 trial aims to assess the effectiveness and safety of these regimens in participants with newly diagnosed GCB DLBCL. Participants receive either zilovertamab vedotin along with rituximab, cyclophosphamide, doxorubicin, and prednisone R-CHP, or polatuzumab vedotin combined with R-CHP. Treatments are given by intravenous infusion on Day 1 of each 3-week cycle for up to 6 cycles, approximately 4 months, with prednisone or prednisolone taken orally for 5 days of each cycle. For participants with high-risk DLBCL, up to 2 additional cycles of rituximab or biosimilar are given. During the study, participants are monitored for response to treatment using Lugano Response Criteria, with follow-up lasting up to about 31 months for the primary outcome. Secondary outcomes include progression-free survival, overall survival, event-free survival, duration of complete response, adverse events, and quality of life assessments. Safety and health status are regularly checked through exams, lab tests, and questionnaires over several years, with total study participation extending up to 7 years.

Researchers are evaluating whether combining HIV-specific broadly neutralizing antibodies bNAbs with antiretroviral therapy ART in adults newly diagnosed with acute HIV infection AHI is safe and can delay viral rebound compared to ART alone. This phase II, randomized, double-blind, placebo-controlled study aims to assess the impact of this combination on viral load, immune response, and viral reservoirs. The study is sponsored by the National Institute of Allergy and Infectious Diseases NIAID. Participants are randomly assigned to receive either a combination of two bNAbs, VRC07-523LS and PGT121.414.LS, given as intravenous infusions once at study entry alongside daily oral ART, or a placebo infusion with daily ART. The study involves several steps, including treatment initiation, analytic treatment interruption, and monitoring phases. The bNAbs are administered intravenously at specific doses over 15 to 60 minutes at enrollment. ART consists of a daily oral tablet containing bictegravir, emtricitabine, and tenofovir alafenamide. During the study, participants attend scheduled visits for safety assessments, blood tests measuring viral load and immune cells, and monitoring for side effects or adverse events. Researchers track the time to viral rebound after stopping ART, changes in immune cell counts, and drug levels in the blood. Participants who meet criteria for restarting ART will do so and continue to be monitored. The total participation includes treatment and follow-up periods, with close observation to evaluate safety and treatment effects up to 24 weeks after ART interruption.

Researchers are studying the safety and effects of VHB937 in people with early Alzheimers disease, including those with Mild Cognitive Impairment due to Alzheimers or mild Alzheimers itself. This randomized, double-blind, placebo-controlled Phase II trial aims to evaluate whether VHB937 can benefit memory, thinking abilities, daily functioning, and brain changes. The study also looks at how the body processes VHB937 and responds to it. Participants receive intravenous infusions of either a low dose or high dose of VHB937, or a placebo, over a 72-week double-blind period. After this, an extension phase follows for further observation. The treatments are given through infusions, and participants are randomly assigned to one of the three groups in parallel. Throughout the study, participants and their study partners attend regular visits for assessments including clinical dementia rating scales, cognitive tests, daily living activities evaluation, and brain imaging biomarkers. Safety is monitored by tracking adverse events and serious adverse events. Blood samples are collected to measure VHB937 levels and immune responses. The total study duration includes the 72-week treatment period plus additional time in the extension phase.

Researchers are evaluating a decisional support intervention called the University of Rochester-Geriatric Oncology assessment for Acute Myeloid Leukemia UR-GOAL compared to an attention control among older adults newly diagnosed with acute myeloid leukemia AML. This multicenter randomized controlled trial aims to assess whether UR-GOAL can reduce patient distress, improve shared decision making between patients, caregivers, and oncologists, and decrease decisional conflict. The study is sponsored by the University of Rochester and is conducted at four sites. Participants will be randomly assigned to one of two groups the UR-GOAL intervention or an attention control group. Patients in the UR-GOAL group will watch an AML-focused video, complete a best-worst scaling exercise to identify their care priorities, and receive a summary report to review and discuss during clinical visits. Caregivers, if available, will also watch the AML video and receive the summary report. Oncologists will receive a report summarizing the patients geriatric assessment, priorities, and prognosis perception. The control group patients and caregivers will watch a nutritional video, complete a nutrition questionnaire, and receive nutrition handouts for review and discussion. Oncologists in this arm will be provided with the patients nutrition questionnaire. Both arms involve reviewing these materials during upcoming clinical visits. Participants will be assessed at several time points including 1 month for distress, 2 weeks for shared decision making and decisional conflict, and observation of shared decision making at the start. All participants must be 60 years or older with a new AML diagnosis and have not started cancer-directed treatment except some temporary measures. The study involves questionnaires, videos, and discussions to measure decision-related outcomes. The total study duration extends to June 2030, with ongoing monitoring of patient distress and decision-making quality. Caregivers and oncologists also participate in aspects of the assessments and interventions.

Researchers are evaluating zorevunersen, an investigational antisense oligonucleotide drug, in children with Dravet syndrome, a rare and severe form of epilepsy. This Phase 3, global, multicenter, randomized, double-blind, sham-controlled study aims to assess the efficacy, safety, and tolerability of zorevunersen by measuring changes in major motor seizure frequency and other important aspects such as behavior, cognition, clinical status, and quality of life. Participants will be randomly assigned to receive either zorevunersen or a sham procedure during Treatment Period 1, which lasts about 52 weeks. Zorevunersen is given by intrathecal injection at specific doses and intervals throughout this period. After Treatment Period 1, all eligible patients enter Treatment Period 2, where everyone receives zorevunersen for additional dosing over several months. Patients who complete the study may have the chance to join an open-label extension to continue receiving the drug. During the study, participants will undergo regular assessments including seizure monitoring, behavioral and cognitive evaluations, and health-related quality of life measurements. The primary outcome is the change in major motor seizure frequency at Week 28, with secondary outcomes assessed at Week 52. Safety and tolerability are also closely monitored. Overall participation lasts through both treatment periods and possible extension, with detailed follow-up to evaluate the drugs potential for disease modification.

Researchers are studying an experimental drug called REGN10597, given alone or with another drug called cemiplimab, in adults with advanced solid tumors such as melanoma and clear-cell renal-cell carcinoma. This Phase 12a trial aims to evaluate how safe, tolerable, and effective these study drugs are in treating cancers that have spread in the body. The study also explores side effects, drug levels in the blood, and whether the body produces antibodies against the drugs that might affect their activity or cause side effects. Participants receive REGN10597 alone or combined with cemiplimab in different dose levels to find the best dose for future studies. The study includes dose escalation and dose expansion phases, with separate groups for melanoma and renal-cell carcinoma patients. Dosing and administration follow the study protocol, and participants may have biopsies at screening and other times for research purposes. During the study, participants will be monitored closely for side effects and treatment responses. Researchers assess tumor response using established criteria and track various safety outcomes over approximately six years. Blood samples are collected to measure drug concentrations and antibody development. Participants will have regular visits for evaluations, and their health status will be followed for a long-term period to understand treatment effects and safety.