Clinical trials

Older survivors of blood cancer are at a high risk of accelerated biological aging, which increases their risk of developing multiple aging-related conditions. Whereas physical exercise can improve overall health, older cancer survivors do not meet the recommended physical activity, highlighting the need to develop behavioral interventions to increase adherence. Several other knowledge gaps exist to implement exercise interventions in older survivors of blood cancer; the dose and duration of exercise necessary to slow biological aging in older blood cancer survivors remain unknown. To bridge these gaps in knowledge, we have designed a Phase 2 randomized control trial to test the effects of behavioral and exercise interventions on various outcomes.

This phase 2/3 randomized trial evaluates whether dose escalation to the dominant intra-prostatic lesion (DIL) compared to whole gland dose escalation during prostate stereotactic body radiotherapy (SBRT) results in differences in genitourinary (GU) and gastrointestinal (GI) toxicities.

The iCaRe2 is a multi-institutional resource created and maintained by the Fred \& Pamela Buffett Cancer Center to collect and manage standardized, multi-dimensional, longitudinal data and biospecimens on consented adult cancer patients, high-risk individuals, and normal controls. The distinct characteristic of the iCaRe2 is its geographical coverage, with a significant percentage of small and rural hospitals and cancer centers. The iCaRe2 advances comprehensive studies of risk factors of cancer development and progression and enables the design of novel strategies for prevention, screening, early detection and personalized treatment of cancer. Centers with expertise in cancer epidemiology, genetics, biology, early detection, and patient care can collaborate by using the iCaRe2 as a platform for cohort and population studies.

The goal of this supportive care study is to learn if high-dose Vitamin E and CoQ10 in combination can reduce the negative sub-acute and chronic side effects of radiation to the pelvis in adults treated for prostate, uterine, cervical, or anal cancer. The main questions it aims to answer are: * Is taking high doses of Vitamin E (dl-α-tocopherol acetate, 900mg) and CoQ10 (ubidecarenone, 200 mg) each day safe and tolerable? * Does a 90-day course of vitamin supplementation with high-dose Vitamin E and CoQ10 reduce the incidence and severity of late radiation-associated toxicities? * Does high-dose vitamin supplementation with Vitamin E and CoQ10 improve patient reported measure of quality of life? * Does high-dose vitamin supplementation with Vitamin E and CoQ10 change the trajectory of recovery after radiation therapy? * Is there evidence that suggests high-dose vitamin supplementation with Vitamin E and CoQ10 impairs oncologic outcomes? * Can longitudinal biomarkers of oxidative stress be correlated with Vitamin E and CoQ10 concentrations or radiation-associated toxicity? * Will subjects adhere to the vitamin administration schedule? * Are there demographic differences in systemic exposure to the vitamins? * Are there differences in toxicity outcomes across tumor types or radiation dose fractionation schemes? Participants will be asked to: * Take Vitamin E and CoQ10 every day for 90 days by mouth. * Fill out quality of life questionnaires to assess treatment impacts. * Come for clinic visits every 2-4 weeks for around 4 months, then every 3-6 months for around 2 years. * Have blood draws more frequently than standard-of-care for clinical laboratory examinations and the collection of research samples. * Undergo Computed Tomography (CT) imaging of the chest, abdomen, and pelvis more frequently than standard of care. * Agree to lifestyle changes that ensure adequate vitamin absorption including intermittent abstinence from alcoholic beverages.

Peripheral artery disease (PAD) is associated with elevated oxidative stress, and oxidative stress has been implicated as the cause of reduced endothelial reactivity in individuals with PAD. Endothelial function is important because the endothelium contributes to the dilation of arteries during exercise, thereby implicating impaired endothelial function as a mechanism contributing to exacerbated exercise-induced ischemia. Therefore, the purpose of this study is to test the hypothesis that acute exogenous diroximel fumarate (Vumerity) intake will improve antioxidant capacity, thereby reducing oxidative stress and improving vascular function and walking capacity in those with PAD. During this study, participants will be administered diroximel fumarate or a placebo, and the acute effects of diroximel fumarate on vascular function and walking capacity will be assessed. Vascular function and walking capacity will be assessed with flow-mediated dilation, arterial stiffness, head-up tilt test, blood biomarkers, near-infrared spectroscopy, and a treadmill test. There will be a follow-up visit to assess blood work after diroximel fumarate.

Rheumatoid arthritis (RA) is a common disease with approximately 1% prevalence. RA is also a chronic, progressive disease with no cure. Current treatment goals are to minimize pain, limit joint damage, and prevent loss of function. Drugs used to treat RA include non-steroidal anti-inflammatory drugs (NSAIDS), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs), including biologics. Methotrexate (MTX) is the DMARD of choice in the treatment of RA, because it has been shown to be both well-tolerated and effective in achieving clinical response and slowing radiographic progression of disease. However, this drug alone results in remissions in only a small subset of patients and reliable predictors of DMARD response have yet to be identified. This study is open-label of 16-weeks duration to identify factors that help predict clinical responses to disease-modifying antirheumatic drugs (DMARD) therapies for rheumatoid arthritis (RA) participants. All participants will receive a starting dose of DMARD medication(s) which may be adjusted by the investigator as needed. If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator. Necessary withdrawals prior to week 16 visits will be considered end of study. Otherwise, end of study data as well as study serum will be collected at week 16. A portion of the blood collected at baseline, week 8 and week 16 for the optional addendum portion of the study is for future research and will be utilized attempting to look to detect the generation of superoxide radicals. These radicals have been shown to be associated with inflammation and may correlate with the progression of RA, which if confirmed, should decrease the levels of these radicals signaling response to treatment.

Problem: Clear aligner therapy is widely used in orthodontics due to improved periodontal outcomes compared to fixed appliances. However, composite attachments are frequently bonded to molars to enhance biomechanics, potentially creating plaque-retentive areas that may increase localized inflammatory responses. Currently, no studies have directly compared periodontal inflammatory biomarker levels in molars treated with clear aligners with versus without attachments. This gap limits understanding of the biological impact of attachments on periodontal tissues.Hypothesis:First molars treated with clear aligners and composite attachments will demonstrate higher levels of inflammatory biomarkers in gingival crevicular fluid (GCF) compared to molars treated with clear aligners without attachments. Biomarker levels are expected to be lower in the non-attachment group. Methods: This study will include 30 orthodontic patients divided into two groups (15 per group):1. Clear aligners with molar attachments 2. Clear aligners without molar attachments. GCF samples will be collected from first molars at a routine orthodontic appointment at the UNMC College of Dentistry Graduate Orthodontic Clinic. Primary biomarkers include IL-1β, IL-6, TNF-α, and MMP-8 measured via ELISA. Clinical periodontal parameters (Plaque Index, Gingival Index, Bleeding on Probing, Probing Depth) will also be recorded.

This study is developing and testing a new controller for a robotic ankle exoskeleton (Biomotum) that can adjust itself in real time to better support people while they walk. The system learns how each person moves and automatically changes the amount and timing of assistance to make walking feel easier and more efficient. By using information from the person wearing the device, the exoskeleton can quickly find the level of support that works best for them. The long-term goal is to create personalized walking assistance that can help people with mobility limitations move more comfortably and with less effort.

The goal of this randomized controlled study is to test if this new intervention works to help adolescents quit vaping. A key feature of the program is the use of peer support for parents, delivered by trained parent coaches. Participants will complete baseline and follow up surveys. Parents in the intervention arm will receive peer support as part of the program.

The goal of this randomized clinical trial is to evaluate the effectiveness of a collaborative care intervention, consisting of remote blood pressure monitoring and support from community health workers, in improving blood pressure control and reducing postpartum complications among Black women with hypertensive disorders of pregnancy (HDP). The primary objectives are to determine whether the intervention leads to improved blood pressure control at 12 months postpartum compared to standard care, and whether it reduces the incidence of serious maternal morbidity, including hospitalizations and cardiovascular events. Secondary objectives include examining whether patient activation and trust in the healthcare system mediate the relationship between the intervention and clinical outcomes. Participants will be enrolled at approximately 6 weeks postpartum and randomized to either the collaborative care intervention or standard postpartum care. All participants will self-monitor blood pressure using a provided device, receive guidance on hypertension management, and complete study assessments at multiple time points. Participants assigned to the intervention arm will additionally receive ongoing support from community health workers, including health education, care coordination, and assistance with healthcare navigation. Clinical outcomes and patient-reported measures will be assessed over a 12-month follow-up period.

The objective of this pilot study is to assess the feasibility and performance of real-time CGM for titrating CII via: (1) evaluation of CGM glucose accuracy in oncology and post-transplant population receiving IV insulin therapy, and (2) assessing both nursing acceptance/convenience and patient satisfaction with CGM use. A randomized prospective trial model will be used comparing glucose control (glucometrics hypoglycemia), patient experience and nursing satisfaction in cancer patients receiving IV insulin therapy where monitoring is done via: a) hybrid protocol originally developed by Faulds et al. integrating CGM with periodic POC-BG tests to monitor and ensure the ongoing accuracy of CGM measurements (available at http://www.covidindiabetes.org). b) standard care with hourly POC testing and blinded professional CGM.Inclusion criteria: Eligible patients include oncology and post-transplant patients receiving IV insulin therapy while on corticosteroid treatment and receiving specialized nutrition. Exclusion criteria: medically instable patients receiving pressor therapy and ICU level of care. Outcome evaluation; Patients' characteristics were collected through the EHR. Glucometrics will be collected throughout the study to include mean BS, % in range ( 80-180) , patient day hypoglycemia , patient stay hypoglycemia . Nursing surveys: Survey will be provided for nurses to assess nursing burden, acceptability. Nurses will complete a survey before starting the project and again after being involved in the initial and ongoing validation phases of CGM at the end of the project. The purpose is to report their convenience with using CGM and their preferred glucose monitoring method, which included POC arterial blood, POC finger sticks, and CGM. Nursing surveys will be administrated electronically to nursing staff and the results will be uploaded automatically. Patient survey: Patients will be approached by the team members to inquire about the willingness to provide feedback. The questionnaire will assess their experiences of care with CGM (options: very good, good, fair, poor), glucose check without pain and disruptions of sleep (yes/no), and overall confidence of care with CGM process (very confident, quite confident, somewhat confident, little confident). Patient surveys will handed out by the team members, and the results were subsequently entered into database (See both nursing and patient surveys in Supplementary Material.)

Enhanced Recovery After Surgery (ERAS) protocols have been of increasing interest in the surgical community for decades. The emphasis has been development of protocols to maximize pain control post-operatively without the use of opioids. While this approach has been studied extensively in the oncology surgery literature, little data exists on the utility of ERAS protocols in the setting of breast conserving surgery (BCS), which is a type of surgery to remove breast cancer while saving as much of the breast as possible. The purpose of this study is to determine the utility of implementing ERAS protocols in breast cancer patients undergoing breast conserving surgery. Study participants will be randomized to either ERAS protocol or standard peri-operative care without ERAS. The study will assess the how many opioid prescriptions are given in the first week after surgery and how much pain participants report right after surgery. Investigators will also look at how long participants stay in the recovery room and if medicine for nausea is needed.

1\) The purpose of this study is to assess segmental pulse arrival time (PAT) as an alternative biomarker to detect lower-extremity peripheral artery disease (PAD), and to investigate the impacts of local skin heating and foot elevation. The secondary purpose will be to investigate the impacts of age on segmental PAT. The subject population will include any adults 19 years of age or older with or without PAD. Exclusion criteria include having an aortic aneurysm with or without previous intervention, previous revascularization surgeries of the arteries in the legs/aorta, walking impairments independent of PAD, gangrene or ulcers of the toes/feet, and currently pregnant or breastfeeding. 3) All aims of the present study will be completed with a single laboratory visit. Descriptive measurements will include height, weight, age, sex, body fat percentage, and self-reported medication and health history. Subjects will lie in the supine position for 20-min. After rest, either the ankle-brachial index (ABI) or PAT will be assessed. After 10-min of further rest, the other measurement will be performed. ABIs will be assessed according to current guidelines: blood pressures will be assessed in the dorsal pedis and tibialis posterior arteries of both legs and the brachial arteries of both arms using a blood pressure cuff and Doppler ultrasound. PAT will be simultaneously assessed in both arms and legs using an investigational device with a 3-lead electrocardiogram sensor and four photoplethysmography (PPG) sensors. A PPG sensor will be applied to a finger on each hand and both big toes. Signals will be collected for 15-min with finger and toe sensor temperatures at 30 C. Toe sensor temperature will then be elevated to 45 C for 15-min. Finally, toe sensor temperature will remain at 45 C, and the feet will be elevated 8-in with a soft cushion for 15-min. Blood pressure in the arm and legs will be assessed at the end of each stage. Thermal images of the fingers and toes will be assessed before using the investigational device and after each stage. Subjects will then participate in a 6-min walking test (6MWT) to objectively establish walking capacity. The 6MWT will be performed in accordance with current guidelines. Segmental PATs will be compared with ABI and 6-min walking time to determine if segmental PATs can predict lower-extremity PAD (ABI) and the associated walking impairment (6MWT). This study is expected to last \~2.5hrs. 4) There will be no follow-up.

Pancreatic mucinous cystic neoplasm (MCN) is a precursor to invasive pancreatic adenocarcinoma which occurs almost exclusively in females in their 5th-7th decade. Currently the only option for MCN treatment and prevention of invasive pancreatic ductal adenocarcinoma (PDA) is oncologic resection. The clinical features of pancreatic MCN support the influence of sex hormones in the pathogenesis of the disease. Anti-hormonal therapy may therefore constitute an effective approach to treatment. Preliminary analyses from preclinical studies suggest that tamoxifen inhibits the spread and normal life cycle in MCN epithelial cells and fibroblasts. Investigators hypothesize that in humans, treatment with tamoxifen will lead to cyst regression or stabilization and may spare or delay the need for resection. Up to 15 participants not undergoing immediate resection will be enrolled and take tamoxifen orally for up to 24 weeks. The study will assess the feasibility of tamoxifen as a treatment for pancreatic MCN.

This prospective feasibility study evaluates a minimal residual disease (MRD)-adapted treatment strategy in patients with diffuse large B-cell lymphoma (DLBCL) receiving frontline chemoimmunotherapy. Circulating tumor DNA (ctDNA)-based MRD testing and interim positron emission tomography (PET) imaging after two cycles of therapy are used to guide treatment decisions. Patients with detectable MRD may receive low-dose radiation therapy (LDRT) to residual PET-avid disease sites in addition to standard systemic therapy, while patients with undetectable MRD continue standard frontline chemoimmunotherapy. The study aims to assess the feasibility and safety of integrating MRD-guided radiation therapy into frontline treatment of DLBCL.

Anterior Cervical Discectomy and Fusion (ACDF) is a widely performed surgical procedure used to treat cervical spondylosis and cervical disc herniations with cervical nerve root compression and or cervical spinal cord compression when conservative treatment options have been exhausted. The primary aim of ACDF is to alleviate neck, shoulder, and upper extremity pain associated with degenerative cervical disc disease by removing one or more affected discs, decompressing the nerves, and restoring cervical spine anatomy through the implantation of structural allograft/autograft bone or artificial spacers, plates, and screws. Historically, ACDF has demonstrated substantial long-term benefits in pain relief and quality of life improvements for patients. In the United States alone, the annual number of ACDF procedures exceeds 150,000 and is projected to rise significantly over the next four decades. Despite its technical complexity, ACDF is considered a relatively safe procedure. Common postoperative complications include dysphagia (1.7-9.5%), hematoma (0.4-5.6%), worsening myelopathy (0.2-3.3%), recurrent laryngeal nerve palsy (0.9-3.1%), cerebrospinal fluid leakage (0.5-1.7%), and surgical site infections (0.9-1.6%). One strategy employed to mitigate postoperative complications such as hematoma, surgical site infection, and the need for reoperation is the placement of an indwelling subfascial drain within the surgical site. These drains facilitate the removal of accumulated blood or serous fluid, thereby reducing localized pressure and potentially preventing adverse outcomes. Despite its theoretical benefits, the utility of subfascial drains remains a topic of debate among surgeons. Given the limited evidence on the efficacy of subfascial drain placement following ACDF, this study proposes a randomized controlled trial to evaluate the necessity and impact of subfascial drain placement on postoperative outcomes. This study will determine whether subfascial drain placement reduces the incidence of postoperative complications, including hematoma, infection, airway compromise and secondary surgeries, compared to no drain placement following ACDF surgery; assess the impact of subfascial drain placement on the severity and duration of postoperative dysphagia compared to no drain placement; and evaluate participant-reported outcomes and satisfaction, including postoperative pain and recovery experience, between the drain and no-drain groups.

This study will examine the coagulation and fibrinolysis profiles of those with autoimmune skin diseases. Blood samples will be collected from participants with active/poorly controlled immune-mediated skin diseases and mild/latent/well-controlled immune-mediated skin diseases. A one-time sample from 15 general dermatology outpatients who do not have a known or suspected diagnosis of bullous diseases, immune-mediated dermatologic condition, or cutaneous malignancy will also be collected to serve as control. Blood samples from both participant populations will be analyzed for coagulation and inflammatory markers and compared. The results of this study may help inform future studies on the utility of analyzing coagulation and fibrinolysis profiles of patients with autoimmune skin diseases.

The goal of this study is to see if gentle electrical stimulation can help children with cerebral palsy (CP) walk more easily. This stimulation, called neuromuscular electrical stimulation (NMES), sends small pulses to muscles to help them activate. Researchers will test different ways of using NMES to find out which method works best. Participants will walk on a treadmill at a comfortable speed while NMES is applied to leg muscles. The study will compare different stimulation settings to see which one helps the most.

The goal of this observational and interventional study is to understand how therapeutic deep brain stimulation (DBS) affects attention, perception and cognition in participants with Parkinson's disease (PD) and non-PD movement disorders, including essential tremor (ET) and dystonia (DT). The main questions it aims to answer are: * Does impaired control of attention and eye movement in PD alter how social cues are perceived and interpreted? * Does therapeutic DBS improve or worsen attentional and perceptual deficits for social cues in PD, ET and DT? * Can DBS be optimized to restore normal attentional control in PD while remaining an effective therapy for other aspects of the disorder. * What do parts of the brain targeted by DBS contribute to the control of attention? Using an eye tracking camera, investigators will study how participants with PD, ET and DT look at and perceive facial expressions of emotion before and after starting DBS therapy, in comparison to a group of healthy participants without ET, PD, DT or DBS. Participants with PD, ET and DT will see and rate morphed facial expressions on a computer screen in three conditions: * Before starting DBS therapy (over approximately 1 hour). * In the operating room, during the standard procedure to implant DBS electrodes, while the participant is awake (for no more than 15 minutes). * After starting DBS therapy, with brief experimental changes of DBS stimulation level and frequency (over approximately 1 hour).

More than 15 million family caregivers provide support for individuals with Alzheimer's disease (AD) or related dementias. This number is expected to grow with the increasing population of persons with dementia (PWD). Stress in caregivers to older adults with chronic diseases is already a significant public health issue because it is associated with multiple negative physical and mental health outcomes for the caregiver (e.g., depression, cardiovascular disease) and can negatively impact the health of the PWD as well. Importantly, stress levels are even higher in female than male caregivers and in caregivers to PWD than other chronic conditions that affect older adults. There are numerous interventions to improve well-being in caregivers to PWD, but only two have been shown to moderately improve caregiver depression and quality of life in the PWD. However, both of the interventions are time and energy intensive. One promising candidate to reduce stress and improve quality of life is the endogenous neuropeptide oxytocin (OXT). Intranasal OXT interventions have been shown to successfully reduce stress and increase quality of life in other populations, including patients with borderline personality disorder, Post-traumatic Stress Disorder (PTSD), Anxiety Disorder, and Depressive Disorder. This study will assess the efficacy and safety of intranasal oxytocin (OXT) to improve the quality of life and reduce chronic stress levels in the caregivers to PWD. Participants will be randomly enrolled to one of three groups: 12 IU intranasal oxytocin, 24 IU intranasal oxytocin or placebo. The study drug will be administered daily for 21 days.

This study is being done to see if adding GLIADEL to the site where the tumor was removed works as well as just having the tumor removed with radiation treatment done within six weeks after the surgery to keep the cancer from coming back.

Higher gut microbiome diversity has been associated with improved survival following autologous stem cell transplantation in multiple myeloma and lymphoma. This study hypothesises that prebiotic supplementation with resistant starch (RS) will improve gut microbiome diversity at time of stem cell engraftment. To test this, participants will either have RS or a placebo (maltodextrin) mixed into a food item of their choice for approximately 10 days prior to stem cell infusion and continue to the first day of neutrophil engraftment. The study will look at the difference in gut microbiome diversity between the RS and placebo arm collected at the engraftment timepoint, dietary evaluation to assess the impact of subject diet on microbiome response to intervention and serum sample collection to assess differences to gut permeability during transplant.

Purpose: Prospective, single-site Phase II study testing whether PSMA-PET/MRI-guided, de-escalated salvage radiation reduces acute Grade ≥2 toxicity versus a 44% historical rate, while maintaining cancer control after prostatectomy.Population/Eligibility: Adult men ≥30 years with prior radical prostatectomy and biochemical persistence/recurrence per NCCN (persistent positive PSA after RP, or undetectable PSA that becomes detectable and rises on ≥2 determinations, or PSA \>0.1 ng/mL). Must have a targetable PSMA-avid lesion in the prostate bed and/or pelvic lymph nodes and/or an MRI-defined lesion suspicious for local recurrence. KPS ≥80 or ECOG ≤2; life expectancy \>5 years; able to consent. Exclude: Evidence of distant metastatic disease outside pelvic nodes (including osseous involvement), conditions that preclude radiation, or factors preventing protocol compliance.Interventions \& Evaluations: Baseline history/physical, vitals, performance status, labs (PSA, CBC w/diff, CMP/creatinine), pelvic MRI and PSMA-PET/CT; optional biopsy if feasible. External beam radiation therapy (LINAC/VMAT) with daily image guidance: pelvis 45 Gy in 25 fractions, followed by a sequential boost to PSMA/MRI-defined disease to 63-70.2 Gy in 10-14 additional fractions, with protocolized OAR constraints. All participants receive standard-of-care androgen deprivation therapy (ADT) for 6-24 months at the treating clinician's discretion. Weekly on-treatment visits; physician-assessed toxicities graded by CTCAE v5. Patient-reported outcomes (IPSS; FACT-P) at baseline and each in-person follow-up.Follow-up: Phone toxicity check 1 month post-RT; clinic at 4 months post-RT, then every 3 months thereafter until 24 months after completion of ADT. At each visit: H\&P, CTCAE toxicity assessment, and PSA. If biochemical failure occurs, imaging (PSMA-PET/CT, CT and/or MRI) is obtained per standard of care to assess clinical progression.Endpoints/Design: Primary endpoint: acute (≤4 months post-RT) Grade ≥2 toxicity (all types). Secondary endpoints: 2-year biochemical progression-free survival; chronic toxicity and patient-reported outcomes from 4-24 months; 24-month local control, locoregional control, distant metastasis, and overall survival. Simon optimal two-stage design with interim analysis after the first 18 patients complete RT (stop if ≥8 have Grade ≥2 acute toxicity); total planned enrollment up to 54.

Hyperbaric Oxygen Therapy (HBO) is routine treatment of carbon monoxide (CO) poisoning to prevent delayed neurological sequelae. This study looking to see if neurologic outcomes are improved with the addition of dexamethasone. CO poisoning can initiate a free radical mediated process that can instigate a demyelinating process resulting in long term neurological sequelae in some, but not all patients. In other demyelinating disorders, steroids are a part of first line treatment. HBO is already used for acute CO poisoning, so this pilot study will try to ascertain if the addition of steroids in concert with each hyperbaric oxygen session will yield improved outcomes.

Glioblastoma (GBM), WHO grade IV glioma, represents the majority of adult malignant primary brain tumors, with an incidence of 2-3 per 100,000 person-years. The survival for GBM has increased in the last decade but is still low with a median survival of 15-18 months. Recurrence after initial standard therapy, radiation therapy and chemotherapy with temozolomide, few options are available. Even with further therapy, median progression free survival at 6 months after first relapse (PFS-6) is only 15%. Similarly, anaplastic astrocytoma and anaplastic oligodendroglioma, grade III gliomas, once recurrent after radiation therapy and first-line chemotherapy, have identical therapeutic options and poor outcomes with PFS-6 of 31%. Temozolomide (TMZ) has a favorable side effect profile and is available orally, however, cytotoxicity occurs. Metronomic temozolomide at low doses on a continuous schedule, have demonstrated better survival in studies. This study will determine the recommended dose and the side effects of PCI-24781/Abexinostat with metronomic temozolomide.