This study facilitates the collection and analysis of outcome data for patients with dyskeratosis congenita (DC) or severe aplastic anemia (SAA) undergoing a hematopoietic stem cell transplant (HSCT). Specific transplant related endpoints include incidence of: -neutrophil engraftment at day 42 and platelet engraftment at 1 year -regimen related morality at 100 days -acute GVHD at 100 days -chronic GVHD at 6 months and 1 year -secondary malignancies

This study will be a multi-site, single-blinded, randomized controlled trial (RCT) that will screen older adults with mild cognitive impairment (MCI) using 4 steps (over the phone, in-person interview including informed consent, medical verification, exercise stress test/magnetic resonance imaging [MRI]). We will enroll 128 participants (target 96 completers, assuming 25% attrition rate at 6 months). After baseline assessment, participants will be enrolled and randomized within age (65-74 years of age or ≥75 years of age) and study site (Minnesota or Rochester) strata centrally at the University of Minnesota (UMN) to one of four groups: ACT, cycling only, SOP only, or control with equal allocation and using a randomization scheme generated by our UMN biostatistician (CI: Vock). Group allocations will be concealed to all investigators and data collectors. The interventions will last for 6 months with 12-month follow-up. Outcomes include: 1) cognition: composite measures of executive function and episodic memory, 2) AD signature cortical thickness: composite using structural magnetic resonance imaging (MRI), 3) functional connectivity in DMN: resting-state using functional MRI (fMRI), 4) aerobic fitness, and 5) clinical and pathological AD conversion. Cognition and aerobic fitness will be assessed at baseline, 3, 6, 12, and 18 months; AD conversion at 6, 12, and 18 months; and AD signature cortical thickness and DMN at baseline, 6, 12, and 18 months. PIs Yu and Lin have developed and tested strategies in their preliminary studies to successfully ensure the protection of human participants.

Supervised exercise training (SET) improves functioning and quality of life for patients with peripheral artery disease (PAD). However, these programs have primarily been conducted in research settings, thus the physical activity that patients complete in real-world settings (urban and rural hospitals) is unknown. The proposed project will use a novel smartphone app called Daynamica, to summarize patients activity patterns and also to enhance patient-study staff communication and subsequently improve PAD patient health outcomes.

The overall objective of this study is to compare the efficacy, safety, immunologic effects, and cost-effectiveness of myeloablative and immunoablative therapy followed by autologous hematopoietic stem cell transplant (AHSCT) versus best available therapy (BAT) over 72 months in participants with relapsing MS and continued MS disease activity despite treatment with DMTs. The primary efficacy objective is to compare MS relapse-free survival, analyzed as time until MS relapse or death from any cause.

This study is a phase III, multicenter, double-blinded, randomized, placebo-controlled trial designed to compare AAT and corticosteroids (CS) to placebo and CS as first line therapy for patients with high-risk acute GVHD. The primary objective of this trial is to compare the rate of complete response (CR) and partial response (PR) on Day 28 post-randomization between AAT and CS versus placebo to match (PTM) and CS in patients with high-risk acute GVHD.

The purpose of this study is to test a new treatment for Alcohol Use Disorder that supports long-term abstinence. This new treatment uses transcranial direct current stimulation (tDCS) combined with cognitive training to decrease the chance of relapse. Additionally, we are interested in examining whether specific genetic differences are related to treatment outcomes. For this, we would collect a saliva sample from you. Providing a genetic sample (saliva) is optional and takes about 5 minutes.

This study will compare the effectiveness and durability of intensive behavioral counseling vs. medical management plus low-intensity behavioral counseling on BMI, body fat, cardiometabolic risk factors, and quality of life in adolescents with severe obesity. We hypothesize that liraglutide plus low-intensity behavioral counseling will elicit superior reductions in BMI (primary efficacy endpoint) and body fat and greater improvements in cardiometabolic risk factors and quality of life compared to intensive behavioral counseling at 56 weeks.

The purpose of this study is to examine the efficacy of a new low-cost Virtual Reality Cognitive Training (VRCT) combined with concurrent cycling intervention called exergame on improving cognition in at-risk community-dwelling older adults at risk for Alzheimer's disease and dementia. We will conduct this study in two phases: Phase I (Feasiblity Testing)aims: Aim1. Develop a prototype exergame that supports integrated, concurrent cycling and VRCT. Aim 2. Examine the feasibility of the exergame in older adults at risk for AD. Phase II (Effect Testing) aims: Aim 1. Develop a fully-featured version of the VRCT aspect of the exergame. Aim 2. Determine the efficacy of the exergame in older adults at risk for AD using an RCT. We hypothesize that cognitive improvement will be greatest for exergame subjects followed by cycling subjects, and least in control subjects. Aim 3. Assess the distraction effect of the concurrent VRCT in exergame on gains in aerobic fitness. We hpothesize that exergame subjects will achieve similar gains in aerobic fitness to cycling only subjects (difference is < 1 standard deviation).

The purpose of this study is to measure levels of blood and brain chemicals related to oxidative stress and inflammation in healthy volunteers and individuals with Type 1 Gaucher disease (GD1) to see if these levels are altered by GD1. We will also examine if there is a change in these blood and brain chemicals after participants begin taking oral N-acetylcysteine (NAC), which is available both as a prescription medication and a natural product that has antioxidant and anti-inflammatory effects.

Study objectives: -To characterize spontaneous and movement-related LFP changes in STN and GP in externalized patients under conditions that modulates the severity of tremor, bradykinesia and rigidity (off meds/off stim; on meds/off stim; off meds/on stim, on meds/on stim). -To characterize and compare the relative effect of different forms of closed loop stimulation (e.g., triggered at specific thresholds of low beta/HFO PAC or beta band activity) to standard isochronal high frequency DBS on motor signs and performance during movement.

The purpose of this study if to determine if stool or blood can be used to detect colon cancers as early or earlier than colonoscopy. The researchers plan to use these samples to learn about specific proteins (also known as biomarkers) that may indicate colon polyps, colon cancer or an increased risk of developing colon cancer. In order to learn more about preventing and detecting colon and rectal cancer, we are collecting samples from subjects with cancer, adenomas, and colonoscopies who may be at risk for polyps.

This partially randomized phase II/III trial studies how well cisplatin and combination chemotherapy works in treating children and young adults (≤ 30 years of age) with hepatoblastoma or liver cancer after surgery. Drugs used in chemotherapy, such as cisplatin, doxorubicin, fluorouracil, vincristine sulfate, carboplatin, etoposide, irinotecan, sorafenib, gemcitabine and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving combination chemotherapy after surgery may kill more tumor cells.

This is an open-label, multi-center, single arm, Phase 1/2 study to evaluate the safety, PK, PD, and efficacy of quizartinib administered in combination with fludarabine and cytarabine (FLA) (Re-Induction Cycles 1 and 2) chemotherapy for re-induction, with optional consolidation chemotherapy, and as a single agent continuation therapy (after optional, but strongly encouraged, HSCT per standard of care), in pediatric relapsed/refractory AML subjects aged ≥1 month old to <18 years old (and young adults up to 21 years old) with FLT3-ITD mutations.

This study will explore the cerebral mechanisms of impaired awareness of hypoglycemia (IAH) in type 1 diabetics (T1D) following exposure to experimental recurrent hypoglycemia (HG). To induce IAH, patients with T1D identified to have normal awareness of hypoglycemia (NAH) will undergo three 2-hour long hypoglycemic clamps. Neurochemical profiles will be measured by high field MRS before and after induction of IAH at a fourth clamp. Participant glycemic variability for ~2 weeks and activity/sleep for ~1 week before the induction of IAH will be monitored as these factors have been shown to alter responses to HG.

This randomized phase III trial studies how well imatinib mesylate and combination chemotherapy work in treating patients (> 1 year and < 21 years) with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia. Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving imatinib mesylate and combination chemotherapy may work better in treating patients with Philadelphia chromosome positive acute lymphoblastic leukemia.

Phase 1 is an observational study to quantify the association between Axillary Web Syndrome (AWS) and metastatic disease and physical impairments such as lymphedema, shoulder dysfunction, and pain comparing patients (iii) with AWS and (iv) without AWS. Phase 2 is a randomized controlled trial to 1) quantify the effects of (i) physical therapy compared to (ii) a control group in individuals with AWS following breast cancer surgery related to physical activity and physical impairments such as lymphedema, shoulder motion, function, and pain (n=44, 22 in each group). Funding to progress to Phase 2 of this trial has been obtained. It is anticipated 120 subjects participating in Phase 1 will be screened for eligibility for Phase 2 (separate consent and eligibility from Phase 1).

Chronic pancreatitis affects as many as 1 in every 2,500 persons and is associated with incapacitating pain, frequent hospitalization and risk of narcotic dependence. This is a debilitating disease with limited treatment options; afflicted patients are often young or middle aged adults. The health and economic costs of pancreatitis are great. One treatment for certain types of chronic pancreatitis is total pancreatectomy with islet autotransplantation (TPIAT). In this procedure, the patient’s pancreas is removed (eliminating the source of the pain) and the patient’s islets, which produce insulin and other important hormones, are harvested from the pancreas and transplanted into the liver thru the portal vein. This procedure is limited by the number of islets removed in the disease pancreas, and problems with the islets functioning normally in the liver. We propose a pilot study to evaluate outcomes when a portion of the islets are placed in an omental pouch (in fatty tissue of the abdomen) to evaluate safety and islet function using this alternative site.

The relapsing nature of Stimulant use disorder is a major obstacle to successful treatment. About 70% of those entering treatment will relapse within one year. To improve treatment outcome, new interventions targeting the underlying brain biomarkers of relapse vulnerability hold significant promise in reducing this critical public health problem. The overarching goal of this project is to expand the traditional expertise in non-invasive neuromodulation at the University of Minnesota towards developing novel paired-neuromodulation approaches using transcranial direct current stimulation (tDCS) for new addiction treatments that support long-term abstinence. This study will allow us to investigate whether the pairing of dorsolateral prefrontal cortex (DLPFC) stimulation and cognitive training can lead to improved treatment outcomes as it pertains to executive functioning and maintenance of abstinence. This paired-neuromodulation approach can potentially be used as a therapeutic intervention to decrease relapse probability in addiction. The long term goal is to develop new addiction treatments that support long-term abstinence.

Background: Distal radius fractures (DRF) account for nearly one-fifth of all fractures in older adults, and women experience them 5x as often as men. Most DRF occur with low impact injuries to the wrist with an outstretched hand, and are often managed via closed treatment and cast immobilization. Women sustaining a DRF are at risk for upper limb immobility, sensorimotor changes, edema and type I complex regional pain syndrome (CRPS). Since CRPS onset is likely influenced by alterations in the brain’s somatosensory region, a rehabilitation intervention, Graded Motor Imagery (GMI), aims to restore cortical representation, including sensory and motor function, of the affected limb. To date, there are no studies on the use of GMI in reducing risk of or preventing the onset of type I CRPS in women with DRF treated with cast immobilization. Due to a higher likelihood of women with this injury developing type I CRPS, it is important to early intervention is needed. Methods/Design: This article describes a six-week randomized comparative effectiveness trial, where the outcomes of a modified GMI program (mGMI) + standard of care (SOC) group (n=33) are compared to a SOC only control group (n=33). Immediately following cast immobilization, both groups participate in four 1-hour clinic-based sessions, and a home program for 10 minutes three times daily until cast removal. Blinded assessments occur within 1 week of cast immobilization (baseline), at three weeks post cast immbolization, cast removal, and at three months post cast removal. The primary outcomes are patient reported wrist/hand function and symptomology on the Patient Rated Wristand Hand Evaluation, McGill Pain Questionnaire, and Budapest CRPS Criteria. The secondary outcomes are grip strength, active range of motion as per goniometry, circumferential edema measurements, and joint position sense. Discussion: This study will investigate the early effects of mGMI + SOC hand therapy compared to SOC alone. We intend to investigate whether an intervention, specifically mGMI, used to treat preexisiting pain and motor dysfunction might also be used to mitigate these problems prior to their onset. If positive effects are observed, mGMI + SOC may be considered for incorporation into early rehabilitation program.

This is a Phase I, multicenter, open-label, dose escalation study to evaluate the safety and tolerability of ruxolitinib when given with fixed dose nivolumab in patients with relapsed or refractory classical Hodgkin lymphoma (cHL). Up to 3 dose levels of ruxolitinib will be tested: 10 mg bid, 15 mg bid, and 20 mg bid. A dose level -1 of ruxolitinib 5 mg bid will be used only if dose level 1 proves too toxic. Participants will receive ruxolitinib at their assigned dose on a 28-day cycle with nivolumab 480 mg IV every 4 weeks until disease progression, unacceptable toxicity or for a maximum of 2 years. Cycle 1 only is expanded to 35 days to permit 1 week of ruxolitinib administration as a single agent before beginning every 4 week nivolumab. The dose escalation will use the continual reassessment method (CRM). The 1st 2 patients will enroll at dose level 1 (ruxolitinib 10 mg twice daily). The next cohort of 2 patients will not begin treatment until the last patient in the current cohort has reach day 35 after the 1st dose of ruxolitinib. Each new cohort of 2 patients will be assigned by the study statistician or designee at the same dose, 1 dose level higher, or 1 dose level lower. Once 10 patients are continuously enrolled at the same dose level, the MTD will be declared. Enrollment will continue at the MTD without staggering until a cumulative total of evaluable 20 patients are treated. Based on resources, the maximum number of allowable evaluable patients is 20. The simulations show it should be sufficient and safe to define the MTD for future efficacy trials. It is expected that 12 patients will be treated at the MTD. A sample size of 12 will achieve 79% power to detect a difference of ORR of 42% (equivalent of 5 responders) vs. null hypothesis of 12% using a two sided exact test with a significance level of 0.05. Participants will continue to receive the drugs until withdrawal criteria are met (e.g. toxicity, disease progression) or until 2 years duration of therapy.

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. The trial is designed as a perpetual platform trial. This means that there is a single Master Protocol dictating the conduct of the trial. The Master Protocol describes the overall framework of the platform trial, including the target population, inclusion and exclusion criteria, randomization scheme, study endpoints, schedule of assessments, trial design, the mechanism for adding and removing interventions, and the statistical methodology and recommended statistical methods for evaluating interventions. Interventions (i.e., investigational products) are tested in trial regimens. Each trial regimen is described in its own Regimen-Specific Appendix (RSA) to the Master Protocol. The RSA will describe the nature of the intervention and its mechanism of action (MoA) including the mode and frequency of administration, dosage, the specific target population (to be selected within the pre-defined subsets of the Master Protocol), additional enrollment criteria (if any), sample size, and other specific intervention-related information and assessments (safety or other assessments that may be in addition to those outlined in the Master Protocol).

Our central hypothesis is that bupropion will prevent postpartum smoking relapse among women who quit smoking during pregnancy. To explore this hypothesis, we will conduct a two-arm, double-blind, placebo-controlled randomized clinical trial using rigorous, validated and reproducible methods that will be implemented by a team of experienced investigators who are familiar with this population. We will enroll pregnant women (n=230) who quit smoking after learning they were pregnant and are motivated to stay abstinent postpartum. Participants will be randomized to receive extended-release bupropion (active 300mg or placebo once daily beginning 4 to 10 days postpartum to 12 weeks post-randomization). All participants will complete the same data collection procedures (e.g., biological sample collection for hormone and cotinine analysis and completion of validated questionnaires) at baseline (gestational week 36), weekly from 4 to 10 days postpartum through 12 weeks post-randomization and at weeks 12, 24, 36 and 52 post-randomization. Intervention adherence will be confirmed quantitatively via high-performance liquid chromatography using biological samples. The implications of this novel study, pursued by a highly skilled and productive team, will directly advance the current state of the science by expanding on the role of a known pharmacotherapy within this highly vulnerable population. Further, should our central hypothesis be supported, the dissemination of this intervention is clinically applicable, relevant and maybe immediately pursued.