One Or Multiple Investigational Sites, Spain

Transform CV Risk in Diabetes

Filgrastim-Mobilized Stem Cells for Transplantation Using Unrelated Donors

For many years, allogeneic bone marrow transplantation has been used to successfully treat leukemias, other hematologic conditions and congenital disorders. The first unrelated donor transplants were performed in the late 1970s, but this procedure did not become widely available until the development of several consolidated unrelated donor registries around the world. The National Marrow Donor Program, established in 1987, is the world's largest registry and currently lists more than 7 million donors. Since its beginning, NMDP has facilitated more than 30,000 unrelated transplants. Although not a licensed indication, considerable experience has been accumulated concerning administration of filgrastim to normal adults. Most of these adults were volunteer research subjects or donors of PBSC for use in related donor transplants. Beginning in February 1997, filgrastim stimulated PBSC have been collected from NMDP donors under protocol. The protocol (locally referred to as G2) began under an NMDP-sponsored Investigational New Drug (IND) application filed with FDA for collecting PBSC for a second donation following an initial donation of bone marrow. In 1999 a second protocol was opened (locally referred to as G1) as requests for PBSC as a primary donation source became more common. In 2005 the two protocols were combined to eliminate redundancy and provide for ease of use. The protocol establishes and evaluates a system to supply peripheral blood stem cell (PBSC) products for use in unrelated donor hematopoietic stem cell (HSC) transplantation. The protocol describes processes for donor identification, education and evaluation. Procedures for administration and monitoring of the stem cell mobilizing agent filgrastim are included. The protocol also describes procedures for the collection of PBSC products by leukapheresis and includes provisions for long term donor follow-up.

SPR PNS for Chronic Shoulder Pain

Background Chronic degenerative changes in the shoulder are a frequent source of debilitating chronic pain. In particular, osteoarthritis of the shoulder has been estimated to affect up to 32.8% of the adult population over the age of 60, and OA in general is one of the most frequent causes of disability in the United States.1 OA impacts the quality of life of tens of millions of Americans and carries a significant economic burden of over $60 billion in the U.S. each year.2 Degenerative joint disease in the shoulder is commonly managed with physical therapy and over-the-counter medications, but these modalities can be insufficient for pain management as degeneration progresses.3 Corticosteroid injections, radiofrequency ablations, and even partial or total shoulder arthroplasty are used to treat advanced cases3, and these interventions often either have limited long-term effectiveness or are associated with significant invasiveness or other side effects and complications. Peripheral nerve stimulation (PNS) is a neuromodulatory technique that seeks to provide pain relief through stimulation of the nerves that innervate the shoulder (e.g., the suprascapular nerve and axillary nerve). A novel, 60-day percutaneous PNS system that is FDA-cleared has shown effectiveness for chronic shoulder pain following stroke and shoulder impingement syndrome4-15, and has demonstrated the potential to provide sustained relief following the short-term, 60-day treatment.8, 15-18 The mechanism of action of neuropathic pain in osteoarthritis is proposed to be via peripheral sensitization (e.g., axillary and suprascapular nerves) that leads to subsequent upstream hypersensitization of the central nervous system; the proposed mechanism of long-term pain relief with 60-day PNS via reconditioning of the CNS to reverse hypersensitization therefore suggests that the treatment may be effective for degenerative shoulder including OA.19, 20 However, no study has prospectively evaluated the use of 60-day, percutaneous PNS for the treatment of debilitating pain associated with degenerative changes in the shoulder. The goal of this study is therefore to collect data on the use of 60-day PNS for the treatment of chronic pain associated with degenerative shoulder. Objectives The study objective is to gather post-market data regarding the effectiveness of the SPRINT PNS System for the treatment of chronic shoulder pain due to degenerative changes of the shoulder.

A Phase 2b/3a Study to Evaluate the Efficacy and Safety of JointStem in Patients Diagnosed as Knee Osteoarthritis

Study Procedures: - Visit 1 (Week -7) - Screening - Visit 2 (Week -5) - Baseline and Randomization (Lipoaspiration) - Visit 3 (Week 0) - Treatment (Intra-articular injection) - Visit 4 (Week 4) - 4 weeks follow-up - Visit 5 (Week 12) - 12 weeks follow-up - Visit 6 (Week 24) - 24 weeks follow-up - Visit 7 (Week 36) - 36 weeks follow-up - Visit 8 (Week 48) - 48 weeks follow-up (End of Study)

Dose of Vestibular Rehabilitation for Vestibular Hypofunction

Disorders of vestibular function are prevalent disorders that result in dizziness, decreased balance, and a 12-fold increased risk of falls.1 It has been determined that 20% of community-dwelling adults over the age of 60 report vestibular symptoms prompting a medical evaluation or intervention over a one year period.2 This equates to approximately $50.0 billion in annual healthcare costs.3 In the US alone, there are approximately 1.6-3.8 million sport concussions each year,4,5 where 50% of concussed athletes have at least one vestibular type symptom.6 Although the impact of cost has been demonstrated in older adults, the costs of concussion-related dizziness is much more difficult to calculate due simultaneously treating symptoms from multiple systems. A common treatment for symptoms related to disorders of vestibular function is vestibular rehabilitation, a sub-specialty of physical therapy. These exercises are performed daily by Subjects at home and consist of visually fixating on a target while moving the head and/or the object on which the subject is fixating. To alter exercise difficulty, exercise parameters are altered including: visual background complexity (plain and dark, busy but stationary, moving objects, rapidly moving objects), postural positioning (seated, standing with a wide base of support, standing with a narrow base of support, standing on one leg), and duration of exercise (from 5 seconds to approximately 2 minutes). Early evidence shows that vestibular rehabilitation exercises provided by a physical therapist is an effective method of ameliorating vestibular hypofunction. Further, effectiveness of vestibular rehabilitation does not decline with increasing age of the patient,8 indicating benefit for all ages that are affected. Unfortunately, many factors limit the ability to determine efficiency and efficacy of treatment and have been highlighted in a recent clinical practice guideline9 and systematic review5,10. Limitations include: poor measurement of prescribed exercise compliance by depending on subjective report, inability to control for environmental factors during home program execution, and the influence of noxious vestibular input associated with traveling to attend scheduled physical therapy visits. These factors hinder performing high quality efficacy studies, resulting in exercise prescription being largely based on expert opinion, the lowest level on the hierarchy of evidence-based practice.11 In fact, current opinion indicates that exercises should be performed 3 times a day for a total of 12 minutes with each bout lasting approximately 2 minutes, all with no clear indication of speed and amplitude of performance. In this study, the investigators aim to use a commercially available virtual reality device to deliver usual vestibular rehabilitation exercises, while using the device's inbuilt sensors to accurately measure head movement, speed and duration. Using this device, the investigators will assess compliance and dose of exercises required to reduce symptoms of dizziness and imbalance and to determine if performing such exercises in a virtual reality environment will provide similar results to that usual rehabilitation techniques. When a potential subject is identified, the subject will be screened for appropriateness of inclusion for this study. After informed consent has been obtained from a recruited subject, those with Unilateral Vestibular Hypofunction (UVH) will be asked to perform a 4-week intervention, while those with Bilateral Vestibular Hypofunction (BVH) or those post-concussion will each be asked to perform a 12-week intervention. Those with UVH will undergo a shorter intervention due to strong evidence that neural adaptation occurs much more quickly (usually 4 weeks) than those with BVH and history of concussion.9,10,17-19 The intervention will consist of physical therapy visits combined with a home program of specific vestibular exercises. Each subject will be asked to attend physical therapy visits at least one time per week throughout the 4- or 12-week period. Assessments will be performed on all groups and consist of a combination of vestibulo-ocular assessment, balance and clinical functional outcome measures, and surveys of subject satisfaction. Subjects are randomly assigned to the usual rehabilitation or intervention group based on each of the following diagnostic categories. The compliance to exercises will be obtained from a log in the virtual reality device for the VR group, and will be paper based for the usual physical therapy group. Subjects in the three intervention groups will be asked to perform the same type of exercises as the usual rehabilitation group, but using a virtual reality device that will be issued to the patient for home use. Subjects will use a custom designed program to perform the exercises using a commercially available virtual reality device (no specialized hardware or additions to the commercially available device will be performed). Subjects will be instructed on the first day in how to operate the Virtual Reality Vestibular Rehabilitation (VRVR) program and how to properly perform the exercises. The VRVR device and software will simulate a virtual reality 'room' with an 'X' fixed in front of a wall. There are six different background complexities. Exercise sessions will start seated upright in a chair and will progress to standing per the home exercise protocol. The system will prompt the patient to begin the exercise and will automatically log the frequency and duration of exercise performed. The system will ask the patient to rate the severity of their symptoms on a 0-10 scale before and after each bout of exercise. Subjects' instruction regarding initial dose and progression will be identical to those given in the usual rehabilitation group. Subjects will be asked to bring their device with them to their 4 week, 8 week, and 12 weeks appointment to transfer their de-identified data and to insure integrity of the data and device. Subjects will be asked to return the device at the end of the intervention period. Per patient and therapist discretion, additional physical therapy visits may be scheduled to aid in patient understanding of exercise progression protocol, assess correct performance of exercise (with or without virtual reality device). Non-study related physical therapy visits may be scheduled between sessions in order to address impairments unrelated to vestibulo-ocular deficits. These may include interventions to address musculoskeletal deficits or other balance related impairments. Any additional sessions of physical therapy will be reported in order to determine possible confounding information. There will be an additional group of healthy control subjects that will be tested for only one day. Healthy subjects will be recruited through flyers, approved email lists, and word of mouth in the general public. This healthy control group will perform the same tests as the other groups perform on Day 1. This group will be used to compare outcomes of usual rehabilitation and intervention groups, to the function of those without disorders of vestibular function.

ZILRETTA in Subjects With Shoulder Osteoarthritis

This is a multi-center, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of ZILRETTA in subjects with glenohumeral OA. This study will be conducted at approximately 25 study sites in the United States. Subjects will be screened to confirm the diagnosis of OA and eligibility based on the Inclusion and Exclusion Criteria. Approximately 250 male or female subjects, 50 to 80 years of age inclusive, will be enrolled, randomized to 1 of 3 treatment groups (2:2:1), and treated with a single IA injection of either: - Treatment Arm 1: 32 mg ZILRETTA, - Treatment Arm 2: 40 mg Immediate Release Triamcinolone (TCA-IR), or - Treatment Arm 3: placebo (normal saline). ZILRETTA, TCA-IR, or normal saline placebo will be administered as a single IA injection with a 24-week follow-up period with a primary endpoint at Week 12. The study will involve a Screening period (a minimum of 10 days, up to a maximum of 35 days), pre-treatment phase, dosing at Baseline/Day 1, and 8 additional outpatient visits at Weeks 2, 4, 8, 12, 16, 18, 20, and 24/End of Study (EOS) during the study. At specified times throughout the study, subjects will undergo physical examinations, index shoulder assessments, and index shoulder X-rays; blood will be collected for laboratory safety tests; and vital signs will be collected. Information regarding adverse events (AEs) and prior and concomitant medications and treatments will be collected from the time of signing the Informed Consent Form (ICF) through the Week 24/EOS visit. Information regarding rescue medication usage, Average and Worst daily Pain score (0-10 Numeric Rating Scale (NRS); 0 = no pain, 10 = worst possible pain) in the index shoulder, and Sleep Interference (SI) will be completed daily via an electronic diary (eDiary) and reviewed for compliance by site staff at each study visit. At the Screening Visit, subjects will be registered in the eDiary and receive instructions on its use. Subjects will complete accurate pain reporting (APR) and placebo response reduction (PRR) training prior to completing all questionnaires.

Intervention to Enhance PrEP Persistence

Black/African American (B/AA) gay, bisexual, and other men who have sex with men (MSM) are at high risk for HIV acquisition in the United States (US). Although B/AA MSM account for less than 1% of the US population, they comprise 26% of new HIV infections. An estimated 41% of B/AA MSM acquire HIV during their lifetimes. HIV pre-exposure prophylaxis (PrEP) can dramatically reduce HIV incidence for B/AA MSM. B/AA MSM have poorer outcomes at every stage of the PrEP care continuum. B/AA MSM are less likely to initiate PrEP, and be retained in care than non-Hispanic White MSM. PrEP care outcomes among B/AA MSM are influenced by complex social and structural factors, such as difficulty accessing culturally congruent healthcare services, insufficient health insurance, high out-of-pocket costs, and stigma associated with PrEP, sexual orientation, and HIV. The US Ending the HIV Epidemic (EtHE) initiative and the National HIV/AIDS Strategy call for expanding PrEP to B/AA MSM at community health centers (CHCs), but few interventions exist to overcome barriers and improve PrEP care outcomes in this setting. Moreover, access to PrEP navigation services in real-world settings is uneven. While some clinics offer PrEP navigation services, there is no standard or scientific consensus about how to enhance PrEP adherence and retention in care for B/AA MSM. There is also a lack of data on the degree of intensity and time for navigation services to achieve optimal PrEP outcomes for this population. The investigator's NIH-funded pilot randomized controlled trial (RCT) (R34MH109371; MPI: Nunn, Chan, Mena) developed and evaluated the Retain and Adhere MSM on PrEP Intervention (RAMP-IT-UP), a strengths-based patient navigation program to enhance PrEP care outcomes among B/AA MSM at a CHC in Jackson, Mississippi. RAMP-IT-UP included one 60-minute personalized patient navigation session, bidirectional communication, scheduled short (10-minute) phone check-ins with navigators, tailored strengths-based strategies to overcome barriers, optional tailored daily medication reminders via text message, and transportation assistance as needed. RAMP-IT-UP also included monthly calls to patients' pharmacies to assess prescription pick-ups, allowing the navigator to connect with patients in a timely manner to understand why a PrEP prescription was not filled. RAMP-IT-UP provides real-time support to overcome social, structural and clinical barriers to PrEP initiation, retention, and adherence and was highly acceptable among B/AA MSM. Compared to control participants, RAMP-It-Up participants were much more likely to initiate PrEP (93% vs. 63%, p=0.01) and to adhere to PrEP based on pharmacy fill data (70% vs. 23%, p<0.01) and 3-month drug levels (83% vs. 50%, p=0.20). Additionally, RAMP-It-Up participants were more likely to be retained in PrEP care at 3-month (70% vs. 43%, p=0.05) and 6-month (37% vs. 27%, p=0.42) PrEP visits. The objectives of the proposed study are to conduct a fully multi-site RCT to determine the effectiveness and cost-effectiveness of RAMP-It-Up for improving PrEP care outcomes among B/AA MSM in real-world CHC settings. The long-term goal of this work is to decrease HIV incidence among B/AA MSM, which aligns with EtHE and National HIV/AIDS Strategy goals. The investigators propose the following specific aims: Specific Aim #1: Conduct a fully powered RCT to estimate the effectiveness of RAMP-It-Up among B/AA MSM attending CHCs. The investigators will enroll n=300 B/AA MSM who intend to initiate daily oral PrEP at CHCs in three US urban centers (N=100 each site): Jackson, Mississippi; Washington, District of Columbia; and Providence, Rhode Island. Block randomization will be used to randomize participants at each site to either RAMP-IT-UP or an attention-matched information/referral control condition (enhanced treatment-as usual [ETAU]). Quantitative research assessments will be conducted at baseline and 3-, 6-, 9-, and 12-months post-baseline. The primary outcome will be PrEP adherence, given that adherence is the definitive marker associated with protection from HIV infection. The investigators will measure adherence with pharmacy refill data and validate pharmacy refill data with PrEP drug levels. Secondary analyses will evaluate PrEP initiation and retention in care at clinical visits. The investigators hypothesize that, compared to ETAU, RAMP-It-Up will significantly improve PrEP initiation, adherence, and retention in care outcomes. Specific Aim #2: Estimate the cost-effectiveness of RAMP-It-Up among B/AA MSM attending CHCs compared to ETAU. The investigators will employ intervention costing methods to evaluate costs of delivering RAMP-It-Up based on a comprehensive suite of tailored navigation services compared to ETAU. The investigators will then use a Markov state-transition model to estimate the cost-effectiveness of RAMP-It-Up compared to ETAU, in terms of cost-per-person initiating PrEP, adhering to PrEP, and being retained in PrEP care. The investigators will also determine the cost-effectiveness of differing levels of intensity of navigation services to prevent HIV based on data collected in Specific Aim #1. The ultimate goal is to develop a cost-effective intervention that enhances PrEP care outcomes and reduces HIV incidence among B/AA MSM that will be relevant for CHCs. This study is led by a highly successful research team with a long-standing history of collaboration on PrEP implementation studies in real-world settings. This proposal aligns with EtHE and National HIV/AIDS Strategy goals of scaling PrEP in real-world settings in geographic hotspots, with a focus on B/AA MSM.

PositiveLinks: mHealth for DC Cohort

Aim 1: To determine the feasibility, acceptability, and usability of PL, the investigators will conduct mixed methods research among the DC Cohort Executive Committee members (one focus group with a maximum of 20 members), providers from each of the DC Cohort participating clinics (individual in-depth interviews with a maximum of 28 providers), members of the DC Regional Planning Commission on Health and HIV (COHAH; one focus group with a maximum of 50 members), and PLWH who receiving care at each of the DC Cohort participating clinics (four focus groups with a maximum of 8 clinic patients in each group for a total of 32; user testing sessions followed by a survey with a maximum of 14 clinic patients; and beta testing preceded by a short demographic survey and followed by a brief in-depth interview and survey with a maximum of 14 clinic patients). Following user testing, the research and developer teams will review formative results and finalize the optimal set of app features for this urban cohort of PLWH. Following beta testing, the research and developer team will review results and make final app modifications. The prototype will pass stringent testing showing the app to be 100% bug-free, with no data loss. The app has robust transmission retries and data caching on the phone during periods of internet signal loss. Once connection is restored, all cached events are automatically sent to the PL servers on AWS (Amazon Web Services) S3 and are synchronized. The investigators will proceed to beta testing when it passes data reliability testing (retry, cache, re-send) at a 0% failure rate. For the focus group, interview, and user testing participants, consent will be obtained verbally and a waiver of documentation of consent is requested. For beta-testing participants, written informed consent will be obtained. For the EC focus group, COHAH focus group, and provider interviews, participants will be sent a link to a brief REDCap survey prior to the study activities. The surveys will not be linked to their identities. For the focus groups with PLWH, participants will also be sent a link to a brief REDCap survey prior to the focus groups. During the user testing sessions, participants will be asked to download the app onto their phones. Users will be shown various app features by the study team and asked to share their impressions. Following the sessions, testers will be provided a link to the REDCap user testing survey. Users will be assigned a unique survey ID that will be linked to their DC Cohort ID so that they can be compensated. During the beta testing, participants will be asked to attend a virtual training session where participants will download the PositiveLinks app onto their personal smartphone, a study team member will set up the participants' PositiveLinks app account, and a study team member will demonstrate how to access PositiveLinks and its features. Throughout the beta testing period, the study team will continuously collect data paradata or data related to app usage. This includes the frequency with which each participant uses app features as well as in-app data such as content information from check-in entries and comments, reminders, and community message board comments. Data collection will also include a 15-minute virtual user interview to debrief usage, likes and dislikes, identify bugs, and provide recommendations after one month of PL use. Along with an interview, participants will also complete a quick survey that will question participants overall experience with the app. Aim 2: Aim 2 will entail a Cluster Randomized Clinical Trial that randomizes DC Cohort clinic patients (n=482) to either PL (n=6 clinics), or to the usual care conditions for engaging and retaining people in HIV care (n=6 clinics). Participants will be persons living with HIV who are previously enrolled in the DC Cohort or are eligible to enroll in the DC Cohort and have factors that may put them at risk for poor retention in care or lack of viral suppression (e.g. not virally suppressed, not retained in care, gap in care >=6 months, newly diagnosed, etc.). Participants from clinics randomized to PL will get the patient smartphone app; clinic staff will receive the provider portal and provider smartphone app, the provider online LMS (learning management system), and the RA (research associate) will use the administrative website to enroll participants. Patients randomized to PL will use it for 12 months or more; they can opt to use it as long as it is available during the study (access depending on enrollment date). Participants from clinics randomized to Usual Care: Participants from clinics randomized to Usual Care will receive usual clinic retention and medication adherence support services for 12 months . The usual care condition ranges from having no ancillary support to only case management, to Ryan White funding and comprehensive services (adherence support, patient navigation, mental health, substance abuse, dental services and food banks).Participants will be assessed at baseline, 6 months, and 12 months to measure the primary outcomes of a) viral suppression (i.e., VL<200 copies/ml) at 12 months, b) Visit Constancy (i.e., proportion of 4-month time intervals in which 1 HIV care visit was completed in 1 year, and c) Retention in care (i.e., 2 appointments separated by 90 days within 12 months per HRSA-1) Aim 3: The investigators will conduct mixed methods research (in-depth interviews and focus groups) guided by the Consolidated Framework for Implementation Research and RE-AIM to identify site, patient, provider, and system factors that are barriers and facilitators of processes and outcomes of implementation at the 6 sites randomized to PL.

The Duchenne Registry

The Duchenne Registry (previously DuchenneConnect) was created in 2007 by Parent Project Muscular Dystrophy (PPMD), with assistance from the NIH, the CDC, and Emory Genetics. In early 2011, PPMD alone began financing the registry's operation and maintenance, and is the sole guardian of The Duchenne Registry and its material. Questions may be addressed to the Duchenne Registry Coordinators at telephone 888-520-8675 or coordinator@duchenneregistry.org. The Duchenne Registry Coordinators are certified genetic counselors who are available to answer questions regarding the registration process, genetic testing and counseling, and clinical trials and research studies.

Development of a City-Wide Cohort of HIV-Infected Persons in Care in the District of Columbia: the DC Cohort

All major community and academic clinics treating HIV-infected persons in the District of Columbia (DC) will initially be included in the development of a city-wide "DC Cohort" of HIV-infected persons in care, with consideration to be given subsequently to the inclusion of large private physician practices. Socio-demographics, risk factors, treatments, diagnoses, labs and procedures documented in outpatient medical record systems will be included in the DC Cohort database. Routine reports will be generated every six months for sites comparing their participants' socio-demographics, clinical status, treatments, and outcomes to all other data in the DC Cohort database, and other comparisons specifically requested by sites. All sites will be provided analytic support in research areas of interest.