Palma De Mallorca, Islas Baleares, Spain

Functional Incremental Stepping in Place Test (F-IST) Validation

Acutely hospitalized patients are at risk for hospital-acquired functional decline (HAD). This decline increases the likelihood of developing physical disability after discharge, particularly in those with older age, multimorbidity, pre-existing functional impairment and life support exposures (i.e. mechanical ventilation). Identifying patients at increased risk provides important prognostic data to inform planning strategies for both in-hospital and post-acute intervention. Common physiological consequences associated with HAD are diminished skeletal muscle function and cardiorespiratory fitness (CRF). Historically, the six-minute walk test (6MWT) has been utilized as a chief outcome measure in the acute hospitalization and post-discharge phases to examine functional exercise capacity, estimate maximal capacity, and prescribe exercise intervention. The 6MWT is a submaximal field test that allows patients to self-select their walking pace and may be influenced by several factors including motivation. The internally-selected pace coupled with the lack of incremental increases in intensity can underrepresent CRF. In addition, the test requires a 30-meter straight course, which can be challenging to find in the hospital environment. Thus, to address the limitations of submaximal field tests, our team developed the Functional-Incremental Stepping-in-place Test (F-IST). Designed to objectively examine CRF across the variety of patients encountered in clinical practice, the F-IST is an incremental, externally-paced, symptom-limited stepping-in-place test. While maintaining the graded components of gold standard cardiopulmonary exercise testing (CPET), it has high clinical utility since it requires minimal equipment (UE support allowed), minimal space (performed at bedside), and short administration time (< 10 min). Also, the incremental increase in intensity is individualized to perceived exertion and heart rate responses during test stages, which ultimately enables precise exercise prescription. Preliminary data on F-IST from the ongoing randomized controlled trial (NCT05218083) demonstrate potential for strong construct validity when compared to 6MWT (n = 9, spearman rho = 0.65, p = 0.05). However, before implementation in clinical practice, a new test requires the study of its measurement properties to assure that its selection is evidence-based. Findings from this study will demonstrate that F-IST is a robust valid and reliable assessment of CRF that can be implemented on the frontline of acute care physical therapy. The F-IST addresses important limitations of field tests with an enhanced rigor by maintaining principles of gold-standard CPET. The F-IST will enable clinicians and researchers to provide precision exercise prescription to optimize patient function.

Energy Needs and Nutritional Status of Adolescent Girls

Adolescents in low and middle-income countries encounter numerous nutritional challenges, including undernutrition, micronutrient deficiencies, poor dietary habits, and food insecurity. These issues significantly impact their growth, development, and long-term health. Despite their increased vulnerability, this demographic is often overlooked in nutritional program planning and implementation. This neglect is due to a lack of accurate data, inadequate delivery platforms for interventions, and underdeveloped policies and programs. The Nutrition and Adolescence in Rural Nigeria (NARN'ia) study aims to address this gap through a comprehensive assessment of energy requirements in adolescent girls (N=50; ages 10 - 19 years) in Nigeria. NARN'ia will integrate dietary assessments using the 24-hour recall method (INDDEX24 app); physical activity levels using accelerometry; anthropometric evaluations of body composition, and the doubly labeled water method for assessing both body composition and total daily energy expenditure. This study will provide evidence-based data essential for formulating appropriate nutritional guidelines for adolescent girls in Nigeria. Furthermore, this research initiative will establish a foundational framework for future studies on energy requirements in Nigeria and other low and middle-income countries.

Pulmonary Artery DenerVation Clinical Study Using the Gradient Denervation System in Heart Failure Patients With Pulmonary Hypertension Group 2 (PreVail-PH2 Study)

Gradient has developed a novel system for pulmonary artery denervation (PADN) to treat patients with heart failure who also developed pulmonary hypertension (PH). Pulmonary hypertension is frequently associated with left heart failure and is a strong independent predictor of clinical worsening and higher mortality. No therapeutic options are available to treat PH in this selected group of patients with heart failure. The objective is to improve exercise capacity and quality of life by targeting PH in these patients.

Study of Olutasidenib and Temozolomide in HGG

This is a multicenter, international, phase II study of post-radiotherapy (RT) administration of olutasidenib to treat pediatric and young adult patients newly diagnosed with an IDH1-mutant HGG. The trial will include a feasibility cohort to identify the dose of olutasidenib that is feasible when given in combination with temozolomide as maintenance therapy after completion of focal radiotherapy in this patient population. Efficacy will be defined by progression-free survival (PFS) distribution of these patients after completion of radiotherapy treated with maintenance olutasidenib and TMZ for 13 cycles followed by 13 cycles of single agent olutasidenib compared to molecularly-stratified and matched historical controls. Objective radiographic response rates, agent-specific toxicities as well as the pharmacokinetic and pharmacodynamic properties of olutasidenib will also be assessed.

Global Study of Del-desiran for the Treatment of DM1

The study consists of a Screening Period of up to 6 weeks and 54-week Treatment Period. The anticipated duration is approximately 60 weeks. Participants will be randomized to receive an intravenous infusion of either del-desiran or placebo at the clinical study site every 8 weeks for a total of 7 doses. The final dose will occur at Week 48, followed by a final assessment at Week 54. After completion of Week 54 assessments, eligible participants will have the option to enroll into an open label extension (OLE) study, pending regulatory approval. An Independent Data Monitoring Committee (IDMC) comprised of members independent and external to the Sponsor will review safety, tolerability, and efficacy (as needed) data of this study at regular intervals.

ABC-CT Pre-School Feasibility Study

The ABC-CT Pre-School Feasibility Study will collect data in a cohort of participants to determine feasibility of the measures used in the ABC-CT Phase 1 study and ABC-CT Confirmation study in 3-5 year old participants. We will be able to examine distributional and psychometric properties of the measures in this group and obtain preliminary estimates of group differences and associations with clinical measures. In addition, we aim to determine the viability of EEG and ET measures as potential biomarkers in 3-5-year-old children with ASD. Viability will be evaluated in terms of (a) valid data acquisition, including adequate levels of participant compliance, (b) reliability of data collection across sites, (c) construct validity in relation to social function, and (d) distributional/psychometric properties. Primary Objectives: 1. To evaluate the feasibility of collecting EEG and ET assessments used in the Phase 1 and Confirmation studies in 3-5 year old. 2. To determine the viability of adapted EEG and ET measures as potential biomarkers in 3-5-year-old children with ASD and TD. To further evaluate the psychometric properties of the ET and EEG biomarkers in the 3-5 year old population. Secondary Objectives: - To collect blood samples from all ASD subjects and their biological parents for future genomic analyses and to share raw, processed, and analyzed data via the National Database for Autism Research (NDAR) and National Institute of Health / National Institute of Mental Health (NIH/NIMH) Data Repositories to create a community resource accessible for use by all qualified investigators. - To compare estimates of key distributional parameters across the original, confirmation and feasibility samples to determine whether the markers profiles are sufficiently compatible to use in studies combining pre-school and school-aged children. The Preschool Feasibility sample will be evenly divided (25 ASD, 25 TD), aged 3-5, with IQ ranging from 60-150, recruited from 5 clinical implementation sites in the US. Endpoints: To collect and analyze a new cohort of participants to evaluate the feasibility of ET and EEG acquisition in 3-5 year olds. We will also evaluate ET and EEG measures for potential utility as biomarkers in clinical trials. Primary endpoints include evaluation of (1) Acquisition, (2) Construct Validity, (3) Discriminant Validity. Primary Biomarker Outcome Variables. 1. N170 Latency to Upright Human Faces: The N170 Latency to Upright Human Faces (N170 latency) is a scalp recorded EEG event-related potential (ERP) component elicited by perception of the upright human face. Recorded over the posterior-temporal right hemisphere, the latency (or speed) of the peak of the N170 ERP component occurs at approximately 200 msec in children aged 3 to 5 years of age. 2. Oculomotor Index of Gaze to Human Faces (OMI): Onscreen gaze position data, reflected in percentage of foveation (angling of the eyes to focus on a particular object) to human faces (Face%) relative to total valid foveation time across three assays.

Study of Single Doses of SBT777101 in Subjects With Hidradenitis Suppurativa

The study evaluates the safety and effects of a novel regulatory CARTreg cell-based autoimmune and inflammatory disease therapy for the treatment of hidradenitis suppurativa. The therapy is an autologous (using the patient's own cells) Treg cell therapy that targets proteins in the inflamed, disease-associated tissue, with the aim to dampen inflammation and restore balance to the immune system.

Lemborexant Treatment of Insomnia Linked to Epilepsy

Androgens and NAFLD Longitudinal Cohort Study

The studies central hypothesis is that androgens promote liver injury and NAFLD/NASH progression in PCOS, which occurs through aberrant lipid activity (including lipotoxicity and dysregulated de novo lipogenesis), in part from androgenic effects on visceral adipose tissue (VAT). Data in young women taking exogenous testosterone show redistribution of fat from subcutaneous to visceral stores In the general population, VAT promotes NASH through several established pathways, including production of tissue injurious or "lipotoxic" lipids such as some phospholipid, sphingomyelin, and ceramide species. Recent data show androgen- associated increase in serum glycerophospholipids in women with PCOS, a lipid class that is associated with NASH in women. Additionally, androgen-associated de novo lipogenesis (DNL) may contribute to NASH in women. Hepatic DNL is a key source of lipid accumulation, and co-investigators at Duke University recently discovered an enzymatic balance that regulates hepatic DNL with dysregulation of this pathway (reflected by branched-chain keto and amino acids) predictive of prevalent NASH in humans. Androgen-induced de novo lipogenesis also occurs in cultured hepatocytes from women (but not men) supporting the researchers focused evaluation of the relationship between androgens, dysregulated hepatic DNL, and NASH in PCOS. As existing data support androgenic effects on hepatic and visceral fat in women, the researchers will now determine the relationship of androgens with liver injury and progression in PCOS and the potential mechanistic contributions of VAT and aberrant lipid metabolism to this process. The team includes clinical and translational researchers at two centers (UCSF and Duke) with expertise in NAFLD, PCOS, obesity, and lipid metabolism, with a track record of collaboration. The study team will leverage an existing well-characterized PCOS cohort29 to follow 150 reproductive-aged women with NASH (125 PCOS and 25 non-PCOS controls) to accomplish this.

Sling vs No Sling After Reverse Total Shoulder Arthroplasty

The purpose of this study is to determine whether or not a sling is necessary after the nerve block has worn off postoperatively for patients undergoing reverse total shoulder arthroplasty. Patients who are scheduled for a reverse total shoulder with the participating investigators will be approached for potential participation in the study. Before the surgery, subjects will be randomly assigned to either the Sling (control) group or the No-Sling (investigational) group. The Sling, or control, group will wear a sling through 3 weeks postoperatively. The No Sling (investigational) group, will wear a sling either through 3 days postoperatively. Following surgery, patients will be followed at their standard of care visits at 2 weeks, 6 weeks, 3 months, 6 months, 1 year, and 2 years after their surgical date. The investigators will collect data from these standard of care visits including PROs (including but not limited to ASES and SANE), Adverse events data, and physical exam data including range of motion. Patients will be followed through their two-year visit and then taken off study.