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NCT ID: NCT03853746 Active, not recruiting - Multiple Sclerosis Clinical Trials

Short-term B-cell Depletion in Relapsing Multiple Sclerosis

Start date: April 1, 2019
Phase: Phase 4
Study type: Interventional

Several disease-modifying therapies (DMTs) have been shown to be effective in reducing the disease activity in patients with relapsing forms of multiple sclerosis (MS) but these treatments, often need to be used continuously for an unknown duration, rendering the long-term use extremely expensive. In addition, chronic administration of DMTs is often associated with undesirable side effects. Among these medications, B-cell depleting monoclonal antibodies might have the properties of an ideal group of medications: i) B-cell depleting antibodies have proven to be extremely potent in reducing or stopping the disease activity in relapsing MS, ii) B-cell depleting antibodies are very safe if used for a short period and use for a short duration may stop the inflammatory disease activity over long term, although current clinical practice and protocols are based on continuing B-cell depletion for an unknown period of time. Indeed, early phase clinical trials of rituximab and ocrelizumab suggested that a short course treatment with B-cell depleting antibodies can have long term effects and disease activity will not return even long after B-cell repopulation in the blood. This long-term effect might be related to the specific pattern of B-cell tolerance defect in patients with MS and the potential of its normalization with B-cell depleting antibodies. By analyzing the reactivity of recombinant antibodies expressed from single B-cells, the investigators' collaborators have demonstrated that the pattern of B-cell tolerance defect is different in people with MS who only display an impaired removal of developing autoreactive B-cells in the periphery while central B-cell tolerance in the bone marrow is functional in most patients. In contrast, patients with rheumatoid arthritis (RA), type-1 diabetes (T1D) or Sjögren's syndrome (SS) show defective central and peripheral B-cell tolerance checkpoints. As a consequence, while anti-B-cell therapy does not correct defective early B-cell tolerance checkpoints in T1D and only temporarily slows down autoimmune processes before newly generated autoreactive B-cells likely induce patient relapse, the investigators postulate that the efficacy of B-cell depleting antibodies in MS may be linked to the B-cell depleting antibodies' normal central B-cell tolerance and the production of a normal B-cell and T-cell compartment after anti-B-cell therapy. The investigators' goal is to provide proof-of-concept that a short duration of treatment with B-cell depleting antibodies can correct B-cell tolerance defects in MS and allow for medication-free prolonged freedom from disease activity, at least in a proportion of subjects with relapsing MS. In an open label study, 10 patients with active relapsing MS will be treated with two courses of ocrelizumab and will be followed clinically and radiologically for at least two and a half years. Time to the return of disease activity (defined as clinical relapses or new or enhancing lesions on the MRI) will be the primary outcome of the study. The investigators will harvest B-cells before starting the treatment and after B-cell repopulation and assess the central and peripheral tolerance defects. The investigators hypothesize that in most participants, the disease activity will not come back, and this prolonged response to anti cluster of differentiation 20 (CD-20) therapy is associated with normalization of B-cell tolerance defect in these patients. Considering the safety of this approach, it can be adopted widely among people with MS. Hence, the proposed B-cell analyses before and after B-cell depletion in people with MS will provide novel insights regarding the mechanisms underlying the beneficial effect of B-cell depleting antibodies and the potential long-term suppression of disease activity. This strategy can therefore improve the approach to treatment of many people with relapsing MS.

NCT ID: NCT03854903 Active, not recruiting - Clinical trials for Metastatic Breast Cancer

WI231696: Bosutinib, Palbocicilib and Fulvestrant for HR+HER2- Advanced Breast Cancer Refractory to a CDK4/6 Inhibitor

Start date: April 1, 2019
Phase: Phase 1
Study type: Interventional

This is an open-label, single-arm, phase I trial. It is designed with a conservative dose escalation plan to ensure patient's safety and with a strong translational component to inform if target inhibition is achieved. With concerns regarding safety, based on extensive available pharmacokinetic data and clinical efficacy experience, bosutinib will be given 5-days in a row followed by 2 days rest in a weekly basis, instead of daily. The protocol will enroll patients per 3+3 escalation design. The Dose Limiting Toxicity (DLT) observation period is 28 days. At the end of DLT observation period of each cohort of 3 patients, decision will be made regarding further escalation or de-escalation according to this plan. Once the MTD of the combination is reached, the safety data will be analyzed. There will be no dose reductions during DLT observation period. Dose reduction within patients (individually) is allowed after the 4-week DLT observation period. Treatment in this phase I trial will be administered until there is disease progression or unacceptable toxicity.

NCT ID: NCT03860168 Active, not recruiting - Critical Illness Clinical Trials

PICU Up!: A Pilot Stepped-wedge Trial of a Multicomponent Early Mobility Intervention for Critically Ill Children

PICU Up!
Start date: April 1, 2019
Phase: N/A
Study type: Interventional

Recent decreases in Pediatric Intensive Care Unit (PICU) mortality rates have been offset by increased morbidity and length of stay for vulnerable young patients. Heavy sedation, bedrest, and delirium contribute to a PICU culture of immobility. While studies in adult ICU patients demonstrate the clinical benefits of early mobilization, fewer than 25% of critically ill children mobilize early in the children's PICU stay. The investigators have demonstrated the safety and feasibility of the 'PICU Up!' Mobility Program, which integrates sleep promotion, delirium prevention, sedation optimization as a bundle to increase mobilization. However, the generalizability and broader impact on patient- and family-centered outcomes is unknown. Therefore, there is an urgent need for trials that blend both clinical effectiveness and implementation research to create a PICU culture of mobility and improve the value of PICU care. The overall objective of the proposed research is to determine the impact of a transdisciplinary and multifaceted early mobility program on clinical outcomes and ICU-acquired morbidities in critically ill children. Additionally, the investigators will identify barriers and facilitators to high-performance bundle adoption.

NCT ID: NCT03861533 Active, not recruiting - Dyslipidemia Clinical Trials

GOAL International QuERI - Protocol CHRC 2019 GOAL INTERNATIONAL

GOAL QuERI
Start date: April 1, 2019
Phase:
Study type: Observational [Patient Registry]

This Quality Enhancement Research Initiative (QuERI) is a knowledge translation medical practice activity based on decision making support through feedback to physicians on their management of dyslipidemia in order to achieve guidelines recommended LDL-C levels in high risk patients. Physician interaction has three distinct components: 1. Capture of data as reported by participating physician; 2. Highlight (by providing feedback) where management may be optimized based on guidelines or recommendations; 3. Identify challenges faced by physicians resulting in the care gap..

NCT ID: NCT03871712 Active, not recruiting - Clinical trials for Musculoskeletal Pain

Effectiveness of Motivational Interviewing on Return to Work in People on Sick Leave Due to Musculoskeletal Disorders

MI-NAV
Start date: April 1, 2019
Phase: N/A
Study type: Interventional

Musculoskeletal disorders are the main causes for sickness absence and disability benefits in Norway and the leading causes of disability worldwide. There is strong evidence that long-term sickness absence due to musculoskeletal disorders provides a poor prognosis, both in terms of work-related disability, physical and mental health, and health related quality-of-life. To assist people return to work a range of vocational rehabilitation programs exist, but the initiatives have not been able to reduce the number of people who are on sick leave due to musculoskeletal disorders. In Norway, The Norwegian Labour and Welfare Administration (NAV) case-workers have taken such approaches in use, primarily by teaching their employees with user contact in how to use Motivational Interviewing (MI). However, the evidence on the effectiveness of MI on return to work is highly uncertain. The objectives of this project are to compare the effectiveness and cost-effectiveness of usual case management alone with usual case management plus MI or usual case management plus stratified vocational advice intervention (SVAI), on RTW among people on sick leave due to musculoskeletal (MSK) disorders. All musculoskeletal diagnoses will be included. A multi-arm randomised controlled trial with 150 participants in each group will be conducted within the NAV system in Norway to evaluate these research questions.

NCT ID: NCT03880435 Active, not recruiting - Infertility Clinical Trials

HYALOBARRIER® GEL ENDO Versus no HYALOBARRIER® GEL ENDO Following Operative Hysteroscopy for Improving Reproductive Outcome in Women With Intrauterine Pathology Wishing to Become Pregnant

AGNOHSTIC
Start date: April 1, 2019
Phase: N/A
Study type: Interventional

To compare the costs and effects of HYALOBARRIER® GEL ENDO versus no HYALOBARRIER® GEL ENDO for increasing the chance of conception leading to live birth measured at 30 weeks after randomization in women wishing to become pregnant after surgical removal of intrauterine pathology (endometrial polyps, fibroids with uterine cavity deformation, uterine septa, IUAs or RPOC after miscarriage) by hysteroscopy as an outpatient or in hospital treatment.

NCT ID: NCT03892226 Active, not recruiting - Stroke, Ischemic Clinical Trials

Cardiomyocyte Injury Following Acute Ischemic Stroke

CORONA-IS
Start date: April 1, 2019
Phase:
Study type: Observational

The primary goal of the CORONA-IS study is to characterize stroke-associated acute myocardial injury (elevated hs-cardiac troponin) using different diagnostic examinations in order get a better understanding of it's underlying pathomechanisms.

NCT ID: NCT03893396 Active, not recruiting - Clinical trials for Angiospastic; Disorder

Safety Assessment of Angioplasty Procedures

SCRAP
Start date: April 1, 2019
Phase:
Study type: Observational [Patient Registry]

Ischemic heart disease, or coronary heart disease, covers a set of pathologies due to insufficient oxygen supply to the myocardium due to the development of atherosclerosis in one or more coronary arteries. To evaluate the safety of angioplasty performed in patients operated on at La Rochelle Hospital, the rate of major adverse cardiac events (MACE) will be determined and compared with data from the literature.

NCT ID: NCT03894566 Active, not recruiting - Mental Disorders Clinical Trials

NASCITA Italian Birth Cohort Study

NASCITA
Start date: April 1, 2019
Phase:
Study type: Observational

The NASCITA study (NAscere e creSCere in ITAlia) was created to improve the understanding of the health status of Italian children early on and how it is affected by social and health determinants. The study will evaluate physical, cognitive, and psychological development, and health status and health resource use during the first six years of life in a group of newborns, as well as potential associated factors. The association between the well-being of children and parental adherence to the recommendations for better child care and development will also be assessed. Information on the children will be collected by paediatricians mostly during routine visits. The findings will be used in the development of specific prevention measures and interventions to improve the health of children, in particular more vulnerable ones.

NCT ID: NCT03897036 Active, not recruiting - Clinical trials for Carcinoma, Basal Cell

Treatment Duration Increment and Pharmacodynamic Study of CX-4945 in Patients With Basal Cell Carcinoma (BCC)

Start date: April 1, 2019
Phase: Phase 1
Study type: Interventional

This study is to determine the recommended phase II dose (RP2D) and schedule of CX-4945 when administered orally twice daily for 28 consecutive days, in a 4-week (28 days) cycle, in patients with locally advanced or metastatic basal cell carcinoma (BCC). The safety and tolerability of CX-4945, preliminary evidence of antitumor effect, and the effect of CX-4945 treatment on the Hh signaling pathway will also be evaluated in this study.