All clinical trials

This study is a randomized Phase 2 trial to determine the feasibility of real-time electrocorticographic monitoring of spreading depolarizations (SD) to guide implementation of a tier-based protocol of intensive care therapies, aimed at SD suppression, for the management of patients who have undergone acute operative treatment of severe traumatic brain injury.

Cognitive behavioral therapy (CBT-I) is a common treatment for insomnia that does not use medications. While CBT-I is effective for insomnia, it does not tend to improve the waking symptom of fatigue. Another treatment, Bright Light Therapy, is used for treating seasonal depression and sleep disorders, and may improve fatigue and physical activity in individuals with PAH. The purpose of this study to assess the effects of Bright Light Therapy compared to CBT-I to treat insomnia and fatigue in patients with PAH.

The investigators are studying a new rehabilitation treatment for individuals trying to recover walking after spinal cord injury (SCI). The investigators will test conditions in the blood and spinal fluid to determine the best time to start this new training program. This will include checking for certain features called biomarkers by testing participants' spinal fluid and blood and compare these features to individuals without SCI. These features will help investigators determine when to start the new training program, either right away or waiting for 3 months. The new training program uses walking downhill on a slight slope on a treadmill while muscles that are not working normally are stimulated to contract using low levels of electricity. Adding this stimulation will allow people to practice walking and other skills even though full muscle control has not recovered. This new program will be in addition to any other rehabilitation therapy and will not replace standard rehabilitation. The hope is to see if downhill training with muscle stimulation, when delivered at the most ideal time, will improve trunk and leg movement, walking, and overall function. This recovery of movement and function will be compared to people with SCI receiving standard rehabilitation alone. Certain regions of the brain and spinal cord will also be studied using MRI scans to determine if these are affected by the training and compare to individuals without SCI. The total length of the study for SCI participants will be up to 16 weeks if in the standard of care group and up to 33 weeks if in the trained group. Healthy control participants will be involved for 1-2 visits.

Primary immune thrombocytopenia (ITP) is an autoimmune disease mainly mediated by autoreactive B cells and the presence of pathogenic anti-platelet auto-antibodies that enhance platelet destruction and impair platelet production. There are approximately 4,000 newly diagnosed ITP cases each year in France. For patients with a platelet count of less than 30x109/L and/or bleeding symptoms, corticosteroids alone or in combination with intravenous immunoglobulin (IVIg) is the standard first-line treatment. However, approximately two-thirds of adult patients responding to this first-line treatment relapse within days or weeks after corticosteroids withdrawal and overall, the course of the disease is chronic in about 70% of the cases. The anti-CD20 monoclonal antibody rituximab is commonly used off-label as a second-line therapy in many European countries including France for adults with persistent (i.e., disease duration of more than 3 months) or chronic (disease duration of more than 12 months) ITP. Rituximab leads to an overall response rate of only 40 % at 1 year but 29.5% of lasting (5 years and more) response The investigators have shown that the absence of response to rituximab in ITP could be explained by the settlement and expansion of long-lived autoreactive plasma cells in the spleen made possible by the high amount of BAFF. Belimumab is a fully humanized anti-BAFF/Blys monoclonal Ab licensed for SLE. Based on the preliminary results of a phase 2 open prospective pilot study performed in our center combining rituximab with i.v belimumab seems highly promising We hypothesized that combining subcutaneous belimumab weekly over a 24 weeks period (Arm A) with rituximab is superior to rituximab and subcutaneous placebo weekly over 24 weeks period (Arm B) to achieve an overall response at W52. The study design will be a prospective randomized, double-blind, multicenter (international), superiority phase III clinical study

Background: Loneliness-a subjective emotional state characterized by the perception of social isolation-is a psychosocial factor that is associated with increased mortality, substance use, and is associated with precipitants of relapse among individuals with substance use disorders (SUD). Importantly, there are effective interventions that can be used to decrease loneliness; however, these have not been tested on Veterans with SUD who are lonely. Significance/Impact: Individuals with SUD have higher prevalence of loneliness and loneliness exacerbates pain and sleep disturbance, risk factors of relapse. Without effectively intervening on loneliness, Veterans with SUD will continue to be at high risk of relapse and will maintain problems engaging with social support, including healthcare providers-factors critical for recovery. Cognitive-behavioral therapies (CBT) has shown the strongest effects on loneliness, however, there are no interventions that are specifically designed for substance using populations who are lonely. Testing CBT for loneliness and SUD (CBT-L/SUD) has the potential to have a broad impact on addressing a critical, unmet need that commonly affects Veterans with SUD. The investigators approach of national recruitment and telehealth delivery of this intervention highlights how this this study address VHA care priorities including substance use, access to care, and telehealth. Innovation: There are no studies that have tested a loneliness intervention in Veterans with SUD who are lonely, which may neglect a broader impact on mental and physical health. This study is ideally situated to generate new and important knowledge on the association of loneliness and SUD. This study seeks to address a transdiagnostic factor, which may improve engagement with social support thereby reducing substance use. An additional innovative aspect of this study is recruitment being conducted outside the VHA. This may increase access to care among those Veterans who are especially isolated. Specific Aims: the investigators aim to: (1) refine the CBT-L/SUD manual by conducting a one-arm trial among Veterans with a SUD who report loneliness (n = 6), (2) randomize participants to receive either CBT-L/SUD (n = 15) or CBT-SUD (n = 15) to assess feasibility and acceptability among Veterans with a SUD who report loneliness. Methodology: the investigators will elicit feedback on a draft of the CBT-L/SUD manual then conduct a small single-arm trial (n = 6) for further refinement. Specifically, SUD treatment providers and Veterans with SUD will provide feedback on the draft manual, which the research team will integrate to finalize the manual for a small single-arm trial. This trial will allow us to collect feasibility of treatment delivery, and treatment satisfaction and acceptability data to further refine the manual. With the refined manual Veterans with SUD reporting loneliness will be randomized to either CBT-L/SUD (n = 15) or CBT-SUD (n = 15). The investigators will assess: (1) treatment acceptability, (2) participant adherence to treatment, and (3) therapist fidelity. The investigators will also assess outcome measure completion percentage, means and standard deviations, and level of correlation of repeated measurement of primary loneliness outcomes and secondary substance use outcomes. Implementation/Next Steps: Results from this study will provide critical feasibility and acceptability data to inform an HSR&D Merit Award application to conduct a fully-powered randomized controlled trial. The research team will work with the VA Office of Mental Health and Suicide Prevention and the Substance Use Disorder office of the National Mental Health Program to identify implementation and dissemination efforts. For example, the investigators plan to translate findings into applied practice across various settings (e.g., primary care mental health, rehabilitation treatment programs). Additionally, this intervention may be particularly useful for behavioral telehealth centers that deliver evidence-based interventions to rural and other Veterans who have difficulty accessing VHA care.

In this study, the investigators compared the improvement of immune function related indicators in patients with liver cirrhosis after laparoscopic splenectomy and azygoportal disconnection. To determine whether surgical treatment can help enhance postoperative immune function and improve patient prognosis.

Circulatory shock occurs when the supply of oxygen in the tissues decreases, which leads to cell damage and affects about one third of patients admitted to Intensive Care Units (ICU). Cardiac Output (CO) can be defined as the volume of blood ejected by the left ventricle per minute and is a very useful hemodynamic parameter in the monitoring of patients with signs of circulatory shock, since it can help define the etiology and management of such patients. Nevertheless, this parameter is underused in patients treated in Emergency Units, as its measurement usually involves invasive methods and few are available in this scenario. The pulmonary artery catheter is considered the gold standard method for determining the cardiac output, however, since it is an invasive method, in recent decades other devices capable of providing this hemodynamic variable in a less invasive way have been developed. Any method capable of providing CO without the need for pulmonary artery catheter insertion is called minimally invasive CO monitoring. The potential advantages of using these methods include the simplicity of measurements, faster acquisition of hemodynamic parameters and the possibility of implementing a monitoring strategy in places such as emergencies and emergency rooms. The evaluation of these parameters allows a faster determination of the etiology of circulatory shock, which enables the early initiation of goal-guided therapy. It is known that the use of goal-guided therapy proved to be effective in reducing peri- and postoperative morbidity and mortality in patients with high surgical risk; this strategy is also associated with reduced mortality, length of stay in the ICU and on mechanical ventilation in patients admitted to the ICU who are fluid responsive. To date, there is no data regarding the impact of a hemodynamic optimization strategy on patients in the first hours of shock. The investigators aim to assess whether goal-based hemodynamic therapy, through non-invasive hemodynamic monitoring, reduces the incidence of acute renal failure in patients with circulatory shock. A multicenter, randomized, open-label study will be carried out. The study will include patients over 18 years of age with signs of shock (systolic blood pressure less than 90 mmHg and/or mean arterial pressure less than 70 mmHg plus at least one of the following changes: lactate greater than 15 mg/dL, oliguria, neurological changes, and capillary refill time greater than 3 seconds) and who have signed an informed consent form (ICF). Included patients will be randomized in a 1:1 ratio into two groups. The Goal-Directed Therapy Group will be the one in which patients will be monitored by the ClearSight™ System (Edwards Life Sciences, Irvine, CA, USA) in the first 24 hours after randomization, where the parameters cardiac index (CI), systolic volume (SV), systolic blood pressure (SBP) and mean arterial pressure (MAP) will be used to determine medical management; if the CI is less than 2.2 L/min/m² and the SV less than 35 mL/beat, an aliquot of 500 mL of crystalloid solution will be administered; if the patient presents with CI less than 2.2 L/min/m², associated with SV greater than 35 mL/beat, dobutamine will be initiated; in patients with SBP less than 90 mmHg and/or MAP less than 70 mmHg, associated with SV greater than or equal to 35 mL/beat, norepinephrine will be initiated. In the Conventional Therapy group, the allocated patients will be treated according to the assistant team, where the following parameters will be evaluated: blood pressure, peripheral oximetry, heart rate, respiratory rate, and urine output; patients showing signs of hypovolemia will receive crystalloid solution; those who remain with hypotension refractory to volume replacement will be given vasoactive drugs; those with suggestive of cardiogenic shock will be given inotropic drugs; these procedures will be determined according to the clinical judgment of the assistant team.

This study is a Phase II study to determine the preliminary safety and efficacy of salvage radiation treatment after BCMA CAR-T therapy in subjects with RRMM. The study population will consist of subjects with RRMM previously treated with SOC BCMA CAR-T cell therapy with active disease on the D30+ PET or other imaging scan after CAR-T infusion. Patients who are planned for salvage chemotherapy less than 14 days after completion of radiation treatment will be excluded. Radiation treatment will be to bony or soft tissue plasmacytomas in up to five radiation treatment fields to 10-20Gy (or equivalent dose in 2Gy fractions of 10-21Gy). Final dose, target, and technique are per treating radiation physician discretion within these guidelines. Thirty patients will be enrolled. The co-primary endpoints are objective response rate (ORR) at 6 months and duration of response (DOR) among responders.

This phase II trial tests whether acalabrutinib in combination with venetoclax or obinutuzumab works to shrink tumors in patients with treatment-naive chronic lymphocytic leukemia . Acalabrutinib is also an inhibitor that works in the body to block the activation of certain cells that lead to the growth of cancerous B cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Obinutuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib in combination with venetoclax or obinutuzumab may help ease symptoms, decrease the amount of cancer suggestive of improvement, prolonged disease-free remission and/or survival, and increased knowledge about cancer treatment in patients with chronic lymphocytic leukemia. Patients will be treated with acalabrutinib for 12 cycles, and then randomized to receive 6 cycles of acalabrutinib plus obinutuzumab or acalabrutinib plus venetoclax.

The primary aim is to test whether abatacept, as compared to placebo, is associated with a reduction in major adverse cardiac events (MACE) among participants hospitalized with myocarditis secondary to an immune checkpoint inhibitor (ICI). The primary outcome, MACE, is a composite of first occurrence of cardiovascular death, non-fatal sudden cardiac arrest, cardiogenic shock, significant ventricular arrythmias, significant bradyarrythmias, or incident heart failure.