[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"molecular-mechanisms-of-pharmacological-action\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:molecular-mechanisms-of-pharmacological-action":38},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,7,0,[8,63,98,132,190,227,261],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":13,"acronym":4,"eligibilityCriteria":14,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":17,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":4,"briefSummary":22,"conditions":23,"keywords":45,"overallStatus":50,"whyStopped":4,"lastUpdateSubmitDate":51,"lastUpdatePostDateStruct":52,"startDateStruct":55,"completionDateStruct":57,"leadSponsor":59,"locationsCount":62},"100551600","natural-history-of-depression-bipolar-disorder-and-suicide-risk-100551600",false,"NCT06462196","Natural History of Depression, Bipolar Disorder and Suicide Risk","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Signed consent for Protocol 01-M-0254: The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers\n* Age 18 years or older\n* Able to provide informed consent\n* Able to read and write English\n\nEXCLUSION CRITERIA:\n\n* Unstable medical conditions in the opinion of the investigator that would preclude participation in outpatient or inpatient treatment.\n* Pregnancy\n* Participation in the Protocol 01-M-0254: The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers, as a healthy volunteer.\n* Participants with a history of DSM-IV substance or alcohol abuse or dependence, or DSM-5 substance use disorder (except for caffeine, nicotine, or cannabis), or moderate to severe alcohol use disorder, within the preceding three months. In addition, participants who are currently using drugs (except for caffeine, nicotine, or cannabis) must not have used illicit substances or known drugs of abuse in the two weeks prior to consent and must have a negative drug urine test (except for prescribed benzodiazepines or stimulants) prior to enrolling in the study. Cannabis use is exclusionary if the use is daily, or if participants are unable to abstain during the study, or if function of daily life is impaired by use as determined by a clinician.","ALL","18 Years","120 Years",{"count":19,"type":20},500,"ESTIMATED","OBSERVATIONAL","Mood disorders, such as depression and bipolar disorder, are difficult to treat. One reason is that there are no objective ways to measure how these disorders affect the body and respond to different treatments. In this study, researchers want to perform tests on people undergoing clinical care for mood disorders. The purpose is to understand the experience of receiving treatment for depression, bipolar disorder, and suicide risk. We also hope that this study will help us to predict which medications will improve thoughts of suicide.\n\nPeople 18 years or older who are receiving treatment for depression, bipolar disorder, or suicide risk may take part in this study. Participants must have also been enrolled in protocol 01-M-0254.\n\nThis study will be conducted at the NIH Clinical Center in Bethesda, MD. The study typically lasts up to 12 weeks, but may last longer if a participant s treatment continues past that time.\n\nParticipants will have weekly interviews and questionnaires while they are being treated for their mood disorder. Other tests are optional and include psychological testing, blood draws, sleep tests, and imaging scans. These will be done at the start and the end of research participation.",[24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44],"Behavioral Symptoms","Suicide","Self-Injurious Behavior","Sensory System Agents","Analgesics","Peripheral Nervous System Agents","Physiological Effects of Drugs","Anesthetics, Dissociative","Anesthetics, General","Anesthetics","Central Nervous System Depressants","Excitatory Amino Acid Antagonists","Excitatory Amino Acid Agents","Neurotransmitter Agents","Molecular Mechanisms of Pharmacological Action","Ketamine","Depression, Unipolar","Depressive Symptoms","Treatment Resistant Depression","Major Depressive Disorder","Depression, Bipolar",[46,25,43,47,48,49,42],"Neurobiology","Bipolar Disorder","Biomarkers","Suicide Risk","RECRUITING","2026-06-26",{"date":53,"type":54},"2026-06-29","ACTUAL",{"date":56,"type":54},"2024-09-09",{"date":58,"type":20},"2030-06-01",{"name":60,"class":61},"National Institute of Mental Health (NIMH)","NIH",1,{"id":64,"slug":65,"hasResults":11,"nctId":66,"briefTitle":67,"officialTitle":68,"acronym":4,"eligibilityCriteria":69,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":70,"enrollmentInfo":71,"targetDuration":4,"studyType":73,"phases":74,"briefSummary":76,"conditions":77,"keywords":84,"overallStatus":50,"whyStopped":4,"lastUpdateSubmitDate":90,"lastUpdatePostDateStruct":91,"startDateStruct":93,"completionDateStruct":95,"leadSponsor":97,"locationsCount":62},"100555424","phase-2-investigation-of-the-antidepressant-effects-of-2r6r-hnk-an-enhancer-of-synaptic-glutamate-release-in-treatment-resistant-depression-100555424","NCT06511908","Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression","An Investigation of the Antidepressant Effects of (2R,6R)-HNK, an Enhancer of Synaptic Glutamate Release, in Treatment-Resistant Depression","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n1. Ability of participant to understand and willingness to sign a written informed consent document. To verify this, participants must score \\>= 80% on the consent quiz.\n2. Stated willingness to comply with all study procedures and availability for the duration of the study.\n3. 18 to 70 years of age.\n4. All participants must have undergone a screening assessment under protocol 01-M-0254.\n5. Participants must fulfill DSM-IV or DSM-5 criteria for MDD, single episode or recurrent without psychotic features, based on clinical assessment and confirmed by a structured diagnostic interview (SCID-P). Participants must be experiencing a current major depressive episode lasting at least two weeks.\n6. Participants must have an initial score of \\>= 20 on the MADRS and a YMRS score of \\\u003C12 within one week of study entry and upon entry into Phase II.\n7. Ability to take intravenous medication and be willing to adhere to the (2R,6R)-HNK regimen.\n8. Participants must have a current or past history of lack of response to at least one adequate antidepressant trial (may be from the same chemical class), with at least one in the current major depressive episode, operationally defined using the modified Antidepressant Treatment History Form (ATHF); non-response to an adequate trial of ECT or TMS would count as an adequate antidepressant trial.\n9. For individuals of reproductive potential: use of highly effective contraception starting at the time of enrollment and agreement to use such a method during study participation and for an additional four weeks after the end of Study Phase II.\n10. For males of reproductive potential: use of condoms or other methods from the time of enrollment to ensure effective contraception with partner, and for an additional 90 days after the end of Phase II.\n11. Agreement to adhere to Lifestyle Considerations throughout study duration.\n12. Medically healthy, or with stable, treated, chronic medical conditions (provided any medications are not excluded)\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Current use of disallowed concomitant medications or transcranial magnetic stimulation (TMS) two weeks prior to the start of Phase II.\n2. Treatment with a reversible monoamine oxidase inhibitor (MAOI) four weeks prior to the start of Phase II.\n3. Treatment with fluoxetine, aripiprazole, or brexpiprazole five weeks prior to the start of Phase II.\n4. Treatment with clozapine or electroconvulsive therapy (ECT) four weeks prior to the start of Phase II.\n5. Ongoing treatment with moderate or strong CYP3A4\u002F5 inhibitors or inducers\n6. Lifetime history of deep brain stimulation.\n7. Previous antidepressant non-response to ketamine or esketamine (full course).\n8. No structured psychotherapy will be permitted during the total duration of the study. Participants unable or unwilling to stop psychotherapy will be unable to participate in the study.\n9. Pregnancy or lactation.\n10. Current psychotic features or a diagnosis of schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-5.\n11. Participants with a history of DSM-IV substance or alcohol abuse or dependence, or DSM-5 substance use disorder (except for caffeine, nicotine, or cannabis), or moderate to severe alcohol use disorder, within the preceding three months. In addition, participants who are currently using drugs (except for caffeine, nicotine, or cannabis) must not have used illicit substances or known drugs of abuse in the two weeks prior to screen and must have a negative drug urine test (except for prescribed benzodiazepines or stimulants) prior to starting Phase II. Cannabis use is exclusionary if the use is daily, or if participants are unable to abstain during the study, or if function of daily life is impaired by use as determined by a clinician. Due to the interactions between cannabis and SSRIs, frequent cannabis use during previous antidepressant treatment will result in that treatment being considered a failed trial for eligibility purposes.\n12. Participants with a DSM-IV or DSM-5 Axis II diagnosis of borderline or antisocial personality disorder.\n13. Participants with a history of head injury that resulted in loss of consciousness exceeding five minutes (for the imaging component of the study).\n14. No serious, unstable medical illnesses including but not limited to the following body systems and organs or those that in the judgment of the Principal Investigator pose a risk to the participant's ability to safely participate in the study: Hepatic diseases (e.g. active viral hepatitis infection or cirrhosis of the liver, any liver disease with Child-Pugh score \\>=5), cardiovascular disease (including ischemic heart disease, coronary artery disease, congestive heart failure, poorly controlled hypertension due to risk of further blood pressure elevation and increase in demand on cardiac function from study drug), renal\u002Furologic (e.g chronic kidney disease or acute kidney injury, history of bladder dysfunction due to theoretical risk of ketamine-induced cystitis, moderate to severe renal impairment of any etiology), endocrinologic (including uncontrolled diabetes due to association with progressive abnormality of the microvasculature and nervous system), or neurologic disease (e.g. elevated intraocular pressure or history of or presence of diseases that are associated with elevated intracranial pressure).\n15. Participants with unstable clinical hyperthyroidism or hypothyroidism.\n16. Participants with one or more seizures without a clear and resolved etiology.\n17. Clinically significant abnormal laboratory tests specifically defined by:\n\n    * Alkaline phosphatase (Alk Phos) \\> 150 U\u002FL\n    * Alanine aminotransferase (ALT) \\> 55 U\u002FL\n    * Aspartate aminotransferase (AST) \\> 34 U\u002FL\n    * Total bilirubin (TB) \\> 1.2 mg\u002FdL\n    * Direct bilirubin (DB) \\> 0.5 mg\u002FdL\n    * 25-hydroxyvitamin D \\\u003C 20 ng\u002FmL\n    * Folate \\\u003C 2ng\u002FmL\n    * Vitamin B12 \\\u003C 200 pg\u002FmL\n18. Moderate to severe renal impairment with body surface area corrected eGFR \\\u003C60mL\u002Fmin.\n19. Participants who, in the Principal Investigator's judgment, pose a current serious suicidal or homicidal risk.\n20. Positive HIV test.\n21. Contraindications to MRS (metal in body, claustrophobia, etc. for imaging)\n22. Participants with COVID-19 or suspected COVID-19\n23. Inability to read and understand English. Non- English speakers will not be eligible as most of the required monitoring and rating instruments are not validated in languages other than English.","70 Years",{"count":72,"type":20},50,"INTERVENTIONAL",[75],"PHASE2","Background:\n\nMajor depressive disorder (MDD) is a serious mental illness that can put people at risk of self-harm and death. Many drugs are used to treat MDD, but it can take a long time for them to be effective. Researchers want to know if a faster-acting drug, (2R,6R)-hydroxynorketamine (HNK), can better treat the symptoms of MDD.\n\nObjective:\n\nTo test a study drug (HNK) in people with MDD.\n\nEligibility:\n\nPeople aged 18 to 70 years with MDD. They must have had a screening assessment under protocol 01-M-0254.\n\nDesign:\n\nParticipants will be tapered off their current MDD drugs over 2 to 5 weeks. They will stay off of the drugs for up to 2 weeks prior to starting the study medication and procedures. They will have a physical exam with blood tests. They will have tests of their heart function, mood, and thinking. They will answer questions about their symptoms. They may choose to have imaging scans and scans of their brain activity.\n\nHNK is given through a tube attached to a needle inserted into a vein. Participants will receive infusions on this schedule:\n\nThey will receive 4 infusions over 2 weeks. They will stay in the clinical center overnight after each infusion or for the duration of the study.\n\nThey will receive no drugs for 2 to 3 weeks.\n\nThey will have 4 more infusions over 2 weeks, with overnight stays after each or for the duration of the study.\n\nOne set of 4 infusions will be the HNK. The other set of 4 infusions will be a placebo. A placebo looks just like the real drug but contains no medicine. Participants will not know when they are getting the HNK or placebo.\n\n...",[25,78,39,38,37,36,30,79,80,81,82,83,24],"Depressive Disorder, Treatment-Resistant","Depressive Disorder, Major","Depressive Disorder","Depression","Mental Disorders","Mood Disorders",[43,39,48,85,86,87,46,88,89],"Neuropharmacology","Magnetic Resonance Imaging","Magnetoencephalography","Glutamate","Hydroxynorketamine","2026-06-13",{"date":92,"type":54},"2026-06-16",{"date":94,"type":54},"2024-11-06",{"date":96,"type":20},"2027-07-01",{"name":60,"class":61},{"id":99,"slug":100,"hasResults":11,"nctId":101,"briefTitle":102,"officialTitle":103,"acronym":104,"eligibilityCriteria":105,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":106,"enrollmentInfo":107,"targetDuration":4,"studyType":73,"phases":109,"briefSummary":111,"conditions":112,"keywords":119,"overallStatus":50,"whyStopped":4,"lastUpdateSubmitDate":121,"lastUpdatePostDateStruct":122,"startDateStruct":124,"completionDateStruct":126,"leadSponsor":128,"locationsCount":131},"100609123","phase-3-a-study-of-nt-201-in-adults-with-moderate-to-severe-platysma-prominence-in-europe-platinum-eu-100609123","NCT07210463","A Study of NT 201 in Adults With Moderate to Severe Platysma Prominence in Europe (PLATINUM EU)","A Phase 3, Randomized, Parallel-group, Double-blind, Multicenter Study Investigating the Safety and Efficacy of NT 201 Compared With Placebo in Adult Participants With Moderate to Severe Platysma Prominence in Europe","PLATINUM EU","Inclusion Criteria:\n\n* Presence of four (medial and lateral, left and right) platysmal bands assessed at screening and baseline.\n* A score of Grade 3 ('moderate') or Grade 4 ('severe') on the MAPSD at maximum contraction by the investigator AND participant.\n\nExclusion Criteria:\n\n* Hypersensitivity or a history of allergic reaction to botulinum toxin of any serotype or any of their formulation ingredients.\n* Any medical condition that may put the participant at increased risk with exposure to botulinum toxin of any serotype, or any disorders that might interfere with neuromuscular function.\n* Any serious disease or disorder that could interfere with the safe completion of treatment or with study outcome assessments, or compromise participant safety.\n* Botulinum toxin treatment in the face (below the lower orbital rim), jawline, or neck within the last seven months.\n* History of lower face surgery, neck or chest surgery, and aesthetic procedures in the past 12 months and\u002For orthodontic procedures in the past 6 months.\n* Planned surgery or aesthetic procedures to the lower face, neck, or chest during the study period.\n* Anticipated need for treatment with botulinum toxin of any serotype for any indication during the study (other than study products).","65 Years",{"count":108,"type":20},300,[110],"PHASE3","The purpose of this study is to assess the safety and efficacy of NT 201 compared with placebo in participants with moderate to severe platysma prominence. The study will be conducted in two periods: Main Period (MP) and Open label Extension Period (OLEX).",[113,29,30,114,115,38,116,37,117,118],"Neuromuscular Agents","Acetylcholine Release Inhibitors","Membrane Transport Modulators","Cholinergic Agents","incobotulinumtoxinA","Botulinum Toxins, Type A",[120],"Platysma prominence","2026-06-10",{"date":123,"type":54},"2026-06-12",{"date":125,"type":54},"2025-10-01",{"date":127,"type":20},"2027-11",{"name":129,"class":130},"Merz Aesthetics GmbH","INDUSTRY",26,{"id":133,"slug":134,"hasResults":11,"nctId":135,"briefTitle":136,"officialTitle":137,"acronym":138,"eligibilityCriteria":139,"healthyVolunteers":11,"sex":15,"minAge":4,"maxAge":4,"enrollmentInfo":140,"targetDuration":4,"studyType":73,"phases":142,"briefSummary":144,"conditions":145,"keywords":169,"overallStatus":50,"whyStopped":4,"lastUpdateSubmitDate":180,"lastUpdatePostDateStruct":181,"startDateStruct":183,"completionDateStruct":185,"leadSponsor":187,"locationsCount":62},"100557242","single-vs-dual-antiplatelet-therapy-in-elderly-or-hbr-patients-undergoing-percutaneous-intervention-with-dcb-piccoleto-iv-epic-38-100557242","NCT06535568","Single vs. Dual Antiplatelet Therapy in Elderly or HBR Patients Undergoing Percutaneous Intervention With DCB (PICCOLETO IV-EPIC 38)","International, Multicenter, Investigator-driven Randomized Clinical Trial to Assess the Single vs. Dual Antiplatelet Therapy in Elderly or HBR Patients Undergoing Percutaneous Intervention With Drug-coated Balloons (PICCOLETO IV-EPIC 38)","PIV-EPIC","Inclusion Criteria:\n\nMale and female patients who meet the following criteria:\n\n* Age ≥ 75 years or age ≥ 18 years at high bleeding risk;\n* Successful PCI with Essential Pro DCB just performed, in 1, 2 or 3 coronary vessels;\n* Stable or unstable coronary syndromes;\n* De novo coronary lesions in vessels with diameter ≥2.0 and ≤4.0 mm (visual estimation);\n* Informed consent to participate in the study given by the patient or impartial witness.\n\nExclusion Criteria:\n\n* Stent implantation during index or recent (\\\u003C6 months) procedure;\n* Known (and untreatable) hypersensitivity or contraindication to aspirin, heparin, clopidogrel, paclitaxel or contrast media, or any of their excipient which cannot be adequately pre-medicated;\n* Pregnancy at the time of hospitalization;\n* Patients participating in another clinical study in which an investigational drug or device was administered within 30 days of screening or within the 5 half-lives of the study drug, whichever is longer;\n* ST-elevation myocardial infarction;\n* Life expectancy \\\u003C12 months;\n* Left ventricular ejection fraction \\\u003C30%;\n* Visible thrombus at lesion site;\n* Target lesion\u002Fvessel with any of the following characteristics:\n\n  * severe and\u002For \\>270° calcification of the target vessel, also proximal to the lesion (intravascular imaging not mandatory);\n  * left main stem stenosis \\>50%;\n  * target lesion is in the left main stem;\n  * chronic total occlusion with anticipated necessity of retrograde approach;\n  * lesion is in a bypass graft.\n* History of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines (NSAIDs);\n* History of gastrointestinal perforation, ulceration, or bleeding (peptic ulcer bleeding-PUBs) related to previous use of NSAIDs or anticoagulant medications, or intracranial hemorrhage;\n* Acute gastrointestinal ulcers;\n* Hemorrhagic diathesis (including known bleeding disorders or ongoing active bleeding);\n* Severe renal impairment (eGFR \\\u003C 30 mL\u002Fmin);\n* Severe hepatic impairment (Child-Pugh C), with elevated liver enzymes (ALT\u002FAST \\> 2 x ULN or total bilirubin \\>1.5 x ULN);\n* Severe cardiac failure (NYHA grade III or IV);\n* Combination with methotrexate at doses of 15 mg\u002Fweek or more;\n* Patients with baseline neutrophil counts \\\u003C 1500 cells\u002Fmm³;\n* Breastfeeding women;\n* Full-blown thyrotoxicosis;\n* Patients with a very high risk of thrombosis.",{"count":141,"type":20},576,[143],"NA","This international, multicenter, open-label, randomized clinical trial evaluates the safety and efficacy of single antiplatelet therapy (SAPT) compared to dual antiplatelet therapy (DAPT) in elderly or high bleeding risk patients undergoing percutaneous coronary intervention (PCI) with the latest generation drug-coated balloon (DCB). The study includes patients with stable or unstable coronary syndromes and aims to assess rates of ischemic and bleeding adverse events.",[146,147,148,149,150,151,152,153,154,155,38,156,157,158,30,159,160,161,162,163,164,165,166,167,168],"Coronary Disease","Heart Diseases","Cardiovascular Diseases","Myocardial Ischemia","Atherosclerosis","Arterial Occlusive Diseases","Vascular Diseases","Coronary Artery Disease","Acute Coronary Syndrome","Coronary Stenosis","Enzyme Inhibitors","MTOR Inhibitors","Protein Kinase Inhibitors","Immunosuppressive Agents","Antineoplastic Agents","High Bleeding Risk","Single Antiplatelet Therapy","Dual Antiplatelet Therapy","Cyclooxygenase Inhibitors","P2Y12 Inhibitor","Platelet Aggregation Inhibitors","Aspirin","Clopidogrel",[170,171,172,173,174,175,176,177,178,179],"DCB","Angioplasty","Paclitaxel","Antiplatelet treatment","Single antiplatelet therapy (SAPT)","Dual antiplatelet therapy (DAPT)","High bleeding risk (HBR)","MACE","Native CAD","stable or unstable coronary syndromes","2026-01-21",{"date":182,"type":54},"2026-01-22",{"date":184,"type":54},"2026-01-10",{"date":186,"type":20},"2028-02-20",{"name":188,"class":189},"Fondazione Ricerca e Innovazione Cardiovascolare ETS","OTHER",{"id":191,"slug":192,"hasResults":11,"nctId":193,"briefTitle":194,"officialTitle":195,"acronym":196,"eligibilityCriteria":197,"healthyVolunteers":11,"sex":15,"minAge":198,"maxAge":4,"enrollmentInfo":199,"targetDuration":4,"studyType":73,"phases":201,"briefSummary":203,"conditions":204,"keywords":4,"overallStatus":50,"whyStopped":4,"lastUpdateSubmitDate":217,"lastUpdatePostDateStruct":218,"startDateStruct":220,"completionDateStruct":222,"leadSponsor":224,"locationsCount":226},"100384702","phase-4-cognitive-outcomes-after-dexmedetomidine-sedation-in-cardiac-surgery-patients-100384702","NCT04289142","Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients","Cognitive Outcomes After Dexmedetomidine Sedation in Cardiac Surgery Patients: CODEX Trial","CODEX","Inclusion Criteria:\n\n* Planned CABG (+\u002F- valve, including off-pump) or valve replacement via sternotomy\u002Fthoracotomy, with initial recovery in the Cardiovascular Intensive Care Unit (CVICU)\n* Age ≥60\n\nExclusion Criteria:\n\n* Lack of patient consent\n* Pre-operative major cognitive dysfunction (CogState Brief Battery score \\\u003C 80) at screening\n* Aortic arch replacement\u002Fre-implantation (surgery requiring hypothermic circulatory arrest, e.g. Bentall procedure)\n* Allergy\u002Fcontraindication to dexmedetomidine (untreated 2nd degree type 2 or 3rd degree heart block (pacemaker), cirrhosis, HR \\\u003C 50 , grade 4 LV, renal failure or on renal replacement therapy)\n* Unlikely to comply with study assessments (e.g. no fixed address, cannot complete cognitive tests at the 3, 6, and 12 month time points)","60 Years",{"count":200,"type":20},2400,[202],"PHASE4","Anesthesia is a drug induced, reversible, comatose state that facilitates surgery and it is widely assumed that cognition returns to baseline after anesthetics have been eliminated. However, many patients have persistent memory impairment for weeks to months after surgery. Cardiac surgery appears to carry the highest risk of postoperative cognitive dysfunction (POCD). These cognitive deficits are associated with increased mortality, prolonged hospital stay and loss of independence. The investigators propose to investigate the role of Dexmedetomidine (DEX) in preventing long-term POCD after cardiac surgery and enhancing early postoperative recovery. It is anticipated that DEX will be the first effective preventative therapy for POCD, improve patient outcomes, and reduce length of stay and healthcare costs.",[205,206,207,208,82,209,210,211,212,213,214,215,34,30,216,28,38],"Delirium","Cognitive Dysfunction","Cognition Disorder","Neurocognitive Disorders","Confusion","Neurobehavioral Manifestations","Neurologic Manifestations","Nervous System Diseases","Signs and Symptoms","Dexmedetomidine","Hypnotics and Sedatives","Analgesics, Non-Narcotic","2025-11-27",{"date":219,"type":54},"2025-12-01",{"date":221,"type":54},"2019-12-01",{"date":223,"type":20},"2029-03",{"name":225,"class":189},"Sunnybrook Health Sciences Centre",8,{"id":228,"slug":229,"hasResults":11,"nctId":230,"briefTitle":231,"officialTitle":232,"acronym":4,"eligibilityCriteria":233,"healthyVolunteers":11,"sex":15,"minAge":16,"maxAge":4,"enrollmentInfo":234,"targetDuration":4,"studyType":73,"phases":235,"briefSummary":237,"conditions":238,"keywords":247,"overallStatus":50,"whyStopped":4,"lastUpdateSubmitDate":251,"lastUpdatePostDateStruct":252,"startDateStruct":254,"completionDateStruct":256,"leadSponsor":258,"locationsCount":260},"100406441","phase-1-safety-of-sbrt-with-anti-pd1-and-anti-il-8-for-the-treatment-of-multiple-metastases-in-advanced-solid-tumors-and-melanoma-100406441","NCT04572451","Safety of SBRT With Anti-PD1 and Anti-IL-8 for the Treatment of Multiple Metastases in Advanced Solid Tumors and Melanoma","Phase I Study Investigating the Safety of Stereotactic Body Radiotherapy (SBRT) With Anti-PD1 and Anti-IL-8 for the Treatment of Multiple Metastases in Advanced Solid Tumors and Melanoma","Inclusion Criteria:\n\n* SAFETY COHORT\n\n  1. Patients with advanced\u002Fmetastatic\u002Funresectable solid tumors progressed on standard therapies. Patients with melanoma and RCC will make up approximately 30% of total cohort.\n  2. Patients with 1-4 tumor sites that can be irradiated safely\n  3. Age \\> or equal 18 years\n  4. ECOG performance status 0 or 1\n  5. Patients must have normal organ and marrow function as defined below:\n\n     * Leukocytes ≥ 3000\u002FmcL;\n     * absolute neutrophil count ≥ 1500\u002FmcL;\n     * Platelets ≥ 100,000\u002FmcL;\n     * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × upper limit of normal (ULN) ;\n     * Total bilirubin ≤ 1.5 × ULN (except participants with Gilbert's Syndrome who must have normal direct bilirubin)\n     * Serum creatinine ≤ 1.5 × ULN Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam\n  6. Ability to understand and the willingness to sign a written informed consent document.\n  7. Reproductive status\n\n     * Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU\u002FL or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study treatment.\n     * Women must not be breastfeeding.\n     * WOCBP must agree to follow instructions for method(s) of contraception (Appendix 5) for the duration of study treatment plus 5 half-lives of nivolumab plus 30 days (duration of ovulatory cycle), for a total of 155 days post treatment completion. Local laws and regulations may require use of alternative and\u002For additional contraception methods.\n     * WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, but should still undergo pregnancy testing as described in this section.\n     * Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception (Appendix4) during combination treatment with study treatment BMS-986253 and nivolumab, plus 5 half-lives of nivolumab (∼125 days), plus 90 days (duration of sperm turnover), for a total of 215 days post-treatment completion. In addition, male participants must be willing to refrain from sperm donation during this time.\n* EFFICACY COHORT\n\n  1. Patients with anti-PD1\u002FPDL1 refractory melanoma\n  2. Patients with 1-4 tumor sites that can be irradiated safely\n  3. Age ≥ 18 years\n  4. ECOG performance status 0 or 1\n  5. Patients must have normal organ and marrow function as defined above for safety cohort\n  6. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non- nodal lesions and short axis for nodal lesions) as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam\n  7. Ability to understand and the willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n1. Known or suspected CNS metastases, with the following exceptions:\n\n   a) Subjects with controlled brain metastases will be allowed to enroll. Controlled brain metastases are defined as no radiographic progression for at least 4 weeks following 18 radiation and\u002For surgical treatment at the time of randomization. b) Subjects must be off steroids for at least 2 weeks prior to initiation of investigational therapy c) Subjects with signs or symptoms of brain metastases are not eligible unless brain metastases are ruled out by computed tomography or magnetic resonance imaging.\n2. Medical History and Concurrent Diseases\n\n   * Patients who are receiving any other investigational agents.\n   * History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab and BMS-986253\n   * Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.\n   * Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:\n\n     i. Myocardial infarction (MI) or stroke\u002Ftransient ischemic attack (TIA) within the 6 months prior to consent ii. Uncontrolled angina within the 3 months prior to consent iii. Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation) within a month prior to consent iv. QTc prolongation \\> 480 msec v. History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association \\[NYHA\\] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc) vi. Cardiovascular disease-related requirement for daily supplemental oxygen vii. History of two or more coronary revascularization procedures within the 3 months prior to consent viii. Subjects with history of myocarditis, regardless of etiology\n   * A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent\n   * Subjects with history of life-threatening toxicity related to prior immune therapy (eg. anti-CTLA-4 or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-occur with standard countermeasures (eg, hormone replacement after endocrinopathy).\n   * Subject has been administered prior chemotherapy or immunotherapy at any time, and any with radiation therapy within 4 weeks prior to time of consent or who has not recovered (ie, ≤ Grade 1 or at baseline) from adverse events due to previously administered agent.\n\n     1. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.\n     2. Subjects with endocrinopathy which is adequately controlled with hormone replacement therapy are an exception to this criterion and may qualify for the study.\n   * If subject underwent major surgery, subject must have recovered adequately from the toxicity and\u002For complications from the intervention prior to starting therapy.\n   * Subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.\n   * A known or underlying medical condition that, in the opinion of the investigator could make the administration of study drug hazardous to the subject or could adversely affect the ability of the subject to comply with or tolerate study therapy.\n   * Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated with the study drugs.\n   * Subjects who are unable to undergo venipuncture and\u002For tolerate venous access\n   * Evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days prior to initiation of study drug therapy\n   * Subjects who are on immunosuppressive therapy (systemic steroids 10mg and more daily use)\n   * Prisoners or subjects who are involuntarily incarcerated\n   * Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness\n   * Inability to comply with restrictions and prohibited activities and treatments",{"count":72,"type":20},[236],"PHASE1","Nivolumab (and other agents affecting the anti-programmed death-1 \\[anti-PD-1\\] pathway) have demonstrated anti-tumor activity in multiple tumor types. Combinations of immune-oncology (IO) agents with complimentary mechanisms as well as radiation represent a promising strategy to improve response rates to immunotherapy and overcome resistance. In this phase I\u002FIb study, radiation will be used in combination with IO agents nivolumab and anti-IL-8 (BMS-986253) to assess toxicity by organ system and then assess the preliminary efficacy of the treatment regimen. In Part 1, the study will determine the safe doses of radiation by organ site in conjunction with nivolumab and BMS-986253. In Part 2, the treatment regimen will be investigated in melanoma, prioritizing acral melanoma, to describe the response rate to treatment as well as other clinical and safety outcomes. The study will also provide the opportunity to evaluate changes in the tumor microenvironment induced by the treatment.",[239,240,241,242,243,244,160,245,38,246],"Melanoma","Unresectable Solid Tumors","Neoplasms","Neoplasms by Histologic Type","Neoplasms by Site","Antineoplastic Agents, Immunological","Immune Checkpoint Inhibitors","Nivolumab",[248,249,250],"Anti-PD-1 monoclonal antibody (mAb)","Anti-IL-8","Stereotactic Body Radiotherapy (SBRT)","2025-07-29",{"date":253,"type":54},"2025-08-01",{"date":255,"type":54},"2021-11-29",{"date":257,"type":20},"2027-05-31",{"name":259,"class":189},"Yana Najjar",2,{"id":262,"slug":263,"hasResults":11,"nctId":264,"briefTitle":265,"officialTitle":266,"acronym":4,"eligibilityCriteria":267,"healthyVolunteers":11,"sex":268,"minAge":16,"maxAge":4,"enrollmentInfo":269,"targetDuration":4,"studyType":73,"phases":271,"briefSummary":272,"conditions":273,"keywords":286,"overallStatus":50,"whyStopped":4,"lastUpdateSubmitDate":294,"lastUpdatePostDateStruct":295,"startDateStruct":297,"completionDateStruct":299,"leadSponsor":301,"locationsCount":303},"100474986","phase-4-sacubitrilvalsartan-in-primary-prevention-of-the-cardiotoxicity-of-systematic-breast-cancer-treatment-mainstream-100474986","NCT05465031","Sacubitril\u002FValsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent (MAINSTREAM)","Sacubitril\u002FValsartan in PriMAry preventIoN of the Cardiotoxicity of Systematic breaST canceR trEAtMent","Inclusion Criteria:\n\n* Written informed consent\n* Female gender, aged 18 years and over\n* Patients with histologically confirmed breast cancer and complete assessment of tumor phenotype (Estrogen receptor - ER, Progesterone receptor - PR, Human epidermal growth factor receptor 2 - HER2, Kiel - Ki67)\n* Ability to take oral medication and willingness to adhere to the planned regimen\n* Tumor grade IA-IIIC or oligometastatic grade IV\n* Radical treatment plan including surgery\n* Plan of use of systemic treatment (preoperative, postoperative or combined) with anthracyclines and\u002For anti-HER2 drugs\n* Eastern Cooperative Oncology Group (ECOG) 0-2 general status\n* LVEF ≥ 50% as assessed by echocardiography\n* Sinus rhythm\n\nExclusion Criteria:\n\n* Prior anthracycline-based chemotherapy and\u002For thoracic radiotherapy (prior to diagnosis of the cancer being the present cause of therapy)\n* Clinically relevant HF (NYHA II-IV)\n* Myocardial infarction (MI) within the last \\\u003C 3 months\n* Symptomatic hypotension or systolic blood pressure (SBP) \\\u003C 90 mmHg\n* Significant valvular disease, symptomatic coronary artery disease (CCS\\>2), significant atrioventricular (AV) block, symptomatic sinus node dysfunction\n* Expected survival \\\u003C12 months\n* Glomerular filtration rate (GFR) \\\u003C30 ml\u002Fmin\u002F1.73 m2 (screening visit)\n* K+\\>5.5mmol\u002FL (screening visit)\n* Contraindications to angiotensin converting enzyme inhibitor (ACE-I)\u002Fangiotensin II receptor blocker (ARB) or LCZ696 if not listed among criteria\n* Active untreated liver disease\n* Pregnancy\n* Conditions\u002Fcircumstances that may lead to non-compliance with medical staff recommendations (e.g. active drug\u002Falcohol dependence, poorly controlled mental illness)","FEMALE",{"count":270,"type":20},600,[202],"Breast cancer is the most commonly cancer in women in the overall global population. According to the World Cancer Research Fund International, there were more than 2.25 million new cases of breast cancer in women in 2020. Although the modern treatment strategies, based on the complex care, which consists of surgery, radiotherapy, hormone therapy, and targeted chemotherapy directed at specific cancer molecules have substantially reduced the risk of death due to breast cancer, their wide adoption results in the wider prevalence of cardiotoxicity, defined as either symptomatic heart failure, or asymptomatic contractile dysfunction. The occurrence of cardiotoxicity induced by anti-cancer therapies is estimated at 5-15%, and its development is the primary cause of therapy termination, which significantly reduces the probability of the efficacy of treatment. Several attempts have been made to determine the efficacious preventive strategy, which could diminish the risk of cancer-therapy induced cardiotoxicity. The results of the prior studies indicated a trend towards lower risk of troponin elevation, or left ventricular contractile dysfunction with the introduction of drugs interfering with the renin-angiotensin-aldosterone (RAA) axis, which constitute the primary treatment modality in heart failure with reduced ejection fraction (HFrEF). Sacubitril\u002Fvalsartan, the novel therapeutic agent, has been demonstrated to significantly improve prognosis in patients with HFrEF. Prior retrospective, small, single-center studies have shown that treatment with sacubitril\u002Fvalsartan may reduce the risk of cancer-therapy induced cardiotoxicity, or reverse contractile dysfunction caused by anti-cancer therapy. However, no large randomized data confirmed these findings.\n\nTherefore, the Sacubitril\u002FValsartan in PriMAry preventIoN of the cardiotoxicity of systematic breaST canceR trEAtMent) study, has been designed to verify, whether the preventive use of sacubitril\u002Fvalsartan administered in the doses recommended in patients with HFrEF in breast cancer patients undergoing adjuvant chemotherapy with anthracyclines or anthracyclines and HER-2 monoclonal antibodies, will reduce the incidence of cardiotoxicity defined as impaired left ventricular systolic function on transthoracic echocardiography (TTE). In the trial, a total of 480 patients with histologically confirmed breast cancer, who are eligible for chemotherapy with anthracyclines or anthracyclines and HER-2 monoclonal antibodies, will undergo 1:1 randomization to either preventive treatment with sacubitril\u002Fvalsartan or placebo. The patients will be followed for 24 months, and will have repetitive efficacy and safety examinations, including echocardiography, MRI (optionally), electrocardiography including 24-h Holter monitoring, blood tests, functional capacity tests and quality of life assessment.",[274,275,276,277,278,279,280,38,281,282,283,284,285],"Breast Cancer","Neoplasm, Breast","Breast Diseases","Antihypertensive Agents","Sacubitril\u002FValsartan","Angiotensin II Type 1 Receptor Blockers","Angiotensin Receptor Antagonists","Heart Failure","Cardiac Toxicity","Cancer, Therapy-Related","Cancer Therapy-Related Cardiac Dysfunction","Cardiotoxicity",[287,278,86,288,289,274,285,290,291,292,293],"LCZ696","Echocardiography","Cardio-oncology","Anthracyclines","Trastuzumab","Heart failure","Cardioprotection","2025-03-11",{"date":296,"type":54},"2025-03-14",{"date":298,"type":54},"2024-04-17",{"date":300,"type":20},"2029-02",{"name":302,"class":189},"Silesian Centre for Heart Diseases",4]