[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100565535":3},{"organization":4,"outcomesModule":7,"designInfo":100,"detailedDescription":107,"studyPopulation":103,"armGroups":108,"interventions":115,"overallOfficials":103,"centralContacts":103,"locations":121,"responsibleParty":135,"collaborators":139,"id":145,"slug":103,"hasResults":146,"nctId":147,"briefTitle":148,"officialTitle":149,"acronym":150,"eligibilityCriteria":151,"healthyVolunteers":146,"sex":152,"minAge":153,"maxAge":154,"enrollmentInfo":155,"targetDuration":103,"studyType":158,"phases":159,"briefSummary":161,"conditions":162,"keywords":103,"overallStatus":164,"whyStopped":103,"lastUpdateSubmitDate":165,"lastUpdatePostDateStruct":166,"startDateStruct":169,"completionDateStruct":171,"leadSponsor":173,"locationsCount":174},{"fullName":5,"class":6},"Centre Hospitalier Universitaire Vaudois","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":26,"otherOutcomes":80},[9,13,16,19,22],{"measure":10,"description":11,"timeFrame":12},"Pharmacokinetics - apparent clearance (CL\u002FF)","Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \\& simulation techniques).\n\nBasing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including CL\u002FF).","Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)",{"measure":14,"description":15,"timeFrame":12},"Pharmacokinetics - apparent (central) volume of distribution (Vd\u002FF)","Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \\& simulation techniques).\n\nBasing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including Vd\u002FF).",{"measure":17,"description":18,"timeFrame":12},"Pharmacokinetics - half-life","Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \\& simulation techniques).\n\nBasing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including t1\u002F2).",{"measure":20,"description":21,"timeFrame":12},"Pharmacokinetics - AUC","Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \\& simulation techniques).\n\nBasing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including AUC).",{"measure":23,"description":24,"timeFrame":25},"Pharmacokinetics - maximal concentration (Cmax)","Empagliflozin concentrations at the different time-points (6 samples at Visit 1, 1 opportunistic sample at Visits 2 and 3; the timing of the samples will be optimized with modeling \\& simulation techniques).\n\nBasing on these concentrations, non-compartmental pharmacokinetic calculations will be performed, allowing to determine pharmacokinetic parameters (including Cmax).","Time Frame: Visit 1 to Visit 3 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks after study start)",[27,31,34,37,40,44,47,50,54,57,60,63,67,70,74,77],{"measure":28,"description":29,"timeFrame":30},"Safety 1 - eGFR","Creatinine, respectively Cystatin C, will be collected in order to calculate eGFR (bedside Schwartz formula, respectively Filler equation).","Visit 1 to Visit 5 (Visit 1 = day 1, Visit 2 = 1 week, Visit 3 = 5-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)",{"measure":32,"description":33,"timeFrame":30},"Safety 2 - Occurrence of hypoglycemia","Blood glucose will be checked three times at Visit 1 (baseline, at approximately 2-3h post-intake, and before discharge at 8h post-intake), as well as once at Visits 2 to 5. Outcome measure: number of patients experiencing hypoglycemia.",{"measure":35,"description":36,"timeFrame":30},"Safety 3 - Occurrence of ketoacidosis","The outcome is presence (or absence) of ketoacidosis. This will be assessed at Visits 1, 2, 3, 4 and 5. Outcome measure: number of patients experiencing ketoacidosis.",{"measure":38,"description":39,"timeFrame":30},"Safety 4 - Occurrence of UTI","The outcome is presence (or absence) of UTI diagnosis. This will be assessed at Visits 1, 2, 3, 4 and 5. Outcome measure: number of patients experiencing UTI between Visit 2 and Visit 5.",{"measure":41,"description":42,"timeFrame":43},"Ease of swallow","Ease of swallow will be assessed by means of facial hedonic scales, according to our standard procedure, at Visit 1. (Scale 1 to 4, 1 being the worse and 4 the best score: very difficult - difficult - possible - easy to swallow.)","Visit 1 (Visit 1 = day 1)",{"measure":45,"description":46,"timeFrame":30},"Efficacy and efficacy markers (exploratory) 1 - Heart failure severity class","Symptoms, clinical signs, NYHA (if \\> or =8 years of age) \u002F Ross (if \\\u003C8 years of age) class assignment. NYHA and Ross heart failure classes share the same scale of I (no limitation of physical activity) to IV (symptoms at rest). Analysis will be performed at Visit 1, Visit 4 and Visit 5. Outcome: change between Visit 1 and Visit 5.",{"measure":48,"description":49,"timeFrame":30},"Efficacy and efficacy markers (exploratory) 2 - NT-proBNP level","Analysis will be performed at Visits 1, 3, 4 and 5. Outcome: change between Visit 1 and Visit 5.",{"measure":51,"description":52,"timeFrame":53},"Efficacy and efficacy markers (exploratory) 3 - Echocardiography 1: Left-ventricular end-diastolic diameter (LVEDd)","LVEDd (z-score) will be measured at Visits 1, 4 and 5. Outcome: change between Visit 1 and Visit 5.","Visits 1, 4 and 5 (Visit 1 = day 1, Visit 4 = 3 months, Visit 5 = 6 months after enrolment)",{"measure":55,"description":56,"timeFrame":53},"Efficacy and efficacy markers (exploratory) 4 - Echocardiography 2: Left-ventricular end-systolic diameter (LVESd)","LVESd (z-score) will be measured at Visits 1, 4 and 5. Outcome: change between Visit 1 and Visit 5.",{"measure":58,"description":59,"timeFrame":53},"Efficacy and efficacy markers (exploratory) 5 - Echocardiography 3: Fractional shortening (FS)","FS (%) will be measured at Visits 1, 4 and 5. Outcome: change between Visit 1 and Visit 5.",{"measure":61,"description":62,"timeFrame":53},"Efficacy and efficacy markers (exploratory) 6 - Echocardiography 4: Left ventricular ejection fraction (LV-EF)","LV-EF (%) will be measured at Visits 1, 4 and 5. Outcome: change between Visit 1 and Visit 5.",{"measure":64,"description":65,"timeFrame":66},"Efficacy and efficacy markers (exploratory) 7 - cMRI 1: Left ventricular end-diastolic volume","LV end-diastolic volume will be measured at Visits 1 and 5. Outcome: change between Visit 1 and Visit 5.","Visit 1, Visit 5 (Visit 1 = day 1, Visit 5 = 6 months after enrolment)",{"measure":68,"description":69,"timeFrame":66},"Efficacy and efficacy markers (exploratory) 8 - cMRI 2: Left ventricular end-systolic volume","LV end-systolic volume will be measured at Visits 1 and 5. Outcome: change between Visit 1 and Visit 5.",{"measure":71,"description":72,"timeFrame":73},"Efficacy and efficacy markers (exploratory) 9 - cMRI 3: Left ventricular ejection fraction","LV end-systolic ejection fraction will be measured\u002Fcalculated at Visits 1 and 5. Outcome: change between Visit 1 and Visit 5.","Visit 1, Visit 5 (Visit 1 = day 1, Visit 5 = 6 months after enrolment",{"measure":75,"description":76,"timeFrame":66},"Efficacy and efficacy markers (exploratory) 10 - cMRI 4: Presence of late gadolinium enhancement","Presence (y) or absence (n) of late gadolinium enhancement in each of the 17 AHA segments will be measured at Visits 1 and 5. Outcome: change in number of LGE positive segments between Visit 1 and Visit 5.",{"measure":78,"description":79,"timeFrame":66},"Efficacy and efficacy markers (exploratory) 11 - cMRI 5: Extracellular volume (ECV)","Extracellular volume (ECV) will be measured\u002Fcalculated at Visits 1 and 5. Outcome: change between Visit 1 and Visit 5.",[81,85,88,91,94,97],{"measure":82,"description":83,"timeFrame":84},"Efficacy markers (exploratory), Mechanistic insights - 1: body weight (kg)","To explore the effect of SGLT2 inhibitors on fluid status, body weight will be assessed (outcome: change between Visit 1 and Visit 5).","Visit 1 to Visit 5 (Visit 2 = 1 week, Visit 3 = 4-6 weeks, Visit 4 = 3 months, Visit 5 = 6 months)",{"measure":86,"description":87,"timeFrame":84},"Efficacy markers (exploratory), Mechanistic insights - 2: heart rate (bpm)","To explore the effect of SGLT2 inhibitors on sympathetic activation, heart rate (in bpm) will be assessed (outcome: change between Visit 1 and Visit 5).",{"measure":89,"description":90,"timeFrame":84},"Efficacy markers (exploratory), Mechanistic insights - 3: blood pressure (SBP\u002FDBP, mmHg)","To explore the effect of SGLT2 inhibitors on sympathetic activation, blood pressure (SBP and DBP, in mmHg) will be assessed (outcome: change between Visit 1 and Visit 5).",{"measure":92,"description":93,"timeFrame":84},"Efficacy markers (exploratory), Mechanistic insights - 4: b-hydroxybutyrate (mmol\u002FL)","To explore the effect of SGLT2 inhibitors on metabolism shift, b-hydroxybutyrate will be assessed (outcome: change between Visit 1 and Visit 5).",{"measure":95,"description":96,"timeFrame":84},"Efficacy markers (exploratory), Mechanistic insights - 5: haemoglobin (g\u002FL)","To explore the effect of SGLT2 inhibitors on haemoglobin, haemoglobin will be assessed (outcome: change between Visit 1 and Visit 5).",{"measure":98,"description":99,"timeFrame":84},"Efficacy markers (exploratory), Mechanistic insights - 6: uric acid (mmol\u002FL)","To explore the effect of SGLT2 inhibitors on uric acid homeostasis, uric acid will be assessed (outcome: change between Visit 1 and Visit 5).",{"allocation":101,"interventionModel":102,"interventionModelDescription":103,"primaryPurpose":104,"observationalModel":103,"timePerspective":103,"maskingInfo":105},"NA","SINGLE_GROUP",null,"TREATMENT",{"masking":106,"maskingDescription":103,"whoMasked":103},"NONE","Cardiac disease represents the main life-limiting condition in Duchenne muscular dystrophy (DMD). It is important to recognize and address this early in the disease course. Because of lack of DMD specific drugs, present attitudes for established DMD-related cardiomyopathy ground on current treatment for heart failure. Unfortunately, however, current heart failure therapy in Paediatrics is still unsatisfactory, with high in-hospital (7-26%), and 5-year mortality (30%-50%). Furthermore, mortality rate for DMD cardiomyopathy is worse than similarly aged idiopathic dilated cardiomyopathy (DCM) patients.\n\nAmong the recent improvements in adult heart failure management, the sodium glucose transporter type 2 inhibitors (SGLT2i) dapagliflozin and empagliflozin were found to reduce cardiovascular death or worsening heart failure by 25% on top of optimal medical therapy. Indeed, since 2021, they have been recommended as part of standard heart failure therapy.\n\nIn the past, paediatric heart failure trials often failed, mainly because of suboptimal dose or inappropriate formulations and endpoints.\n\nThis phase II.a, open-label trial is designed to characterize pharmacokinetics (primary outcome), ease-of-swallow, safety and explore potential efficacy markers (secondary outcomes) of empagliflozin in 12 children and adolescents with DMD-related cardiomyopathy, so to inform the design and performance of subsequent, state-of-the-art, high-quality efficacy trials.\n\nParticipants will receive empagliflozin during 6 months. They will have 5 visits, one end-study visit and 7 to 8 pharmacokinetic samples. The timing of these samples will be optimized exploiting contemporary modeling and simulation techniques.\n\nSafety evaluation will occur throughout the study, while ease-of-swallow will be evaluated at Visit 1, and efficacy markers at Visits 1, 4 and 5.\n\nPharmacokinetic modeling will characterize primary and secondary pharmacokinetic parameters and allow to define the optimal paediatric dose, informing both current compassionate-care use and the design of future efficacy trials.",[109],{"label":110,"type":111,"description":112,"interventionNames":113},"Empagliflozin","EXPERIMENTAL","All participants will receive the IMP (open-label trial, primary outcome PK)",[114],"Drug: Empagliflozin Tablets",[116],{"type":117,"name":118,"description":119,"armGroupLabels":120,"otherNames":103},"DRUG","Empagliflozin Tablets","Empagliflozin 10mg p.o. once daily (commercially available tablet)",[110],[122],{"facility":123,"status":103,"city":124,"state":125,"zip":126,"country":127,"countryCode":128,"cosmosGeoPoint":129,"geoPoint":134,"contacts":103},"Great Ormond Street Hospital NHS Foundation Trust","London","Greater London","WC1N 3JH","United Kingdom","UK",{"type":130,"coordinates":131},"Point",[132,133],-0.12574,51.50853,{"lat":133,"lon":132},{"type":136,"investigatorFullName":137,"investigatorTitle":138,"investigatorAffiliation":5,"oldNameTitle":103,"oldOrganization":103},"SPONSOR_INVESTIGATOR","Sebastiano Lava","Chief Investigator",[140,142,144],{"name":141,"class":6},"Great Ormond Street Hospital for Children NHS Foundation Trust",{"name":143,"class":6},"University College, London",{"name":5,"class":6},"100565535",false,"NCT06643442","Repurposing Empagliflozin for DMD-associated Cardiomyopathy in Children 6-18 Years of Age","Repurposing Empagliflozin for Duchenne Muscular Dystrophy - Associated Cardiomyopathy: a Pharmacokinetics, Safety and Proof-of-concept Study Among Children 6-18 Years of Age","REDMeD","Inclusion Criteria:\n\n* Children or adolescents 6 to 18 years of age with DMD-associated cardiomyopathy, followed either as in- or outpatients, will be eligible for inclusion.\n* Currently on heart failure medication (any drug or any combination).\n* Patients should potentially benefit from adding a SGLT2i (as judged by the treating physician and the PI or Co-PI).\n* Patients need to be on stable medical treatment, defined as no new heart failure drug started over the preceding 2 weeks and no major drug dose modification (apart minor adaptations, like weight adaptations, rounding or formulation changes) during the 2 weeks prior to enrolment.\n* Adolescents, respectively parents or caregivers of children, capable of giving informed consent.\n* Ability to tolerate a cardiac MRI investigation without the need of general anaesthesia.\n\nExclusion Criteria:\n\n* Inability to understand and go through the informed consent procedure.\n* Inability to receive medications per os or through a nasogastric tube.\n* Type 1 or Type 2 Diabetes mellitus or any underlying metabolic disease associated with hypoglycaemias.\n* Body weight \\\u003C15kg.\n* Current smokers (defined as \\>1 cigarette\u002Fweek).\n* Use of any other nicotine-delivering product (e.g. nicotine patches).\n* Any known illicit drug abuse.\n* Active chronic HBV, HCV or HIV.\n* Any major surgery within 4 weeks of first dose administration.\n* Blood transfusion recipient within 4 weeks of dose administration.\n* eGFR \\\u003C45mL\u002Fmin\u002F1.73m2 (simplified Schwartz formula or Filler formula).\n* K+ \\>6.5mmol\u002FL.\n* Blood glucose \\\u003C4mmol\u002FL.\n* There are no blood pressure exclusion criteria foreseen, but participants need to be haemodynamically stable, as assessed by the local investigator.\n* Sustained or symptomatic arrhythmia insufficiently controlled with drug and\u002For device therapy.\n* Cardio-surgical procedure within the 2 months prior to Visit 1, or interventional cardiac catheterization within 2 weeks prior to Visit 1, or the patient is planned to undergo cardiac surgery or an interventional cardiac catheterization during the study period (i.e. in the 6 months following Visit 1).\n* Post-menarchal female patients of childbearing potential cannot be included. Participants who begin menstruating during the trial will be discontinued from the IMP. However, their monitoring will continue up to 6 months after their first dose of IMP.\n* Known lactose intolerance, galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.\n* Known allergies to active ingredients or excipients of commercially available empagliflozin tablets.\n* Significant medical history of active severe medical disease.\n* Significant liver disease, Child Pugh Class C, or significant laboratory abnormalities at enrolment.\n* Significant gastroenterological or hepatic disease that could significantly impair absorption or metabolism of orally administered drugs.\n* Any medical co-morbidity, which is deemed incompatible (or only with relevant risk) with study participation by the treating clinician and\u002For the study investigator.\n* Active urinary tract infection (being treated with antibiotics at the moment of Visit 1) or other relevant bacterial infection, as judged by the treating clinician and\u002For the study investigator.\n* The patient is currently participating in another interventional clinical trial or has participated in such a trial during the \\\u003C14 days before Visit 1 (or if enrolment in this study is incompatible with the protocol of that preceding trial), or the duration of five half-lives of the IMP, whichever is longer.","ALL","6 Years","18 Years",{"count":156,"type":157},12,"ESTIMATED","INTERVENTIONAL",[160],"PHASE2","This study aims at exploring the use of empagliflozin in children and adolescents 6-18 years old with Duchenne muscular distrophy (DMD) - associated cardiomyopathy. This molecule is effective in reducing hospitalizations and mortality in adults with heart failure and is used in adolescents with type 2 diabetes mellitus, but little is known on children and adolescents with heart failure. Particularly, the best dose to use in this population is currently unknown. This trial aims to:\n\n1. define a dose rationale for this indication and age group (pharmacokinetic study),\n2. assess and monitor safety,\n3. assess ease-of-swallow,\n4. explore middle-term (3-6 months) efficacy and efficacy markers.\n\nParticipants will be asked to attend 5 study visits over 6 months, and one end-study visit 2-12 weeks thereafter. Visit 1 will entail an 8h day-hospital stay, while Visits 2, 3, 4 and 5, as well as the end-study visit, will be outpatient clinics (approximately 2h). Participants will be asked to take the studied drug once daily during the 6 months of the study period.\n\nNo comparison group is foreseen for this study.",[163],"DMD-associated Dilated Cardiomyopathy","NOT_YET_RECRUITING","2025-08-12",{"date":167,"type":168},"2025-08-15","ACTUAL",{"date":170,"type":157},"2025-10-01",{"date":172,"type":157},"2027-03-31",{"name":137,"class":6},1]