[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657182":3},{"organization":4,"outcomesModule":7,"designInfo":14,"detailedDescription":17,"studyPopulation":18,"armGroups":13,"interventions":13,"overallOfficials":13,"centralContacts":19,"locations":25,"responsibleParty":39,"collaborators":13,"id":43,"slug":44,"hasResults":45,"nctId":46,"briefTitle":47,"officialTitle":48,"acronym":49,"eligibilityCriteria":50,"healthyVolunteers":45,"sex":51,"minAge":13,"maxAge":13,"enrollmentInfo":52,"targetDuration":13,"studyType":55,"phases":13,"briefSummary":56,"conditions":57,"keywords":59,"overallStatus":28,"whyStopped":13,"lastUpdateSubmitDate":65,"lastUpdatePostDateStruct":66,"startDateStruct":69,"completionDateStruct":71,"leadSponsor":73,"locationsCount":74},{"fullName":5,"class":6},"Azienda Ospedaliero Universitaria Maggiore della Carita","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":13},[9],{"measure":10,"description":11,"timeFrame":12},"Circulating Hepatokine Levels","Measurement of circulating hepatokines, including TMPRSS6, in serum and plasma using immunoenzymatic assays such as ELISA or multiplex assays, and assessment of their association with clinical and biochemical parameters related to glucose metabolism, lipid metabolism, and liver health.","At study enrollment",null,{"allocation":13,"interventionModel":13,"interventionModelDescription":13,"primaryPurpose":13,"observationalModel":15,"timePerspective":16,"maskingInfo":13},"COHORT","PROSPECTIVE","Leptin receptor deficiency (LEPRD) is an extremely rare autosomal recessive endocrine disorder characterized by severe early-onset obesity, hyperphagia, and metabolic abnormalities resulting from impaired leptin signaling. Genetic forms of lipodystrophy, including generalized and partial lipodystrophy, may also be associated with severe leptin deficiency and impaired leptin signaling, leading to abnormalities in glucose and lipid metabolism and ectopic fat accumulation, particularly in the liver.\n\nCurrent therapeutic approaches do not fully address the metabolic complications associated with these rare disorders. In patients with LEPRD, setmelanotide, a selective melanocortin-4 receptor (MC4R) agonist, acts downstream of the leptin-melanocortin pathway and can substantially reduce hunger and body weight. However, the response to treatment may be limited in some patients, and metabolic and hepatic abnormalities may persist. Similarly, metreleptin replacement therapy used in selected forms of genetic lipodystrophy may not completely correct all metabolic and hepatic abnormalities. Therefore, identification of additional molecular pathways involved in the metabolic complications of these conditions is needed.\n\nTMPRSS6 is a type II transmembrane serine protease predominantly expressed in hepatocytes. It negatively regulates hepatic BMP-SMAD signaling by cleaving hemojuvelin (HJV), a coreceptor of the BMP pathway, thereby contributing to the regulation of hepcidin production. Preclinical studies have shown that genetic inactivation or antisense oligonucleotide-mediated silencing of Tmprss6 in mice results in activation of the hepatic BMP-SMAD pathway and is associated with beneficial metabolic effects, including improved glucose metabolism, reduced adipose tissue accumulation, and attenuation of inflammation.\n\nPreliminary studies in murine models have identified circulating liver-derived factors, including TMPRSS6-related molecular markers, that may be involved in the metabolic alterations associated with impaired leptin signaling. These findings suggest that TMPRSS6 and the hepatic BMP-SMAD pathway may play a role in the interaction between hepatic function and systemic glucose and lipid metabolism.\n\nThe present pilot observational study is designed to investigate whether molecular alterations identified in preclinical models are also detectable in humans with LEPRD or genetic lipodystrophy associated with leptin deficiency. Blood samples will be collected to measure circulating TMPRSS6 and other molecular or metabolic markers previously identified in preclinical studies as being regulated by or associated with TMPRSS6 activity.\n\nThe study will integrate these molecular findings with available clinical and biochemical characteristics of the participants. Particular attention will be given to markers of glucose and lipid metabolism and hepatic involvement, in order to explore potential associations between TMPRSS6-related markers and the metabolic phenotype of these rare disorders.\n\nThe study is intended to provide preliminary evidence regarding the relevance of the TMPRSS6-related pathway in humans. Identification of a specific circulating molecular signature associated with TMPRSS6 may improve understanding of the mechanisms underlying metabolic and hepatic complications in LEPRD and genetic lipodystrophy and provide a rationale for future translational studies investigating this pathway as a potential therapeutic target.","The study population will include pediatric and adult patients of both sexes with leptin receptor deficiency (LEPRD) or genetically determined leptin deficiency associated with generalized or partial lipodystrophy. Approximately 35 patients with genetic lipodystrophy and up to 10 patients with LEPRD will be enrolled. Participants may be untreated or receiving setmelanotide or metreleptin.",[20],{"name":21,"role":22,"phone":23,"phoneExt":13,"email":24},"Flavia Prodam, MD, PhD","CONTACT","+39-0321-660693","flavia.prodam@med.uniupo.it",[26],{"facility":27,"status":28,"city":29,"state":30,"zip":31,"country":30,"countryCode":32,"cosmosGeoPoint":33,"geoPoint":38,"contacts":13},"AOU Maggiore della Carità - SCDU Endocrinology","RECRUITING","Novara","Italy","28100","IT",{"type":34,"coordinates":35},"Point",[36,37],8.62118,45.44694,{"lat":37,"lon":36},{"type":40,"investigatorFullName":41,"investigatorTitle":42,"investigatorAffiliation":5,"oldNameTitle":13,"oldOrganization":13},"PRINCIPAL_INVESTIGATOR","Flavia Prodam","Associate Professor","100657182","targeting-the-hepatic-bmp-smad-pathway-in-leptin-receptor-deficiency-leprd-100657182",false,"NCT07833592","Targeting the Hepatic BMP-SMAD Pathway in Leptin Receptor Deficiency (LEPRD)","Targeting the Hepatic BMP-SMAD Pathway in Leptin Receptor Deficiency (LEPRD): A New Strategy for Treating Severe Genetic Obesity or Leptin Deficiency","THOLD","Inclusion Criteria:\n\n* Male or female participants aged 0 to 99 years.\n* Diagnosis of leptin receptor deficiency (LEPRD) or genetically determined leptin deficiency associated with generalized or partial lipodystrophy.\n* Participants may be untreated or receiving treatment with setmelanotide or metreleptin.\n* Ability and willingness to provide written informed consent. For participants under the legal age, informed consent will be obtained from the parent(s) or legal guardian(s), together with assent from the minor when appropriate.\n\nExclusion Criteria:\n\n* Diagnosis of another form of genetic obesity.\n* Pregnancy or planned pregnancy during the study participation period.\n* Liver disease or hepatic impairment attributable to other causes, including excessive alcohol consumption.\n* Genetically determined dyslipidemia due to another cause.","ALL",{"count":53,"type":54},35,"ESTIMATED","OBSERVATIONAL","The goal of this observational study is to learn more about the role of TMPRSS6 in patients with leptin receptor deficiency (LEPRD) or genetic lipodystrophy associated with leptin deficiency. LEPRD is a rare genetic condition that causes severe obesity and excessive hunger, while genetic lipodystrophy is characterized by a loss of body fat and can be associated with severe metabolic problems.\n\nThe main questions it aims to answer are:\n\nIs TMPRSS6 associated with metabolic and liver health in patients with LEPRD or genetic lipodystrophy? Are differences in TMPRSS6 levels or activity associated with blood sugar control, lipid levels, body fat, or liver health?\n\nParticipants will:\n\nProvide a blood sample for the measurement of TMPRSS6 and other metabolic and molecular markers.\n\nHave information from their clinical and laboratory assessments collected for the study.\n\nThis study may help researchers better understand the mechanisms underlying metabolic complications in LEPRD and genetic lipodystrophy and may contribute to the identification of new potential therapeutic targets in the future.",[58],"Leptin Receptor Deficiency Obesity",[60,61,62,63,64],"Leptin receptor deficiency (LEPRD)","TMPRSS6","BMP-SMAD signaling","Glucose metabolism","Lipid metabolism","2026-09-17",{"date":67,"type":68},"2026-09-22","ACTUAL",{"date":70,"type":54},"2026-09-10",{"date":72,"type":54},"2029-09",{"name":5,"class":6},1]