{"type":"trials","record":{"id":22679,"source_id":"clinicaltrials-gov","external_id":"NCT03907553","title":"Aging of Hematopoietic Stem Cells - Molecular Architecture of Marrow Dysplasia and Clinical Contribution of Ineffective Hematopoiesis to Frailty in the Elderly","brief_summary":"The prevalence and incidence of anemia tend to increase with advancing age. Relatively low hemoglobin concentrations are a common laboratory finding in the elderly, for the most part judged by physicians as a sign without clinical relevance or as a marker of an underlying chronic disease having no independent influence on health. In recent years several studies have started to challenge the widespread and self-perpetuating perception of anemia as an innocent bystander, reporting worse cognitive and quality of life outcomes and increased risk of hospitalization and mortality in the general population. Focusing on elderly people, anemia has a clear association with the phenotypic features of frailty syndrome affecting 3-5% of individuals of 65-70 years of age and, more importantly 30% of those aged 85 years or older. Among frail older adults, anemia is a powerful prognostic factor for the development of frailty-related problems such as muscle weakness, reduced performance, falls, and mortality. Nutrient deficiency, chronic inflammation and renal insufficiency account for the large majority of cases of anemia in the elderly, while underlying cause remained unexplained in 25% of the cases. Preliminary evidence indicates that a significant proportion of ''unexplained anemia'' may account for myelodysplasia(MDS). MDS is a condition typically occurring in elderly people, characterized by clonal proliferation of hematopoietic stem cells (HSC), which partly retain their capacity to differentiate and maturate, but do so in an inefficient manner (ineffective hematopoiesis). Anemia represents the most important prognostic factor in MDS. With time a portion of patients evolve into overt myeloid malignancy (i.e., acute leukemia). Somatic mutations occur in the genomes of healthy HSC at a low, but detectable frequency during normal DNA replication. Although most mutations are rapidly corrected by DNA repair mechanisms, those that persist are propagated during HSC self-renewal. Some evidence suggest that these early driver mutations dictate future trajectories of evolution with distinct clinical phenotypes. There has been much excitement in the research community about the translational opportunities offered by genome sequencing, possibly leading to the identification of specific types of mutational processes of how genome interact with environmental factors in determining clinical conditions associated with aging and to the implementation of a personalized molecular diagnosis and treatment for every patient. In this translational research project, using an integrated genomic analysis based on next generation sequencing (NGS) technologies,the investigators plan to dissect the genomic architecture of MDS, significantly contributing to many features of frailty and to individual vulnerability. The investigators will perform mutation analysis of candidate genes in a large and well characterized cohort of individuals belonging to the \"Health and Anemia'' study. \"Hea…","overall_status":"Completed","phases":[],"study_type":"OBSERVATIONAL","sponsor":"Istituto Clinico Humanitas","enrollment":5000,"countries":["Italy"],"start_date":"2003-07-01","completion_date":null,"last_update_date":"2019-04-22","source_url":"https://clinicaltrials.gov/study/NCT03907553","editorial_summary":"A registered study indexed because it matched monitored longevity research terms. Registry status: Completed. Registration does not establish safety or effectiveness.","first_seen_at":"2026-09-24T03:17:05.484536+00:00","last_seen_at":"2026-09-25T06:15:18.072+00:00","metadata":{"sex":"ALL","acronym":null,"age_range":"65 Years","comparator":null,"organization":"Istituto Clinico Humanitas","interventions":["targeted genome sequencing"],"registry_source":"ClinicalTrials.gov","outcome_measures":["genotype-phenotype correlation — 2016-2019"],"design_description":null,"source_has_results":false},"controlled_terms":["Anemia","Clonal Hematopoiesis","targeted genome sequencing"],"relevance_confidence":100,"source_quality_score":100,"freshness_score":50,"publication_state":"published","match_explanation":"Title contains controlled term: stem cell.","quality_checked_at":"2026-09-25T06:15:18.821558+00:00","duplicate_cluster_key":"id:nct03907553","duplicate_of_id":null,"evidence_snapshot":{"status":"structured","version":1,"duration":"From 2003-07-01","comparator":null,"confidence":"structured-source","population":"ALL · 65 Years","provenance":{"duration":"start_date and completion_date","comparator":"registry arm fields","population":"registry eligibility fields","intervention":"registry intervention fields","participants":"enrollment","study_design":"study_type and registry design fields","evidence_stage":"phases","reported_outcome":"not available","outcomes_measured":"registry outcome-measure fields"},"generated_at":"2026-09-25T06:15:18.091Z","intervention":["targeted genome sequencing"],"participants":5000,"study_design":"OBSERVATIONAL","subject_scope":"Human clinical study registration","evidence_stage":"Phase not reported","safety_context":"Eligibility, adverse-event details, and clinical decisions must be checked in the official registry and with qualified clinicians.","source_support":"Structured registry protocol metadata; no finding-level conclusion is generated.","main_limitation":"This is a study registration. No reusable structured result is available here, so it cannot show whether the intervention worked or was safe.","reported_outcome":null,"outcomes_measured":["genotype-phenotype correlation — 2016-2019"],"regulatory_context":"Trial registration is not regulatory approval and does not establish that an intervention is available."},"clinical_trial_topics":[{"topic_slug":"stem-cells","is_published":true,"match_reasons":["Title contains controlled term: stem cell.","Abstract contains controlled term: stem cell.","Title supplies longevity context: aging, frailty.","Study type is explicitly identified as OBSERVATIONAL."],"matched_fields":["title","abstract","title context","study type"],"relevance_score":100,"intelligence_topics":{"name":"Stem cells","slug":"stem-cells"}}],"content_sources":{"name":"ClinicalTrials.gov","homepage_url":"https://clinicaltrials.gov/"}},"canonical_url":"https://www.immortal.life/trials/22679","automation_disclosure":"Generated automatically from cited source metadata. No scientist, clinician, researcher, editor, or human reviewer evaluates this publication before release."}