{"type":"trials","record":{"id":21644,"source_id":"clinicaltrials-gov","external_id":"NCT04928963","title":"Fighting Immunosenescence and Promoting Immunity by a Fasting-mimicking Diet Elderly.","brief_summary":"Background: Immunosenescence is an aging-dependent phenomenon underlying age dependent deterioration in the function of the immune system, characterized by a decline in B and T cells with a relative increase in natural killer (NK) cells. Aging also promotes chronic inflammation accompanied by increased levels of pro-inflammatory cytokines. Both immunosenescence and inflammation contribute to frailty, which is a geriatric syndrome characterized by age-related deterioration in multiple physiological systems resulting in greater vulnerability to stressors and increased risk of poor outcomes including longer hospital stays, postoperative complications, poor responses to vaccination, functional decline, and death. Although pharmacological interventions could be developed to address immunosenescence, inflammation and frailty, a dietary intervention that does not cause weight or muscle loss may be a preferable option, particularly if it is periodic in nature and it only needs to be adopted for a few weeks per year. Hypothesis: We will test the hypothesis that a newly formulated and relatively high calorie fasting mimicking diet (FMD) to be administered to subjects age 65-80 once a month for 5 days for two to six cycles can partially reverse immunosenescence and inflammation, thus contributing to the reduction of frailty. Aims: This proposal is divided into 2 main tasks: Task 1: We will determine whether FMD cycles in mice: a) prevent frailty syndrome onset and symptoms B) delay or reverse age-related immunosenescence and inflammaging, C) improve the functionality of bone marrow cells, D) enhances the response to flu vaccination. Task 2: A )We will develop a special relatively high calorie FMD medical food for testing in humans, B) We will test the safety and efficacy of the FMD medical food in an aged and frail individuals (65-80 yr) for 2-5 day cycles preceding their annual influenza vaccination. Expected results: In mice, we expect that the FMD diet will reduce the clinical signs of frailty during aging, and in particular increase immune system influenza vaccine response by preventing immunesenescence. We expect that the FMD will reduce phosphorylation of mTOR and of its downstream targets, and induce autophagy and apoptosis in WBCs. These effects are anticipated to remove damaged cells and promote the activation of hematopoietic stem cells and the generation of new WBCs. We also expect that the transient increase in corticosteroids and removal of damage immune cells will be accompanied by a decrease in systemic inflammation. Increased performance on rotarod and other measures of frailty is also anticipated. In humans, we expect that the FMD will be well tolerated by the pre-frail elderly without major adverse events and that it will be possible to achieve high compliance to this diet. We also anticipate that elderly undergoing the FMD protocol followed by 30 days of a normal diet plus supplements will exhibit better functional status and better resp…","overall_status":"Unknown","phases":["PHASE1","PHASE2"],"study_type":"INTERVENTIONAL","sponsor":"University of Genova","enrollment":40,"countries":["Italy"],"start_date":"2020-09-15","completion_date":"2022-12-01","last_update_date":"2021-10-25","source_url":"https://clinicaltrials.gov/study/NCT04928963","editorial_summary":"A registered PHASE1, PHASE2 study indexed because it matched monitored longevity research terms. Registry status: Unknown. Registration does not establish safety or effectiveness.","first_seen_at":"2026-09-24T01:17:08.26846+00:00","last_seen_at":"2026-09-25T06:15:06.064+00:00","metadata":{"sex":"ALL","acronym":null,"age_range":"65 Years to 80 Years","comparator":"Placebo diet","organization":"University of Genova","interventions":["Prolon - FMD"],"registry_source":"ClinicalTrials.gov","outcome_measures":["Safety of FMD in terms of percentage of patients experiencing adverse events and/or worsening of nutritional status — 6…","Feasibility of FMD in terms of percentage of patients able to complete the diet regimen — 6 months","Efficacy of FMD in terms of immune response after Flu vaccine — 1 month","Efficacy of FMD in terms of prevention of frailty — 6 months"],"design_description":"RANDOMIZED · PARALLEL · TREATMENT · SINGLE","source_has_results":false},"controlled_terms":["Frailty","Inflammation","Immune System Disorder","Prolon - FMD"],"relevance_confidence":100,"source_quality_score":100,"freshness_score":50,"publication_state":"published","match_explanation":"Title contains controlled term: immunosenescence.","quality_checked_at":"2026-09-25T06:15:09.632521+00:00","duplicate_cluster_key":"id:nct04928963","duplicate_of_id":null,"evidence_snapshot":{"status":"structured","version":1,"duration":"2020-09-15 to 2022-12-01","comparator":"Placebo diet","confidence":"structured-source","population":"ALL · 65 Years to 80 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":"2026-09-25T06:15:06.090Z","intervention":["Prolon - FMD"],"participants":40,"study_design":"RANDOMIZED · PARALLEL · TREATMENT · SINGLE","subject_scope":"Human clinical study registration","evidence_stage":"PHASE1, PHASE2","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":["Safety of FMD in terms of percentage of patients experiencing adverse events and/or worsening of nutritional status — 6…","Feasibility of FMD in terms of percentage of patients able to complete the diet regimen — 6 months","Efficacy of FMD in terms of immune response after Flu vaccine — 1 month","Efficacy of FMD in terms of prevention of frailty — 6 months"],"regulatory_context":"Trial registration is not regulatory approval and does not establish that an intervention is available."},"clinical_trial_topics":[{"topic_slug":"immune-aging","is_published":true,"match_reasons":["Title contains controlled term: immunosenescence.","Abstract contains controlled term: immunosenescence.","Title supplies longevity context: senescence, elderly.","Study type is explicitly identified as INTERVENTIONAL."],"matched_fields":["title","abstract","title context","study type"],"relevance_score":100,"intelligence_topics":{"name":"Immune ageing","slug":"immune-aging"}}],"content_sources":{"name":"ClinicalTrials.gov","homepage_url":"https://clinicaltrials.gov/"}},"canonical_url":"https://www.immortal.life/trials/21644","automation_disclosure":"Generated automatically from cited source metadata. No scientist, clinician, researcher, editor, or human reviewer evaluates this publication before release."}