grant

A pilot trial of skin barrier restoration to reduce systemic inflammation

Organization UNIVERSITY OF CALIFORNIA, SAN FRANCISCOLocation SAN FRANCISCO, UNITED STATESPosted 1 Apr 2024Deadline 31 Mar 2027
NIHUS FederalResearch GrantFY2025(TNF)-αAcuteAddressAffectAgeAge YearsAgingAllergensAnimalsAreaAttentionB cell differentiation factorB cell stimulating factor 2B-Cell Differentiation FactorB-Cell Differentiation Factor-2B-Cell Stimulatory Factor-2BCDFBNP Gene ProductBNP-32BSF-2BSF2BlindedBlood SerumBrain Natriuretic Peptide-32Brain natriuretic peptideC-reactive proteinCachectinCeramidesCessation of lifeChinaChronicClinicalConsensusCoriumCreamCutisDataDeathDefense MechanismsDermisDrynessEffectivenessElectrical ImpedanceEnvironmental ExposureEquilibriumFutureGeroscienceHPGFHepatocyte-Stimulating FactorHumanHybridoma Growth FactorHydrationHydration statusHydrogen OxideIFN-beta 2IFNB2IL-6IL6 ProteinImmuneImmunesImmunomodulationImpedanceIndividualInflammagingInflammationInflammatoryInterleukin-6InterleukinsInterventionInvestigatorsLinkLipidsMGI-2Macrophage-Derived TNFMainland ChinaMeasuresMiceMice MammalsModern ManMonocyte-Derived TNFMorbidityMorbidity - disease rateMurineMusMyeloid Differentiation-Inducing ProteinNatriuretic Factor-32NesiritideOintmentsOrganOutcomeParaffin JellyParticipantPenetrancePermeabilityPetrolatumPetroleum JellyPilot ProjectsPlacebosPlasmacytoma Growth FactorProcessProteins, specific or class, C-reactiveProtocolProtocols documentationPublic HealthRandomizedResearchResearch PersonnelResearchersResistanceRiskRoleSalvesSenilitySerumSham TreatmentSkinSourceSterilitySurfaceTNFTNF ATNF AlphaTNF geneTNF-αTNFATNFαToxinTreatment PeriodTumor Necrosis FactorTumor Necrosis Factor-alphaType-B Natriuretic PeptideUnguentsWateracceptability and feasibilityage associatedage associated declineage correlatedage dependentage dependent declineage linkedage relatedage related declineage reversalage specificage-related inflammationaged miceaged mouseagesaging associated inflammationaging reversalalleviate age relatedalleviate agingameliorating agingbalancebalance functionbrain Natriuretic factorcommensal floracommensal microbescommensal microbiotacommensal microfloracommunity microbescommunity settingcost effectivecounter age relatedcounter agingcounteract age relatedcounteract agingcutaneous barriercutaneous microbiomedata integritydecline with agedermal barrierdermal microbiomedesigndesigningefficacy trialelderly miceelectric impedanceepidermal barrierepidermal microbiomefrailtygeroscientificimmune modulationimmune regulationimmunologic reactivity controlimmunomodulatoryimmunoregulationimmunoregulatoryimprovedinflamm-ageinginflamm-aginginflammation associated with aginginflammation markerinflammatory markerinnovateinnovationinnovativeinterferon beta 2microbe communitymicrobe pathogenmicrobialmicrobial communitymicrobial pathogenmicroorganism communitymortalitymultimorbiditymultiple chronic conditionsnatural agingnormal agingnormative agingold miceolder adultolder adulthoodpathogenpathogenic microbepharmacologicpilot studypilot trialpolymicrobial communityprematureprematuritypsychological defense mechanismrandomisationrandomizationrandomly assignedrecruitrepairrepairedresistantresponserestorationretention rateretention strategyreverse agereverse agingreverse aging effectsreversible agingsham therapyskin barrierskin biomeskin microbiomesocial rolesterilesystemic inflammationsystemic inflammatory responsetooltreatment daystreatment durationtrial design
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Full Description

PROJECT SUMMARY
A chronic inflammatory state, termed inflammageing, is a major driver of morbidity and premature death among

older adults. Although the identification of inflammatory triggers has been identified as a critical area for aging

research, little attention has focused on the skin, despite its role as a primary immunoregulatory organ. Normal

aging is associated with increased skin barrier permeability, which leads to subclinical inflammatory cascades

in the skin and serum. We hypothesize that age-associated decline of skin barrier function contributes to

inflammageing and that restoring the skin barrier with moisturizers will reduce systemic inflammation.

We propose a pilot trial designed to determine the best measures of skin barrier function in older adults, the

most sensitive measures of systemic inflammation, the role of the cutaneous microbiome, and the feasibility

and acceptability of moisturizer use. In a parallel, 8-week, self-controlled design, 32 subjects ≥70 years of age

will be randomized to treatment with a ceramide moisturizing cream or petrolatum ointment. Changes in

inflammatory markers, skin barrier function, and microbial diversity will be compared between a 4-week

treatment period of moisturizer application and a 4-week placebo period. We will also examine recruitment

efficacy, retention rates, fidelity to the treatment, data integrity, and the acceptability of the intervention and

protocol. The results will be used to design a future randomized efficacy trial of moisturizers to reduce systemic

inflammation. While many other pharmacologic strategies for reducing inflammation in older adults are

considered too risky or expensive for widespread use, moisturizers are a promising intervention that is safe

and accessible in diverse community settings.

Grant Number: 5R21AR082620-02
NIH Institute/Center: NIH

Principal Investigator: Katrina Abuabara

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