Palmitoylethanolamide/Luteolin Supplementation in Older Adults Undergoing Cardiac Surgery
26. juni 2026 opdateret af: Fondazione IRCCS San Gerardo dei Tintori
Palmitoylethanolamide/Luteolin for the Maintenance of Cognitive Performance in Older Adults Undergoing Cardiac Surgery
Postoperative Cognitive Dysfunction (POCD) is a common complication after surgery, particularly among older adults. It is characterized by cognitive impairment, reduced functional independence, and decreased quality of life. Growing evidence suggests that neuroinflammation plays a relevant role in POCD development and persistence.
Palmitoylethanolamide (PEA) is an endogenous lipid mediator involved in the regulation of neuroinflammatory processes through the modulation of non-neuronal cells, while luteolin is a flavonoid with well-known antioxidant properties. Under conditions of prolonged neuroinflammation, endogenous PEA levels may be insufficient to adequately counteract pro-inflammatory signaling, making exogenous administration necessary.
In this context, exogenous micronized and ultramicronized PEA (mPEA and umPEA) supplementation has been shown to modulate cognitive and executive functions, working memory, language, and activities of daily living. Moreover, the combination of umPEA and luteolin (PEALut) may produce synergistic effects by modulating neuroinflammation and supporting neuronal function.
This study aims to evaluate whether postoperative administration of co-ultramicronized PEA and luteolin (700 mg + 70 mg in 10 mL), added to standard of care, may contribute to the mitigation of POCD in older adults undergoing elective cardiac surgery, compared to standard care alone.
Studieoversigt
Status
Ikke rekrutterer endnu
Betingelser
Undersøgelsestype
Interventionel
Tilmelding (Anslået)
100
Fase
- Ikke anvendelig
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiekontakt
- Navn: Giuseppe Bellelli
- Telefonnummer: +39 039 233 3472
- E-mail: giuseppe.bellelli@unimib.it
Studiesteder
-
-
-
Monza, Italien
- Fondazione IRCCS San Gerardo dei Tintori
-
Kontakt:
- Clinical Office
- E-mail: ricerca.clinica@irccs-sangerardo.it
-
-
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
- Ældre voksen
Tager imod sunde frivillige
Ingen
Beskrivelse
Inclusion Criteria:
- Age ≥ 65 years
- Both genders
- Undergoing elective aortic or mitral valve replacement/reconstruction with or without coronary artery bypass grafting (CABG), at the Cardiac Surgery Unit of IRCCS San Gerardo dei Tintori Foundation (Monza, Italy)
- Prognosis quoad vitam ≥ 3 months
- Availability of a formal or informal caregiver who can assist the participant in taking the prescribed dose and following the visit schedule
- Any concomitant therapy should be stable
- Written informed consent obtained prior to randomization (from the participant or caregiver if the participant is unable to sign but clearly expresses the will to participate)
Exclusion Criteria:
- Severe dementia diagnosis
- Preoperative clinical diagnosis of delirium
- Other treatments/medications that may improve cognition
- Current treatment with m/umPEA or PEALut (Glialia®), or its use within 90 days prior to enrollment
- Contraindications to the use of PEALut, including allergy to excipients contained in the supplement and previous adverse reactions to PEALut
- Other clinical conditions or situations that could interfere with the study or prevent optimal participation, as judged by the researchers
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Støttende pleje
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: PEALut® + Standard of Care
Participants receive co-ultramicronized Palmitoylethanolamide + Luteolin (700 mg + 70 mg in 10 ml) in addition to Standard of Care
|
Standard for pleje
Oral suspension, 10 ml twice daily (every 12 hours), starting within 24 hours post-surgery and for 3 months, in add-on to the Standard of Care
Andre navne:
|
|
Aktiv komparator: Standard of Care
Participants receive only the Standard of Care
|
Standard for pleje
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Change in cognitive performance
Tidsramme: Baseline, hospital discharge (approximately postoperative day 7-10, depending on clinical course), 3 months after treatment, and 3 months after the end of treatment
|
Cognitive performance will be assessed using the Montreal Cognitive Assessment (MoCA), a 30-item screening tool that evaluates multiple cognitive domains, including memory, visuospatial ability, executive function, attention, language, and orientation.
Scores range from 0 to 30, with higher scores indicating better cognitive performance.
|
Baseline, hospital discharge (approximately postoperative day 7-10, depending on clinical course), 3 months after treatment, and 3 months after the end of treatment
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Incidence of Postoperative Cognitive Dysfunction (POCD)
Tidsramme: Hospital discharge (approximately postoperative day 7-10, depending on clinical course), and 3 months after treatment
|
Incidence of POCD will be defined as a decrease of at least 1 standard deviation from baseline MoCA score.
|
Hospital discharge (approximately postoperative day 7-10, depending on clinical course), and 3 months after treatment
|
|
Incidence, subtype and duration of postoperative delirium (POD)
Tidsramme: Daily, from 24 hours after the intervention until hospital discharge (approximately postoperative day 7-10, depending on clinical course)
|
Postoperative delirium will be assessed using the 4AT screening tool.
A score of ≥4 suggests possible delirium (with or without cognitive impairment), with higher scores indicating greater severity of cognitive disturbance.
Positive screenings will be confirmed using DSM-5 criteria.
Delirium subtype will be classified using the Delirium Motor Subtyping Scale-4 (DMSS-4), and duration will be recorded in days from onset to resolution.
|
Daily, from 24 hours after the intervention until hospital discharge (approximately postoperative day 7-10, depending on clinical course)
|
|
Change in Activities of Daily Living (ADL)
Tidsramme: Baseline, 3 months after treatment, and 3 months after the end of treatment
|
Activities of daily living will be assessed using the six-item Katz Activities of Daily Living (ADL) Index.
Scores range from 0 to 6, with higher values indicating greater function.
|
Baseline, 3 months after treatment, and 3 months after the end of treatment
|
|
Change in Instrumental Activities of Daily Living (IADL)
Tidsramme: Baseline, 3 months after treatment, and 3 months after the end of treatment
|
Functional status will be assessed using the Instrumental Activities of Daily Living (IADL) scale.
Scores range from 0 to 8, with higher scores indicating better functional ability.
|
Baseline, 3 months after treatment, and 3 months after the end of treatment
|
|
Change in Short Physical Performance Battery (SPPB)
Tidsramme: Baseline, 3 months after treatment, and 3 months after the end of treatment
|
Physical performance will be assessed using the Short Physical Performance Battery (SPPB), which evaluates balance, gait speed, and chair stand performance.
Scores range from 0 to 12, with higher scores indicating better physical performance.
|
Baseline, 3 months after treatment, and 3 months after the end of treatment
|
|
Change in Handgrip Strength
Tidsramme: Baseline, 3 months after treatment, and 3 months after the end of treatment
|
Muscle strength will be assessed using a handgrip dynamometer.
Handgrip strength will be recorded in kilograms (kg), with higher values indicating greater muscle strength.
|
Baseline, 3 months after treatment, and 3 months after the end of treatment
|
|
Rehospitalization
Tidsramme: From 24 hours after the intervention to 6 months after randomization
|
Incidence of rehospitalization
|
From 24 hours after the intervention to 6 months after randomization
|
|
Mortality
Tidsramme: From 24 hours after the intervention to 6 months after randomization
|
Incidence of mortality
|
From 24 hours after the intervention to 6 months after randomization
|
|
Incidence of Treatment-Related Adverse Events
Tidsramme: From first treatment administration up to 3 months after the end of treatment
|
Safety and Adherence assessment will be assessed by monitoring the incidence and severity of adverse events occurring during the study period.
|
From first treatment administration up to 3 months after the end of treatment
|
|
Plasma p-tau217 levels
Tidsramme: Baseline
|
Plasma levels of phosphorylated tau (p-tau217) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline
|
|
Plasma Aβ42 levels
Tidsramme: Baseline
|
Plasma levels of Amyloid beta 42 (Aβ42) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline
|
|
Change in plasma IL-6 levels
Tidsramme: Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Plasma levels of Interleukin-6 (IL-6) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
|
Change in plasma s-RAGE levels
Tidsramme: Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Plasma levels of soluble Receptor for Advanced Glycation End-products (s-RAGE) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
|
Change in plasma GDF-15 levels
Tidsramme: Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Plasma levels of Growth Differentiation Factor-15 (GDF-15) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
|
Change in plasma GFAP levels
Tidsramme: Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Plasma levels of Glial Fibrillary Acidic Protein (GFAP) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
|
Change in plasma NSE levels
Tidsramme: Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Plasma levels of Neuron-Specific Enolase (NSE) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
|
Change in plasma NfL levels
Tidsramme: Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Plasma levels of Neurofilament Light Chain (NfL) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
|
Change in plasma FGF-1 levels
Tidsramme: Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Plasma levels of Fibroblast Growth Factor-1 (FGF-1) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
|
Change in plasma BDNF levels
Tidsramme: Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Plasma levels of Brain-Derived Neurotrophic Factor (BDNF) will be measured in blood samples using standard clinical laboratory assays.
|
Baseline, Immediately after surgery (within 24 hours, before PEALut administration), and 3 months after treatment
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Efterforskere
- Ledende efterforsker: Giuseppe Bellelli, School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Generelle publikationer
- Clayton P, Hill M, Bogoda N, Subah S, Venkatesh R. Palmitoylethanolamide: A Natural Compound for Health Management. Int J Mol Sci. 2021 May 18;22(10):5305. doi: 10.3390/ijms22105305.
- Suraarunsumrit P, Srinonprasert V, Kongmalai T, Suratewat S, Chaikledkaew U, Rattanasiri S, McKay G, Attia J, Thakkinstian A. Outcomes associated with postoperative cognitive dysfunction: a systematic review and meta-analysis. Age Ageing. 2024 Jul 2;53(7):afae160. doi: 10.1093/ageing/afae160.
- Moller JT, Cluitmans P, Rasmussen LS, Houx P, Rasmussen H, Canet J, Rabbitt P, Jolles J, Larsen K, Hanning CD, Langeron O, Johnson T, Lauven PM, Kristensen PA, Biedler A, van Beem H, Fraidakis O, Silverstein JH, Beneken JE, Gravenstein JS. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 Mar 21;351(9106):857-61. doi: 10.1016/s0140-6736(97)07382-0.
- Savageau JA, Stanton BA, Jenkins CD, Frater RW. Neuropsychological dysfunction following elective cardiac operation. II. A six-month reassessment. J Thorac Cardiovasc Surg. 1982 Oct;84(4):595-600.
- Zhang L, Qiu Y, Zhang ZF, Zhao YF, Ding YM. Current perspectives on postoperative cognitive dysfunction in geriatric patients: insights from clinical practice. Front Med (Lausanne). 2024 Sep 27;11:1466681. doi: 10.3389/fmed.2024.1466681. eCollection 2024.
- Nobili S, Micheli L, Lucarini E, Toti A, Ghelardini C, Di Cesare Mannelli L. Ultramicronized N-palmitoylethanolamine associated with analgesics: Effects against persistent pain. Pharmacol Ther. 2024 Jun;258:108649. doi: 10.1016/j.pharmthera.2024.108649. Epub 2024 Apr 12.
- Colizzi M, Bortoletto R, Colli C, Bonomo E, Pagliaro D, Maso E, Di Gennaro G, Balestrieri M. Therapeutic effect of palmitoylethanolamide in cognitive decline: A systematic review and preliminary meta-analysis of preclinical and clinical evidence. Front Psychiatry. 2022 Oct 28;13:1038122. doi: 10.3389/fpsyt.2022.1038122. eCollection 2022.
- Caltagirone C, Cisari C, Schievano C, Di Paola R, Cordaro M, Bruschetta G, Esposito E, Cuzzocrea S; Stroke Study Group. Co-ultramicronized Palmitoylethanolamide/Luteolin in the Treatment of Cerebral Ischemia: from Rodent to Man. Transl Stroke Res. 2016 Feb;7(1):54-69. doi: 10.1007/s12975-015-0440-8. Epub 2015 Dec 26.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart (Anslået)
1. juni 2026
Primær færdiggørelse (Anslået)
1. juni 2027
Studieafslutning (Anslået)
1. juni 2028
Datoer for studieregistrering
Først indsendt
11. juni 2026
Først indsendt, der opfyldte QC-kriterier
26. juni 2026
Først opslået (Faktiske)
2. juli 2026
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
2. juli 2026
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
26. juni 2026
Sidst verificeret
1. maj 2026
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
- Sygdomme i nervesystemet
- Psykiske lidelser
- Postoperative komplikationer
- Patologiske processer
- Neurokognitive lidelser
- Betændelse
- Kognitionsforstyrrelser
- Patologiske tilstande, tegn og symptomer
- Postoperative kognitive komplikationer
- Neuroinflammatoriske sygdomme
- Kognitiv dysfunktion
- Sundhedstjenester Administration
- Sundhedsvæsenets kvalitet, adgang og evaluering
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ring
- Pyraner
- Sundhedskvalitet
- Kvalitetsindikatorer, sundhedsvæsenet
- Benzopyrans
- Flavonoider
- Kromoner
- Flavoner
- Standard for pleje
- Luteolin
Andre undersøgelses-id-numre
- PEGASUS COG
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
INGEN
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Ingen
Studerer et amerikansk FDA-reguleret enhedsprodukt
Ingen
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .