Palmitoylethanolamide/Luteolin Supplementation in Older Adults Undergoing Cardiac Surgery

NCT07681063 | Not Yet Recruiting

• 1 other identifier: PEGASUS COG
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Postoperative Cognitive Dysfunction

Keywords

Neuroinflammation; Palmitoylethanolamide; Luteolin; Postoperative Cognitive Dysfunction; Cardiac Surgery; Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Change in cognitive performance

  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

Secondary Outcomes (19)

• Incidence of Postoperative Cognitive Dysfunction (POCD)

  Hospital discharge (approximately postoperative day 7-10, depending on clinical course), and 3 months after treatment

• Incidence, subtype and duration of postoperative delirium (POD)

  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)

  Baseline, 3 months after treatment, and 3 months after the end of treatment

• Change in Instrumental Activities of Daily Living (IADL)

  Baseline, 3 months after treatment, and 3 months after the end of treatment

• Change in Short Physical Performance Battery (SPPB)

  Baseline, 3 months after treatment, and 3 months after the end of treatment

Study Arms (2)

PEALut® + Standard of Care

EXPERIMENTAL

Participants receive co-ultramicronized Palmitoylethanolamide + Luteolin (700 mg + 70 mg in 10 ml) in addition to Standard of Care

Dietary Supplement: co-ultramicronized Palmitoylethanolamide + Luteolin (700 mg + 70 mg in 10 ml); Other: Standard of Care

Standard of Care

ACTIVE COMPARATOR

Participants receive only the Standard of Care

Other: Standard of Care

Interventions

co-ultramicronized Palmitoylethanolamide + Luteolin (700 mg + 70 mg in 10 ml) DIETARY_SUPPLEMENT

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

Also known as: Glialia® oral suspension, PEALut® oral suspension

PEALut® + Standard of Care

Standard of Care OTHER

Standard of Care

PEALut® + Standard of Care; Standard of Care

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fondazione IRCCS San Gerardo dei Tintori: lead

Study Sites (1)

Fondazione IRCCS San Gerardo dei Tintori

Monza, Italy

Location

Related Publications (8)

• 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.

  PMID: 6981735 BACKGROUND

• 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.

  PMID: 9525362 BACKGROUND

• 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.

  PMID: 39058915 BACKGROUND

• 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.

  PMID: 39399113 BACKGROUND

• 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.

  PMID: 38615798 BACKGROUND

• 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.

  PMID: 34069940 BACKGROUND

• 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.

  PMID: 36387000 BACKGROUND

• 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.

  PMID: 26706245 BACKGROUND

MeSH Terms

Conditions

Postoperative Cognitive Complications; Neuroinflammatory Diseases; Cognitive Dysfunction

Interventions

Luteolin; Standard of Care

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Nervous System Diseases; Inflammation

Intervention Hierarchy (Ancestors)

Flavones; Flavonoids; Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Giuseppe Bellelli

  School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giuseppe Bellelli

CONTACT

+39 039 233 3472; giuseppe.bellelli@unimib.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2026
• First Posted: July 2, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: July 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)