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NCT Number: NCT07681063

Palmitoylethanolamide/Luteolin Supplementation 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.

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Key information

Conditions

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

Age range

65 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Fondazione IRCCS San Gerardo dei Tintori

Monza, Italy

Location contact

Clinical Office

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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

Other names: Glialia® oral suspension, PEALut® oral suspension

Standard of care

Other

Standard of Care

Primary outcomes

  1. Change in cognitive performance

    Time frame: 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.

Secondary outcomes

  1. Incidence of Postoperative Cognitive Dysfunction (POCD)

    Time frame: 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.

  2. Incidence, subtype and duration of postoperative delirium (POD)

    Time frame: 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.

  3. Change in Activities of Daily Living (ADL)

    Time frame: 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.

  4. Change in Instrumental Activities of Daily Living (IADL)

    Time frame: 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.

  5. Change in Short Physical Performance Battery (SPPB)

    Time frame: 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.

  6. Change in Handgrip Strength

    Time frame: 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.

  7. Rehospitalization

    Time frame: From 24 hours after the intervention to 6 months after randomization

    Incidence of rehospitalization

  8. Mortality

    Time frame: From 24 hours after the intervention to 6 months after randomization

    Incidence of mortality

  9. Incidence of Treatment-Related Adverse Events

    Time frame: 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.

  10. Plasma p-tau217 levels

    Time frame: Baseline

    Plasma levels of phosphorylated tau (p-tau217) will be measured in blood samples using standard clinical laboratory assays.

  11. Plasma Aβ42 levels

    Time frame: Baseline

    Plasma levels of Amyloid beta 42 (Aβ42) will be measured in blood samples using standard clinical laboratory assays.

  12. Change in plasma IL-6 levels

    Time frame: 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.

  13. Change in plasma s-RAGE levels

    Time frame: 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.

  14. Change in plasma GDF-15 levels

    Time frame: 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.

  15. Change in plasma GFAP levels

    Time frame: 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.

  16. Change in plasma NSE levels

    Time frame: 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.

  17. Change in plasma NfL levels

    Time frame: 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.

  18. Change in plasma FGF-1 levels

    Time frame: 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.

  19. Change in plasma BDNF levels

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Giuseppe Bellelli

CONTACT

[email protected]

+39 039 233 3472

Sponsors and collaborators

Lead sponsor

Fondazione IRCCS San Gerardo dei Tintori

Other

Registry information

Official study title

Palmitoylethanolamide/Luteolin for the Maintenance of Cognitive Performance in Older Adults Undergoing Cardiac Surgery

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
Jul 2, 2026
Registry last updated
Jul 2, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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