Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PEALut® + Standard of Care | Experimental | Participants receive co-ultramicronized Palmitoylethanolamide + Luteolin (700 mg + 70 mg in 10 ml) in addition to Standard of Care |
|
| Standard of Care | Active Comparator | Participants receive only the Standard of Care |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Postoperative Cognitive Dysfunction (POCD) | 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Giuseppe Bellelli | Contact | +39 039 233 3472 | giuseppe.bellelli@unimib.it |
| Name | Affiliation | Role |
|---|---|---|
| Giuseppe Bellelli | School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fondazione IRCCS San Gerardo dei Tintori | Monza | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 6981735 | Background | 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. | |
| 9525362 | 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. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Standard of Care | Other | Standard of Care |
|
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) | 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) | 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) | 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 | 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 | Incidence of rehospitalization | From 24 hours after the intervention to 6 months after randomization |
| Mortality | Incidence of mortality | From 24 hours after the intervention to 6 months after randomization |
| Incidence of Treatment-Related Adverse Events | 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 | Plasma levels of phosphorylated tau (p-tau217) will be measured in blood samples using standard clinical laboratory assays. | Baseline |
| Plasma Aβ42 levels | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |
| 39058915 | 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. |
| 39399113 | 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. |
| 38615798 | 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. |
| 34069940 | 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. |
| 36387000 | 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. |
| 26706245 | 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. |
| ID | Term |
|---|---|
| D000079690 | Postoperative Cognitive Complications |
| D000090862 | Neuroinflammatory Diseases |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D009422 | Nervous System Diseases |
| D007249 | Inflammation |
Not provided
Not provided
| ID | Term |
|---|---|
| D047311 | Luteolin |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D047309 | Flavones |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
Not provided
Not provided