Palmitoylethanolamide and Luteolin in Patients with Acute Ischemic Stroke

Efficacy of Palmitoylethanolamide and Luteolin on Early Functional Recovery in Acute Stroke Patients Treated with Thrombectomy: a Pilot Randomized Placebo-controlled Prospective Study

Acute ischemic stroke is caused by reduced blood supply to the brain associated with neuroinflammation. This mechanism contributes to acute neuronal death and persists even after reopening of the closed vessel, with consequent limitation of clinical and functional improvement.

Experimental and clinical evidence demonstrated the anti-inflammatory and neuroprotective effect of micronized and ultramicronized Palmitoylethanolamide (PEA).

The aim of this study is to evaluate the effect of co-ultramicronized PEA and luteolin (700 mg + 70 mg in 10 ml) on the clinical outcomes of patients with acute ischemic stroke undergoing mechanical thrombectomy.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke AIS
• Intervention / Treatment: Dietary supplement: co-ultramicronized Palmitoylethanolamide + Luteolin (770 mg); Procedure: Thrombectomy; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marcello Naccarato, MD, PhD; Phone Number: +39 0403994569; Email: marcello.naccarato@asugi.sanita.fvg.it
• Study Contact Backup: Name: Paola Caruso, MD; Phone Number: +39 0403994569; Email: paola.caruso@asugi.sanita.fvg.it

Study Locations

• Italy
  • Trieste, Italy
    • Azienda Sanitaria Universitaria Giuliano Isontina
    • Contact: Marcello Naccarato, MD, PhD; Phone Number: +39 0403994569; Email: marcello.naccarato@asugi.sanita.fvg.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age ≥ 60 years
• both genders
• first acute ischemic stroke in the middle cerebral artery area confirmed by angio-CT and CTP, eligible for mechanical thrombectomy according to national guidelines
• NIHSS > 6
• compliant patients
• signed informed consent

Exclusion Criteria:

• hemorrhagic stroke
• previous stroke (TIA, ischemic or hemorrhagic stroke)
• presence of clinically evident neurodegenerative diseases (Alzheimer's disease, Parkinson's disease)
• presence of psychiatric comorbidity (schizophrenia, bipolar disorder, depressive syndrome)
• presence of chronic inflammatory diseases (chronic inflammatory bowel disease, vasculitis etc.)
• current or previous neoplasia
• uncontrolled diabetes mellitus (glycemia on admission >400 mg/dL or <50 mg/dL)
• dysphagia, with inability to feed orally
• inability to provide informed consent
• pre-existing disability (pre-stroke mRS >2)
• allergy or hypersensitivity to the study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment group; co-ultramicronized Palmitoylethanolamide + Luteolin oral suspension (700 mg + 70 mg in 10 ml) in add-on to mechanical thrombectomy	Dietary supplement: co-ultramicronized Palmitoylethanolamide + Luteolin (770 mg); oral suspension, 10 ml twice a day (every 12 hours) for 7 days; Other Names: Glialia® oral suspension; PEALUT® oral suspension; Procedure: Thrombectomy; Endovascular Thrombectomy in all eligible patients, according to national acute stroke treatment guidelines
Placebo Comparator: Control group; Placebo oral suspension in add-on to mechanical thrombectomy	Procedure: Thrombectomy; Endovascular Thrombectomy in all eligible patients, according to national acute stroke treatment guidelines; Other: Placebo; oral suspension,10 ml twice a day (every 12 hours) for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the mean neurological disability score assessed by National Institutes of Health Stroke Scale (NIHSS), at 3 and 7 days (end of treatment) after hospitalization, between the two groups	NIHSS score ranges from 0 to 42, with higher scores indicating more severe neurological deficit	Baseline-hospitalization, 3 and 7 days
Change from baseline in the mean functional disability score assessed by modified Rankin Scale (mRS), at 7 days after hospitalization, between the two groups	mRS consists of 6 grades from 0 to 5, with 0 corresponding to no symptoms and 5 corresponding to severe disability	Baseline-hospitalization and 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of death and/or major vascular events (recurrent strokes, myocardial ischemia or peripheral arterial ischemia) from baseline to 7 days after hospitalization, between the two groups		From baseline to 7 days
Change from baseline of inflammatory and brain damage mediators [interleukin- 6 (IL-6), matrix metalloproteinase- 9 (MMP-9) and neurofilament light (NfL)] plasma levels at 3 and 7 days after hospitalization, between the two groups		Baseline-hospitalization, 3 and 7 days
Volume of restored penumbra	Volume of initial penumbra on admission CT perfusion scans not evolved to ischemic lesion on follow-up CT scan at 72 hrs since stroke onset	Baseline-hospitalization, 3 days

Collaborators and Investigators

• Sponsor: Ospedali Riuniti Trieste
• Investigators: Principal Investigator: Marcello Naccarato, MD, PhD, Azienda Sanitaria Universitaria Giuliano Isontina (ASU GI)

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 10, 2025
• First Submitted That Met QC Criteria: January 10, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 10, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Stroke; Neuroinflammation; Palmitoylethanolamide; Luteolin
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Ischemic Stroke; Stroke; Ischemia; Anti-Infective Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antirheumatic Agents; Sensory System Agents; Antiviral Agents; Analgesics, Non-Narcotic; Analgesics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Palmidrol
• Other Study ID Numbers: PEALUT - STROKE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No