Micronized and Ultramicronized Palmitoylethanolamide in COVID-19 Patients

Efficacy of Palmitoylethanolamide, in add-on to Standard Therapy, on Inflammatory Markers of Patients With Interstitial Pneumonia Due to COVID-19. A Pilot Controlled, Randomized, Open Lable Clinical Study

SARS-CoV-2 infection is a condition characterized by excessive leukocyte infiltration, massive release of chemokines, proteases and cytokines, the so-called "cytokine storm", which promote the inflammatory process and contribute to exacerbation of COVID-19 symptomatology. Because of the abnormal release of pro-inflammatory cytokines by non-neuronal cells of the immune system, such as the mast cells in periphery, and microglia at central level, the body activates a defensive neuroinflammatory process that, if not controlled, can become pathological. Therefore it's important to intervene early on neuroinflammation, in order to limit the progression of the disease.

A possible intervention is represented by Palmitoylethanolamide (PEA), an endogenous molecule of the N-acylethanolamine family synthesized "on demand" in response to "stress factors" to restore tissue homeostasis, able to control mast cells and microglia uncontrolled activation. Experimental evidence in vitro and in vivo demonstrated the anti-inflammatory and neuroprotective effect of micronized and ultra-micronized PEA (mPEA and umPEA), confirmed in various clinical investigations conducted in patients with different pathological conditions. The aim of this study is to investigate the efficacy of a compound containing mPEA + umPEA on peripheral inflammatory markers, neuroinflammation, and others clinical parameters in intensive care patients with COVID-19 interstitial pneumonia.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Dietary supplement: Micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) oral suspension; Combination product: Standard Therapy

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Roma, Italy, 00189
    • Anestesia e Rianimazione Azienda Ospedaliera Universitaria Sant'Andrea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Intensive Care Unit Hospitalization for interstitial pneumonia due to COVID-19 diagnosis (nasal swab/sputum/bronchoalveolar lavage positive for Sars-Cov-2 infection)

Exclusion Criteria:

• Pregnancy or breastfeeding;
• Known allergy or hypersensitivity to the product or its excipients;
• Inability to take the product per os or via nasogastric tube.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PEA Group; Normast® MPS (mPEA and umPEA 300mg + 600mg) oral suspension: 2700mg/die in 3 doses for 28 days, in add-on to standard therapy	Dietary supplement: Micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) oral suspension; Micronized and ultra-micronized Palmitoylethanolamide is on the market in Italy as a Food for Special Medical Purposes; Other Names: Normast® MPS oral suspension; Combination product: Standard Therapy; Standard therapy established for individual patients
Other: Control Group; Standard therapy only	Combination product: Standard Therapy; Standard therapy established for individual patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of responder participants after 7 days of treatment	Responder: decrease ≥ 30% from baseline of IL-6 blood levels	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of pro-inflammatory markers (IL-6, IL-1 alpha, IL-1 beta, TNF-alpha, PCR, PCT, neopterin)		0, 3, 7, 14, 28 days
Change of anti-inflammatory markers (IL-4, IL-10)		0, 3, 7, 14, 28 days
Change of brain damage markers (S100b, ENS)		0, 3, 7, 14, 28 days
Change of coagulation indices (INR, fibrinogen, D-dimer)		0, 3, 7, 14, 28 days
Change of hematological parameters	leukocyte formula (lymphocytes, CD4 / CD8 ratio)	0, 3, 7, 14, 28 days
Change of oxygenation indices (P/F ratio, lactates)		0, 3, 7, 14, 28 days
Number of participants who developed delirium	Confusion Assessment Method-Intensive Care Unit (CAM-ICU) (0-1: no delirium; >1 delirium)	0, 3, 7, 14, 28 days
Number of participants who developed anxiety and/or depression	Hospital Anxiety and Depression Scale (HADS) (0: normal; 21: severe)	0, 3, 7, 14, 28 days

Other Outcome Measures

Outcome Measure	Time Frame
Number of days of invasive mechanical ventilation (orotracheal intubation - IOT)	28 days
Number of days of non-invasive mechanical ventilation (Helmet, face mask)	28 days
Number of days of intensive care (ICU) hospitalization	28 days

Collaborators and Investigators

• Sponsor: Epitech Group SpA
• Collaborators: Azienda Ospedaliera "Sant'Andrea"
• Investigators: Principal Investigator: Prof.ssa Flaminia Coluzzi, MD, Azienda Ospedaliera Universitaria Sant'Andrea di Roma

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2020
• Primary Completion (Actual): February 28, 2021
• Study Completion (Actual): February 28, 2021

Study Registration Dates

• First Submitted: September 24, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): September 29, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2021
• Last Update Submitted That Met QC Criteria: August 24, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Palmidrol
• Other Study ID Numbers: NORM_MPS-COVID; NORM_MPS_11 (Other Identifier: Epitech Group)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No