Micronized and Ultramicronized Palmitoylethanolamide in COVID-19 Patients

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Covid19

Intervention / Treatment
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* Dietary Supplement: Micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) oral suspension
* Combination Product: Standard Therapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PEA Group<br>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<br>* Micronized and ultra-micronized Palmitoylethanolamide is on the market in Italy as a Food for Special Medical Purposes<br>* Other names: Normast® MPS oral suspension;Combination Product: Standard Therapy<br>* Standard therapy established for individual patients<br>|
| Other: Control Group<br>Standard therapy only | Combination Product: Standard Therapy<br>* Standard therapy established for individual patients<br>|

What is the study measuring?
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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 |