Effects of PEA-LUT on Frontal Lobe Functions and GABAergic Transmission in Long-Covid Patients

Study Overview
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Brief Summary
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The study explore the efficacy of PEA-LUT in patients suffering from neurological symptoms of Long-Covid

Detailed Description
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Aim of this study was testing the possible therapeutic effects of an 8-week therapy with PEA-LUT on GABAB-ergic neurotransmission, LTP-like synaptic plasticity, indexed with transient potentiation of motor evoked potentials (MEP) amplitude after repetitive TMS given as intermittent theta burst stimulation (iTBS) in long COVID patients with cognitive complaints and fatigue.

Official Title
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Effects of Palmitoylethanolamide Co-ultramicronized With Luteoline (Pea-lut) on Frontal Lobe Functions and GABAergic Transmission in Long Covid Patients. An 8-week Randomized Controlled Trial.

Conditions
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Fatigue, Cognitive Deficit, COVID-19, Neurophysiologic Abnormality

Intervention / Treatment
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* Dietary Supplement: palmitoylethanolamide co-ultramicronized with antioxidant flavonoid luteolin (PEA-LUT)
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: previous diagnosis of SARS-CoV-2 infection confirmed through detection of virus RNA by polymerase chain reaction (PCR) testing of a nasopharyngeal swab; subsequent recovery from infection as defined by two consecutive negative PCR tests separated by at least a day; mild form of COVID-19 (symptoms may include fever, cough, sore throat, malaise, myalgia, anorexia, nausea, diarrhoea, anosmia and ageusia) without necessitating hospital admission; complaints of cognitive difficulties and/or sense of fatigue, persisting after SARS-CoV-2 infection. Exclusion Criteria: prior or concurrent diagnosis of neurological, psychiatric, endocrine, metabolic or cardiopulmonary conditions; clinical and/or radiological evidence of COVID-19 related pneumonia during the active phase of the disease; anaemia; current pharmacological treatment with corticosteroids, antihistamines, antihypertensives, diuretics, antidepressants, anxiolytic or hypnotic drugs at the time of study

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants are randomized and assigned to one of two or more groups in parallel for the duration of the study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEA-LUT<br>patients were required to assume granulated PEA-LUT 700/70 mg, 2 time/day for 8 weeks | Dietary Supplement: palmitoylethanolamide co-ultramicronized with antioxidant flavonoid luteolin (PEA-LUT)<br>* assumption of the product at dosage of 700/70 mg 2 time/day for 8 weeks<br>|
| Placebo Comparator: Placebo<br>patients were required to assume granulated placebo, 2 time/day for 8 weeks | Dietary Supplement: Placebo<br>* assumption of a placebo product 2 time/day for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in % of test amplitude in LICI 100 | changes % of test amplitude in long-interval intracortical inhibition, indexing intracortical GABAB-ergic, transmission, are expected | LICI 100 was assessed two times, at enrollment and after 8 weeks of treatment duration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in % of test amplitude in SAI 20 | changes % of test amplitude in short-latency afferent inhibition, to evaluate M1 inhibition induced by sensory afferents, are expected | SAI 20 was assessed two times, at enrollment and after 8 weeks of treatment duration | 
| change in LTP-like cortical plasticity | change of MEP modulation after intermittent theta burst stimulation (iTBS) | LTP-like cortical plasticity was assessed at two times, at enrollment and after 8 weeks of treatment duration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fatigue, cognitive deficits, post-covid19 syndrome