Effects of PEA-LUT on Frontal Lobe Functions and GABAergic Transmission in Long-Covid Patients (PL-PC19)

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.

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

Study Overview

• Status: Completed
• Conditions: COVID-19; Fatigue; Cognitive Deficit; Neurophysiologic Abnormality
• Intervention / Treatment: Dietary supplement: palmitoylethanolamide co-ultramicronized with antioxidant flavonoid luteolin (PEA-LUT); Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • BZ
    • Vipiteno, BZ, Italy, 39049
      • Hospital of Vipiteno-Sterzing

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEA-LUT; 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); assumption of the product at dosage of 700/70 mg 2 time/day for 8 weeks
Placebo Comparator: Placebo; patients were required to assume granulated placebo, 2 time/day for 8 weeks	Dietary supplement: Placebo; assumption of a placebo product 2 time/day for 8 weeks

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes in Montreal Cognitive Assessment score	changes in Montreal Cognitive Assessment score, for evaluating the global cognition, are expected	Montreal Cognitive Assessment was assessed at enrollment and after 8 weeks of treatment duration
changes in Frontal Assessment Battery score	changes in Frontal Assessment Battery score, for evaluating the executive functions, are expected	Frontal Assessment Battery was assessed at enrollment and after 8 weeks of treatment duration

Collaborators and Investigators

• Sponsor: Department of Neurorehabilitation, Hospital of Vipiteno-Sterzing (BZ) Italy
• Collaborators: I.R.C.C.S. Fondazione Santa Lucia
• Investigators: Study Director: Leopold Saltuari, Md, Department of Neurorehabiliation - Hospital of Vipiteno-Sterzing

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2021
• Primary Completion (Actual): February 15, 2022
• Study Completion (Actual): March 15, 2022

Study Registration Dates

• First Submitted: March 30, 2022
• First Submitted That Met QC Criteria: April 1, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2022
• Last Update Submitted That Met QC Criteria: September 22, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: fatigue; cognitive deficits; post-covid19 syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurocognitive Disorders; COVID-19; Fatigue; Cognitive Dysfunction; Cognition Disorders; 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; Protective Agents; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Antioxidants; Palmidrol
• Other Study ID Numbers: PEA-LUT-in-Post-Covid-19

Drug and device information, study documents

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