Micronized and Ultramicronized Palmitoylethanolamide in Fibromyalgia Patients

Efficacy and Tolerability of Micronized and Ultramicronized Palmitoylethanolamide in Fibromyalgia Patients: A Double-blind, Randomized, Placebo-controlled Clinical Trial

The onset of chronic Fibromyalgia symptomatology is due to central alterations, together with peripheral neuroimmune modifications. Using positron emission tomography (PET), it has been observed for the first time that fibromyalgia patients have a high activation of microglial cells compared to normal subjects. Experimental evidence in neuroinflammation models in vitro and in vivo have demonstrated the anti-inflammatory and neuroprotective effect of Palmitoylethanolamide (PEA), effects confirmed by observational clinical investigations conducted in patients with fibromyalgia in which micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA) reduced the intensity of pain improving the quality of life. The aim of this study is to investigate the efficacy and tolerability of PEA-m + PEA-um administered as an add-on therapy with a double-blind, randomized, placebo-controlled clinical investigation.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Dietary supplement: micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) microgranules; Drug: Standard Therapy; Drug: Rescue Drug; Other: Placebo microgranules 1800mg

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Epitech Group SpA Clinical Research; Phone Number: +39 049 8016784; Email: info@epitech.it

Study Locations

• Italy
  • VR
    • Verona, VR, Italy, 37126
      • Anestesia e Rianimazione B - Azienda Ospedaliera Universitaria Integrata di Verona

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of Fibromyalgia according to the criteria of the American College of Rheumatology 2016 (symptoms for at least 3 months, Widespread Pain Index (WPI) ≥ 7 and Symptom Severity (SS) ≥ 5 or WPI 4-6 and SS ≥ 9)
• Pain intensity assessed on the Visual Analogue Scale (VAS) ≥ 40
• PEA-naive patients
• Patients who agree to sign informed consent

Exclusion Criteria:

• Values of WPI <7 and SS <5
• Pain intensity assessed on the Visual Analogue Scale (VAS) <40
• Patients who have already taken PEA in the past
• Allergic or hypersensitive subjects to the product and / or one or more of its excipients
• Patients who refuse to sign informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1; Normast® MPS (mPEA and umPEA 300mg + 600mg) microgranules for sublingual use, 1800mg/die in 2 doses (morning and evening) for 90 days	Dietary supplement: micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) microgranules; Micronized and ultra-micronized Palmitoylethanolamide is on the market in Italy as a Food for Special Medical Purposes; Other Names: Normast® MPS microgranules; Drug: Standard Therapy; (antidepressants, anticonvulsants, muscle relaxants, weak opiates, etc..) consolidated for at least 3 months; Drug: Rescue Drug; Use as needed allowed; Other Names: Paracetamol or Fans
Placebo Comparator: Group 2; Placebo microgranules for sublingual use, 1800mg/die in 2 doses (morning and evening) for 90 days	Drug: Standard Therapy; (antidepressants, anticonvulsants, muscle relaxants, weak opiates, etc..) consolidated for at least 3 months; Drug: Rescue Drug; Use as needed allowed; Other Names: Paracetamol or Fans; Other: Placebo microgranules 1800mg; Placebo was prepared to be indistinguishable from color and flavor from the Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fibromyalgia symptoms assessed by Fibromyalgia Impact Questionnaire Revised	Change of Fibromyalgia symptoms	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Intensity assessed by Visual Analogue Scale	Change of Visual Analogue Scale every 30 days (0: no pain - 100 mm: maximum pain)	90 days
Health assessed by Short form-12 Health Survey	Change in Health at the end of treatment	90 days
Sleep Disorders assessed by Pittsburgh Sleep Quality Index	Change in sleep disorders at the end of treatment	90 days
Rescue Drugs consumption assessed by a daily diary	Change in rescue drugs consumption during the entire period	90 days
Incidence of Adverse Events	Monitoring of adverse event	90 days
Blood test	Clinically significant changes in blood test	90 days

Collaborators and Investigators

• Sponsor: Epitech Group SpA
• Collaborators: Azienda Ospedaliera Universitaria Integrata Verona
• Investigators: Principal Investigator: Enrico Polati, MD, Azienda Ospedaliera Universitaria Integrata di Verona

Publications and helpful links

General Publications

• Schweiger V, Martini A, Bellamoli P, Donadello K, Schievano C, Balzo GD, Sarzi-Puttini P, Parolini M, Polati E. Ultramicronized Palmitoylethanolamide (um-PEA) as Add-on Treatment in Fibromyalgia Syndrome (FMS): Retrospective Observational Study on 407 Patients. CNS Neurol Disord Drug Targets. 2019;18(4):326-333. doi: 10.2174/1871527318666190227205359.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2020
• Primary Completion (Actual): May 2, 2022
• Study Completion (Actual): May 2, 2022

Study Registration Dates

• First Submitted: July 20, 2020
• First Submitted That Met QC Criteria: July 24, 2020
• First Posted (Actual): July 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; 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: MPS-FM

Drug and device information, study documents

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