Micronized and Ultramicronized Palmitoylethanolamide in Fibromyalgia Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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Fibromyalgia

Intervention / Treatment
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* Dietary Supplement: micronized and ultra-micronized Palmitoylethanolamide (mPEA and umPEA, 300mg + 600mg) microgranules
* Other: Placebo microgranules 1800mg
* Drug: Standard Therapy
* Drug: Rescue Drug


Participation Criteria
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Eligibility Criteria
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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

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |