Palmitoylethanolamide for Chronic Inflammatory Pain Conditions

Randomized Placebo-Controlled Trial of Palmitoylethanolamide for Chronic Inflammatory Pain Conditions

The goal of this clinical trial is to evaluate if a supplement called palmitoylethanolamide (PEA) is effective in reducing the pain in patients with chronic inflammatory pain conditions. The main question the trial aims to answer is if PEA works better at treating a patients pain and improving their function better than a placebo.

Participants will be divided into two equal groups and asked to take either PEA or a placebo for 8 weeks.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain
• Intervention / Treatment: Drug: Palmitoylethanolamide 600mg twice a day; Other: placebo

Detailed Description

Chronic inflammatory pain conditions, such as rheumatoid arthritis, fibromyalgia, and neuropathic pain syndromes, present a significant burden on individuals and healthcare systems worldwide. Despite advancements in pain management, many patients continue to experience inadequate relief, and the long-term use of conventional analgesics can be associated with adverse effects.

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide that has garnered attention in recent years for its potential therapeutic properties in managing chronic inflammatory pain. PEA is an endogenous lipid mediator and a member of the N-acylethanolamine family. It exerts its effects primarily by interacting with peroxisome proliferator-activated receptor alpha (PPAR-α) and through other molecular pathways involved in neuroinflammation and immune responses.

In Europe where nutraceuticals are more commonly used in conventional practice, research on PEA has shown significant promise in studies on inflammatory pain conditions such as chronic pelvic pain, irritable bowel syndrome, temporomandibular joint arthritis and knee osteoarthritis. Similar studies have not been completed in the United States.

1. Anti-Inflammatory Effects:

   - PEA has demonstrated anti-inflammatory properties by modulating immune responses, inhibiting mast cell activation, and reducing the release of pro-inflammatory cytokines. These effects suggest its potential in attenuating the underlying inflammation in chronic pain conditions.

2. Analgesic Effects:

   - Several animal studies have reported that PEA can alleviate pain in models of neuropathic pain, inflammatory pain, and even in more complex pain conditions like fibromyalgia. These findings suggest that PEA may have a role as an analgesic agent.

3. Safety and Tolerability:

   - PEA is generally well-tolerated with a favorable safety profile. Clinical trials and real-world studies have reported minimal side effects, making it a potentially attractive option for long-term use in chronic pain management.

4. Clinical Trials:

   - Some clinical trials have explored the use of PEA in specific chronic pain conditions. While results have been promising, larger, well-controlled trials are needed to establish its efficacy conclusively.

5. Mechanisms of Action:

   • Beyond PPAR-α activation, PEA may also influence other cellular pathways involved in pain modulation, such as TRPV1 channels and GPR55 receptors, although the exact mechanisms are still being elucidated.

Summary of previous trials:

A recent systematic review and meta-analysis of no US studies suggests that PEA is an effective and well-tolerated treatment for chronic pain. The literature search identified 253 unique articles with 11 included in the meta-analysis. The 11 articles had a combined sample size of 774 patients with diverse chronic pain conditions who took a dose of 400-1200 mg of a PEA supplement or a placebo over periods ranging from 2 to 12 weeks. The studies showed significantly better pain reduction compared to placebo with no adverse effects.

Given the growing interest in PEA as a potential therapeutic agent for chronic inflammatory pain, and the lack of any known side effects of this supplement, this randomized placebo-controlled trial aims to contribute valuable data to the existing body of research. By rigorously evaluating the efficacy and safety of PEA in a controlled clinical setting, the investigators seek to provide evidence-based insights into its role in managing chronic inflammatory pain conditions and further inform clinical practice.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Brian McLean Pain Physician, MD; Phone Number: 619-532-8495; Email: brian.c.mclean.mil@health.mil
• Study Contact Backup: Name: IRB Administrator; Phone Number: 619-532-9083; Email: kristina.m.umali.civ@health.mil

Study Locations

• United States
  • California
    • San Diego, California, United States, 92118
      • Recruiting
      • Naval Medical Center San Diego
      • Contact: Naval Medical Center Institutional Review Board; Phone Number: 619-532-9927; Email: kristina.m.umali.civ@health.mil
      • Principal Investigator: Brian McLean COL, USA MC, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Chronic Inflammatory Pain of greater than 3 months duration and greater than or equal to 5/10 intensity that has not responded to other conservative therapies such as rest, ice, compression or other oral medications.

Exclusion Criteria:

• Severe allergy to any specific food component such as nut, egg or soy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Palmitoylethanolamide; Participants randomized to the experimental arm will receive the supplement Palmitoylethanolamide (PEA) at a dose of 600mg twice a day	Drug: Palmitoylethanolamide 600mg twice a day; 600mg palmitoylethanolamide twice a day; Other Names: PEA
Placebo Comparator: Placebo; Participants randomized to the placebo arm will receive a visually identical placebo capsule	Other: placebo; visually identical placebo capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain Level	Pain level will be assessed using the Defense and Veterans Pain Rating Scale (DVPRS) Where the minimum value is 0 indicating no pain and the maximum value is 10 indicating worst possible pain	4 and 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain interference and function	Daily Pain Impact (interference with activity, sleep, mood, stress) (0-10 scale with 0 being the best and 10 being the worst outcome)	4 and 8 weeks
Pain Catastrophizing Scale (PCS)	Pain Catastrophizing Scale (PCS) (Helplessness; Magnification; Rumination) (0-52 scale with 0 being the best and 52 being the worst outcome)	4 and 8 weeks
Patient Reported Outcome Measurement Information System (PROMIS) (Pain interference, Social satisfaction; Physical function)	PROMIS (Pain interference, Social satisfaction; Physical function) (0-10 each with 0 being the worst and 10 being the best outcome)	4 and 8 Weeks

Collaborators and Investigators

• Sponsor: Navy Medical Center San Diego

Study record dates

Study Major Dates

• Study Start (Estimated): August 5, 2024
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): October 30, 2025

Study Registration Dates

• First Submitted: February 6, 2024
• First Submitted That Met QC Criteria: February 15, 2024
• First Posted (Actual): February 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 15, 2024
• Last Update Submitted That Met QC Criteria: August 13, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: chronic pain; supplement; alternative therapy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Chronic Pain; 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: NMCSD.2024.0006

Drug and device information, study documents

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