Efficacy of Ultra-micronized Palmitoylethanolamide (Um-PEA) in Geriatric Patients With Chronic Pain

N-of-1 Randomised Trials to Assess the Efficacy of Ultra-micronized Palmitoylethanolamide (Um-PEA) in Geriatric Patients With Chronic Pain

Investigators planned to adopt the N-of-1 trial approach to objectively test the effectiveness of ultra-micronized PEA at an individual level in our older outpatients. 65 years old or older persons referring to the Geriatric Unit of the Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico of Milan complaining of noncancer chronic pain of any origin will be eligible. Each trial will be a placebo-controlled randomized crossover trial including two um-PEA (600 mg twice a day) and placebo treatment pairs. Investigators will secondarily meta-analyse the performed N-of-1 trials to obtain an estimate of the average effect of um-PEA compared with placebo using a frequentist and Bayesian approach.

Study Overview

• Status: Completed
• Conditions: Chronic Pain
• Intervention / Treatment: Drug: ultra-micronized palmitoylethanolamide; Drug: Placebo

Detailed Description

Background: Chronic pain in the elderly is highly prevalent, often underestimated, and associated with adverse outcomes. Most available analgesic drugs are often either ineffective or not tolerated, and burdened with many side effects. Palmitoylethanolamide (PEA) is an endogenous widely distributed N-acylethanolamina involved in neuroinflammation and pain generating processes. Formulations containing ultra-micronized Palmitoylethanolamide (um-PEA) are available on the market but their effectiveness on chronic pain in highly heterogeneous geriatric patients is not clear and likely not generalizable. Investigators planned to adopt the N-of-1 trial approach to objectively test the effectiveness of ultra-micronized PEA at an individual level in our older outpatients.

Methods/Design: 65 years old or older persons referring to the Geriatric Unit of the Fondazione IRCSS Ca' Granda Ospedale Maggiore Policlinico of Milan complaining of noncancer chronic pain of any origin will be eligible. Each trial will be a placebo-controlled randomized crossover trial including two um-PEA (600 mg twice a day) and placebo treatment pairs. um-PEA or placebo 3-week periods will be separated by 2-week washout intervals to overcome the possible carryover effect. Pain intensity, need for on-demand analgesic medications, and impact on daily activities will be evaluated. Also, cognitively impaired patients will be eligible as long as the expression of pain can be recognized and its frequency assessed by a caregiver. Trial results will be then discussed with the patient/caregiver and the treating physician to decide whether to continue the treatment. The impact of the N-of-1 approach on the physician's management plan and confidence will be assessed. Investigators will secondarily meta-analyse the performed N-of-1 trials to obtain an estimate of the average effect of um-PEA compared with placebo using a frequentist and Bayesian approach.

Discussion: While pursuing an ultimate clinical objective, i.e. to empirically and objectively decide the best treatment choice for an individual older patient with chronic pain, these series of geriatric N-of-1 trials on PEA will bring the Evidence Based Medicine principles into the care of patients not usually represented in conventional randomized controlled trials, and realize a patient-centered outcome approach necessary to improve appropriate prescribing in elderly patients with multimorbidity and polypharmacy.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20122
    • Geriatric Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pain is located at the back (any level) and/or at the joints and/or at the limbs.
• The pain is chronic, i.e. it has been present for at least 6 months, even if with fluctuations.
• The pain is attributable to one or more of the following conditions: osteoarthritis/osteoarthrosis; spondylosis; radiculopathy; diabetic peripheral neuropathy; post-herpetic neuralgia; chronic idiopathic axonal polyneuropathy; fibromyalgia; or pain of uncertain origin or idiopathic, as long as it has had and it is expected to have a chronic nature, even if with spontaneous fluctuations.

Exclusion Criteria:

• cancer-related pain
• clear ischemic pathogenesis for pain (e.g. claudicatio intermittens or critical limb ischemia)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultra-micronized Palmitoylethanolamide; Ultra-micronized Palmitoylethanolamide 600 mg twice a day	Drug: ultra-micronized palmitoylethanolamide; ultra-micronized palmitoylethanolamide 600 mg twice a day; Other Names: Normast; um-PEA
Placebo Comparator: Placebo; Placebo tab twice a day	Drug: Placebo; um-PEA like placebo twice a day; Other Names: um-PEA like placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
daily intensity of pain assessed using a 11-point visual numeric scale, accompanied with labels and pictures, modified from Faces Pain Scale.	126 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
daily need of on-demand analgesic medications		126 days
impact of pain on daily activities (short questionnaire modified from the back pain functional scale)	The short questionnaire modified from the back pain functional scale consists of 12 items (but it can be modified to better fit to the patients). A score from 1 to 5 is assigned to each item.	126 days

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Investigators: Principal Investigator: Maura Marcucci, MD, MSc, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Publications and helpful links

General Publications

• Germini F, Coerezza A, Andreinetti L, Nobili A, Rossi PD, Mari D, Guyatt G, Marcucci M. N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients with Chronic Pain. Drugs Aging. 2017 Dec;34(12):941-952. doi: 10.1007/s40266-017-0506-2.
• Marcucci M, Germini F, Coerezza A, Andreinetti L, Bellintani L, Nobili A, Rossi PD, Mari D. Efficacy of ultra-micronized palmitoylethanolamide (um-PEA) in geriatric patients with chronic pain: study protocol for a series of N-of-1 randomized trials. Trials. 2016 Jul 29;17:369. doi: 10.1186/s13063-016-1496-9.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: February 21, 2016
• First Submitted That Met QC Criteria: March 3, 2016
• First Posted (Estimate): March 4, 2016

Study Record Updates

• Last Update Posted (Actual): September 11, 2019
• Last Update Submitted That Met QC Criteria: September 10, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• 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: Nof1-PEA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided