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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chronic Pain

Intervention / Treatment
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* Drug: ultra-micronized palmitoylethanolamide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |