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

• ClinicalTrials.gov Identifier: NCT02699281
• Recruitment Status: Completed
• First Posted: March 4, 2016
• Last Update Posted: September 11, 2019
• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Information provided by (Responsible Party): Maura Marcucci, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Tracking Information

• First Submitted Date: February 21, 2016
• First Posted Date: March 4, 2016
• Last Update Posted Date: September 11, 2019
• Study Start Date: October 2015
• Actual Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 3, 2016): daily intensity of pain assessed using a 11-point visual numeric scale, accompanied with labels and pictures, modified from Faces Pain Scale. [ Time Frame: 126 days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 3, 2016)

• daily need of on-demand analgesic medications [ Time Frame: 126 days ]
• impact of pain on daily activities (short questionnaire modified from the back pain functional scale) [ Time Frame: 126 days ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Pain

Intervention

• Drug: ultra-micronized palmitoylethanolamide
  ultra-micronized palmitoylethanolamide 600 mg twice a day
  Other Names:

  • um-PEA
  • Normast
• Drug: Placebo
  um-PEA like placebo twice a day
  Other Name: um-PEA like placebo

Study Arms

• Experimental: Ultra-micronized Palmitoylethanolamide
  Ultra-micronized Palmitoylethanolamide 600 mg twice a day
  Intervention: Drug: ultra-micronized palmitoylethanolamide
• Placebo Comparator: Placebo
  Placebo tab twice a day
  Intervention: Drug: Placebo

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 10, 2019): 11
• Original Estimated Enrollment (submitted: March 3, 2016): 12
• Actual Study Completion Date: July 2016
• Actual Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT02699281
• Other Study ID Numbers: Nof1-PEA
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Maura Marcucci, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Original Responsible Party: Same as current
• Current Study Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
• Verification Date: September 2019