N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients with Chronic Pain

BackgroundUltra-micronized palmitoylethanolamide (um-PEA) represents an attractive option for chronic pain control in complex older patients at higher risk of adverse effects with traditional analgesics.ObjectiveThe aim of this study was to determine the effectiveness of um-PEA versus placebo on chronic pain intensity and function in individual geriatric patients.DesignWe performed randomized, blinded N-of-1 trials with two 3-week um-PEA versus placebo comparisons, separated by 2-week washout periods.ParticipantsThe study included outpatients aged ≥ 65 years with chronic, non-cancer, non-ischemic pain in the back, joints, or limbs.InterventionPatients were randomized to Um-PEA 600 mg or placebo twice daily.MeasurementsPain intensity was measured using an 11-point visual numeric scale. Functional impairment was measured using a Back Pain Functional Scale. Impact of each N-of-1 trial was measured on the clinician’s intention to treat and confidence.ResultsTen of 11 eligible patients consented over 7 months [all female, mean age 83.2 years (SD 4.6)]. Three patients interrupted the trial: one had diarrhea (under placebo), one for low adherence, and one for intercurrent pneumonia. A small statistically significant effect in favor of um-PEA was seen at the mixed method analyses in two patients (effect size equal to 8% of the baseline pain). A statistically significant impact on function was found in one patient. After the trial, um-PEA was prescribed to four patients; in two patients the clinician changed their pre-trial intention to treat; the clinician confidence in the treatment plan either increased (5) or remained the same (2).ConclusionsOur experience confirmed that N-of-1 trials may help make personalized evidence-based decisions in complex older patients, with special feasibility considerations.ClinicalTrials.govNCT02699281.