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

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Abstract

Background

Ultra-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.

Objective

The aim of this study was to determine the effectiveness of um-PEA versus placebo on chronic pain intensity and function in individual geriatric patients.

Design

We performed randomized, blinded N-of-1 trials with two 3-week um-PEA versus placebo comparisons, separated by 2-week washout periods.

Participants

The study included outpatients aged ≥ 65 years with chronic, non-cancer, non-ischemic pain in the back, joints, or limbs.

Intervention

Patients were randomized to Um-PEA 600 mg or placebo twice daily.

Measurements

Pain 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.

Results

Ten 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).

Conclusions

Our experience confirmed that N-of-1 trials may help make personalized evidence-based decisions in complex older patients, with special feasibility considerations.

ClinicalTrials.gov

NCT02699281.

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Acknowledgements

We thank the Epitech Group SpA for providing the study drugs and information on um-PEA pharmacology. We acknowledge the important contribution of the staff of the UOC Farmacia (hospital pharmacy) and of the UOC Geriatria (geriatric unit) of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico of Milan in conducting the study.

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Authors and Affiliations

  1. Geriatric Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy

    Federico Germini, Anna Coerezza, Paolo Dionigi Rossi, Daniela Mari & Maura Marcucci

  2. Department of Health Sciences, Università degli Studi di Milano, Milan, Italy

    Federico Germini

  3. Department of Health Research Methods, Evidence, and Impact (formerly Clinical Epidemiology and Biostatistics), McMaster University, 1280 Main St. W, Hamilton, ON, L8S 4K1, Canada

    Federico Germini, Gordon Guyatt & Maura Marcucci

  4. Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy

    Anna Coerezza, Luca Andreinetti, Daniela Mari & Maura Marcucci

  5. IRCCS-Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy

    Alessandro Nobili

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  1. Federico Germini
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  7. Gordon Guyatt
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Corresponding author

Correspondence to Maura Marcucci.

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The authors have no conflict of interest to disclose.

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None.

Informed consent

All participants provided informed consent at the beginning of the study.

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Germini, F., Coerezza, A., Andreinetti, L. et al. N-of-1 Randomized Trials of Ultra-Micronized Palmitoylethanolamide in Older Patients with Chronic Pain. Drugs Aging 34, 941–952 (2017). https://doi.org/10.1007/s40266-017-0506-2

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