A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain

Abstract

Abstract Background Peripheral neuropathy is a common complication of diabetes. The management of the associated neuropathic pain remains difficult to treat. Objective This study explored the safety, tolerability and efficacy of a palmitoylethanolamide (PEA) formulation in treating diabetic-related peripheral neuropathic pain (PNP). Secondary outcomes included systemic inflammation, sleep and mood changes in patients diagnosed with type 1 and type 2 diabetes and PNP. Design This study was a single-centre, quadruple-blinded, placebo-controlled trial with 70 participants receiving 600 mg of PEA or placebo daily, for 8 weeks, with a 94% rate of study participation completion. Primary outcomes were neuropathic pain and specific pain types (the BPI-DPN and NPSI). The secondary outcomes were sleep quality (MOS sleep scale), mood (DASS-21), glucose metabolism and inflammation. Results There was a significant reduction (P ≤ 0.001) in BPI-DPN total pain and pain interference, NPSI total score and sub-scores, except for evoked pain (P = 0.09) in the PEA group compared with the placebo group. The MOS sleep problem index and sub-scores significantly improved (P ≤ 0.001). DASS-21 depression scores significantly reduced (P = 0.03), but not anxiety or stress scores. Interleukin-6 and elevated C-reactive protein levels significantly reduced in the PEA group (P = 0.05), with no differences in fibrinogen between groups (P = 0.78) at treatment completion. There were no changes in safety pathology parameters, and the treatment was well tolerated. Conclusions The study demonstrated that the PEA formulation reduced diabetic peripheral neuropathic pain and inflammation along with improving mood and sleep. Further studies on the mechanistic effectiveness of PEA as an adjunct medicine and as a monotherapy pain analgesic are warranted. Clinical Trial Registration Registry name: Australian New Zealand Clinical Trials Registry (ANZCTR), Registration number: ACTRN12620001302943, Registration link: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380826, Actual study start date: 20 November 2020.