Pain alleviation in diabetic neuropathy using hybrid closed loop insulin pumps (PAINLESS) - A randomised crossover trial protocol.

Abstract

Painful diabetic neuropathy (PDN) is a common complication of diabetes that leads to significant co-morbidity. Emerging evidence suggests glycaemic variability may be linked to fluctuations in pain intensity. Hybrid closed loop (HCL) systems reduce glycaemic variability, raising the possibility that they may modify pain intensity. This study aims to evaluate the effects of HCL use on pain intensity in people with PDN. PAINLESS is a two-centre, randomised cross-over study, recruiting 49 adults with type 1 diabetes and PDN. Each participant will complete two 12-week intervention periods in a randomised sequence (1:1): one with standard care including continuous glucose monitoring (CGM) and one with HCL using the Tandem t:slim X2 insulin pump with Control-IQ technology. The primary outcome is the change in 7-day average 24-hour pain intensity [rated on a numerical scale from 0-10 (NRS)] from baseline to the end of each 12-week intervention period as measured by daily pain diaries. Secondary outcomes include measures of pain trajectory/durability [responder rates (30% and 50% pain reduction in 7-day NRS), and the AUC for daily NRS scores], functional and quality of life outcomes [Short Form Health Survey (SF-36), and Short Form of the Brief Pain Inventory (BPI-MSF)], mood [Beck Depression Inventory (BDI)], health status [EQ-5D-5L], and global improvement [participant and clinician reported global impression of change]. Exploratory endpoints will harness neurophysiological assessments including Sudoscan, DPN-Check, Vagus and Vibrosense, and sleep and activity data from Withings devices. Statistical analyses will employ an intention-to-treat approach and mixed effect models. 24-month trial: 18 months recruitment/follow up, 6 months close-out, analyses and dissemination. ISRCTN24233750.