Pain alleviation in diabetic neuropathy using hybrid closed loop insulin pumps (PAINLESS) – A randomised crossover trial protocol
- 1School of Medicine and Population Health, University of Sheffield, Sheffield, United Kingdom
- 2Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
- 3Diabetes Research Centre, University of Leicester, Leicester, United Kingdom
Abstract
Introduction: 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. Materials and methods: 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. Timelines: 24-month trial: 18 months recruitment/follow up, 6 months close-out, analyses and dissemination. Registration Details: ISRCTN24233750.
Related
- Treatment of diabetic foot chronic ulcers and neuropathy with placenta-derived stem cells
- Editorial: Frontiers in diagnostic and therapeutic approaches in diabetic sensorimotor neuropathy, volume II
- Comparative Effectiveness of Tricyclic Antidepressants, Serotonin–Norepinephrine Reuptake Inhibitors, and Anticonvulsants for Diabetic Painful Neuropathy: A Systematic Review and Meta-Analysis
- Long-Term Effects of Paced Heart Rate on Central Blood Pressure in Patients with Sinus Node Dysfunction and Hypertension: A Randomised Crossover Study
- Mitochondrial Dysfunction in Diabetic Neuropathy: An Evidence Map of Molecular Mechanisms, Translational Biomarkers, and Emerging Implications for Oral Neuropathy-A Scoping Review.
BibTeX
@article{berry2026pain,
title = {{Pain alleviation in diabetic neuropathy using hybrid closed loop insulin pumps (PAINLESS) – A randomised crossover trial protocol}},
author = {Simon Alexander Berry and Ahmed Iqbal and Jackie Elliott and Rajiv Gandhi and Abdul Paracha and Vaios Koutroukas and Mohummad Shaan Goonoo and Mahnoor Fatima Haq and Andrew Gerges and Gordon Sloan and Solomon Tesfaye and Pratik Choudhary and Dinesh Selvarajah},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357573},
url = {https://doi.org/10.1371/journal.pone.0357573},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pain alleviation in diabetic neuropathy using hybrid closed loop insulin pumps (PAINLESS) – A randomised crossover trial protocol
AU - Simon Alexander Berry
AU - Ahmed Iqbal
AU - Jackie Elliott
AU - Rajiv Gandhi
AU - Abdul Paracha
AU - Vaios Koutroukas
AU - Mohummad Shaan Goonoo
AU - Mahnoor Fatima Haq
AU - Andrew Gerges
AU - Gordon Sloan
AU - Solomon Tesfaye
AU - Pratik Choudhary
AU - Dinesh Selvarajah
PY - 2026
DA - 2026/09/08
JO - PLOS One
DO - 10.1371/journal.pone.0357573
UR - https://doi.org/10.1371/journal.pone.0357573
AB - Introduction: 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. Materials and methods: 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. Timelines: 24-month trial: 18 months recruitment/follow up, 6 months close-out, analyses and dissemination. Registration Details: ISRCTN24233750.
SN - 1932-6203
ER -