Painful diabetic neuropathy (PDN) is a frequent and disabling complication of diabetes, associated with reduced quality of life and significant morbidity. The trial rationale is that fluctuations in glucose — glycaemic variability — have been associated with changes in pain intensity in people with diabetes. Hybrid closed loop (HCL) insulin delivery systems reduce glycaemic variability compared with standard insulin management, raising the hypothesis that HCL use may modify pain intensity in PDN.
The PAINLESS protocol was developed to evaluate whether sustained use of an HCL system affects patient‑reported pain intensity and related functional, mood, and health status outcomes in adults with type 1 diabetes and PDN.
PAINLESS is a two‑centre, randomised, crossover study. The crossover design means each participant serves as their own control, completing two consecutive 12‑week intervention periods in randomized order. The target sample size in the protocol is 49 adults with type 1 diabetes and PDN. The trial will be conducted across two participating centres in the United Kingdom as described in the source affiliations.
Participants are adults with type 1 diabetes who have painful diabetic neuropathy. The trial abstract does not report the full inclusion and exclusion criteria or detailed baseline characteristics in the abstract; those details are not provided in the source summary and therefore are not reported here. Screening, enrollment, and consent procedures were not described in the abstract.
Each participant completes two 12‑week periods in randomized sequence (1:1):
Standard care including continuous glucose monitoring (CGM). The abstract indicates CGM is part of the standard care comparator but does not specify device brands for the CGM-only arm.
Hybrid closed loop (HCL) therapy using the Tandem t:slim X2 insulin pump with Control‑IQ technology. Participants assigned to this arm will use the HCL system for the 12‑week intervention period. Specific training, run‑in, or device optimization procedures were not detailed in the abstract.
No washout duration between periods is mentioned in the abstract; the crossover timing beyond the two 12‑week periods is not further specified in the summary.
Primary outcome
The primary outcome is the change in 7‑day average 24‑hour pain intensity measured on a numerical rating scale (NRS) from 0 to 10. Pain intensity is recorded in daily pain diaries and compared from baseline to the end of each 12‑week intervention period.
Secondary outcomes
Secondary endpoints encompass measures of pain trajectory and durability, function, quality of life, mood, health status, and global improvement. Specifically reported secondary measures include:
The abstract does not report specific thresholds, handling of missing data, or multiplicity corrections for secondary outcomes.
Exploratory endpoints will include targeted neurophysiological testing and objective activity/sleep monitoring. The neurophysiological measures listed in the protocol abstract are Sudoscan, DPN‑Check, Vagus, and Vibrosense. In addition, sleep and activity data will be captured using Withings devices. The abstract does not provide detailed test schedules, scoring protocols, or how these exploratory outcomes will be integrated into primary/secondary analyses.
Analyses will be performed on an intention‑to‑treat basis. The abstract indicates use of mixed effect models for primary statistical comparisons, which are appropriate for crossover and repeated measures data. Responder rate analyses and AUC calculations are specified as secondary/trajectory analyses. The abstract does not include detailed statistical plans, sample size calculations, power estimates, or pre‑specified model covariates; those details were not reported in the source summary.
The protocol describes a 24‑month overall timeline: 18 months allocated to recruitment and follow‑up, and 6 months for close‑out, analysis, and dissemination. The trial is registered under ISRCTN24233750. No specific dissemination plan details (venues, data sharing, or timelines for results reporting) are included in the abstract.
The abstract lists competing interests for several authors. Disclosures include charity‑funded travel grants, investigator‑led funding from device manufacturers, honoraria and speaker fees from multiple pharmaceutical and device companies, and research support from industry. The source names specific relationships for individual investigators; full conflict statements are available in the published article.
Note: This rewritten protocol summary is based only on the information presented in the PubMed/NCBI abstract. Full protocol details, inclusion/exclusion criteria, sample size justification, randomisation procedures, blinding (if any), washout periods, and full statistical analysis plan were not reported in the abstract and therefore are not included here.