Lymphovenous Bypass as an Adjunct to Standard Care for Diabetic Peripheral Neuropathy: Protocol for a Randomized Assessor-Blinded Superiority Trial
Bibliographic record
Abstract
Abstract Background Diabetic peripheral neuropathy (DPN) is a length-dependent, symmetric sensorimotor polyneuropathy with a substantial global and regional burden. Current pharmacologic options are largely symptomatic and do not modify the disease. Lymphovenous bypass (LVB), a supermicrosurgical procedure established for lymphedema, may modulate lymphatic-immune-microvascular dysfunction relevant to DPN. Objective The primary objective is to determine whether LVB combined with standard of care (SOC) improves small-fiber and autonomic function compared with SOC alone at 6 months. Secondary objectives are to evaluate the effects of LVB on large-fiber function, neuropathic pain, ulcer healing, quality of life, and relevant biomarkers, as well as to characterize the safety profile of LVB. Methods This is a SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials)–aligned, single-center, randomized, controlled, parallel-group superiority trial with a 2:1 allocation (LVB+SOC vs SOC alone). Randomization is stratified based on the presence or absence of active diabetic foot ulcers, as defined by the International Working Group on the Diabetic Foot and Infectious Diseases Society of America criteria. In total, 60 adults aged 20 to 80 years with confirmed DPN will be enrolled. LVB involves lymphatic-venous anastomosis to venules ≤0.8 mm. SOC consists of guideline-based glycemic and risk-factor management, pain control, and standardized wound care. Outcome assessors and statisticians are blinded. The primary outcomes are changes in clinical neuropathy burden and pain severity at 6 and 12 months. Secondary outcomes comprise objective measures of somatic and autonomic physiology, histopathological nerve fiber density, biological serum markers, and longitudinal ulcer epithelialization parameters. Data analysis will use mixed-effects models for repeated measures, with a sample size of 60 adults providing 80% power to detect a conservative between-group effect size of Cohen d =0.70. Results Recruitment commenced in February 2026 and is planned to continue through July 31, 2027, with follow-up through July 31, 2028. As of May 2026, we have enrolled 3 participants. The first participant has been treated, and a second participant is scheduled to undergo treatment. Data analysis and reporting are anticipated between late 2027 and early 2028. No outcome data are included. Conclusions This trial tests a mechanism-based, nonpharmacologic adjunct targeting lymphatic-immune-microvascular dysfunction in DPN. If effective, LVB could inform phenotype-directed treatment algorithms and motivate multicenter evaluation and health economic analyses.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.026 | 0.028 |
| Meta-epidemiology (narrow) | 0.005 | 0.002 |
| Meta-epidemiology (broad) | 0.007 | 0.005 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.003 | 0.003 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.005 | 0.007 |
| Insufficient payload (model declined to judge) | 0.079 | 0.013 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".