This paper describes the protocol for a randomized controlled trial testing whether lymphovenous bypass (LVB) combined with standard of care improves small-fiber and autonomic function compared with standard of care alone in diabetic peripheral neuropathy at 6 months.
Diabetic peripheral neuropathy (DPN) is characterized as a length-dependent, symmetric sensorimotor polyneuropathy for which current pharmacologic options are largely symptomatic and do not modify the disease.
Lymphovenous bypass (LVB), a supermicrosurgical procedure established for lymphedema, is hypothesized to modulate lymphatic-immune-microvascular dysfunction relevant to DPN.
The trial is designed as a SPIRIT-aligned, single-center, randomized, controlled, parallel-group superiority trial with a 2:1 allocation ratio (LVB+SOC vs SOC alone).
The primary outcomes are changes in clinical neuropathy burden and pain severity assessed at 6 and 12 months.
The sample size of 60 participants was calculated to provide 80% power to detect a conservative between-group effect size of Cohen d=0.70.
Recruitment commenced in February 2026 and is planned to continue through July 31, 2027, with follow-up through July 31, 2028.
The trial is intended to test a mechanism-based, nonpharmacologic adjunct targeting lymphatic-immune-microvascular dysfunction in DPN, with potential implications for phenotype-directed treatment algorithms.
This paper describes the design and protocol for a clinical trial investigating whether a surgical procedure called lymphovenous bypass (LVB) can help people with diabetic peripheral neuropathy (DPN) — a common and debilitating nerve complication of diabetes that causes pain, numbness, and loss of sensation in the feet and legs. In LVB, tiny connections are surgically created between lymphatic vessels and small veins, a technique already used to treat lymphedema (fluid swelling). The researchers hypothesize that because DPN involves dysfunction in the lymphatic system, immune responses, and tiny blood vessels, LVB might address root causes rather than just masking symptoms as current medications do. The trial will enroll 60 adults with confirmed DPN at a single center. Two-thirds will receive LVB plus standard diabetes and neuropathy care, while one-third will receive standard care alone. The main questions are whether LVB improves nerve function (especially small nerve fibers and the autonomic nervous system), reduces neuropathic pain, and helps heal diabetic foot ulcers, measured at 6 and 12 months. The study uses blinded assessors and rigorous statistical methods and is powered to detect a meaningful difference between groups. As of May 2026, enrollment has just begun with 3 participants, and results are not expected until late 2027 or early 2028. This research suggests that LVB could represent a new, mechanism-based surgical option for diabetic neuropathy if the trial results are positive — filling a significant gap where no current treatment can slow or reverse nerve damage. The trial is still in early stages, and this publication only describes the study plan, not outcomes. If successful, findings could guide more personalized treatment approaches for DPN and prompt larger, multi-site studies.
Lee H, Wang C, Chang T, Chao C, Hsieh S, Cheng N, et al.. (2026). Lymphovenous Bypass as an Adjunct to Standard Care for Diabetic Peripheral Neuropathy: Protocol for a Randomized Assessor-Blinded Superiority Trial.. JMIR research protocols. https://doi.org/10.2196/84826