Is Nerve Electrophysiology a Robust Primary Endpoint in Clinical Trials of Treatments for Diabetic Peripheral Neuropathy?


Al-Bazz, Dalal Y, Nelson, Andrew J, Burgess, Jamie ORCID: 0000-0002-7165-6918, Petropoulos, Ioannis N, Nizza, Jael, Marshall, Anne ORCID: 0000-0002-2331-3750, Brown, Emily, Cuthbertson, Daniel J ORCID: 0000-0002-6128-0822, Marshall, Andrew G ORCID: 0000-0001-8273-7089, Malik, Rayaz A et al (show 1 more authors) (2022) Is Nerve Electrophysiology a Robust Primary Endpoint in Clinical Trials of Treatments for Diabetic Peripheral Neuropathy? DIAGNOSTICS, 12 (3). 731-. ISSN 2075-4418, 2075-4418

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Abstract

There is currently no FDA-approved disease-modifying therapy for diabetic peripheral neuropathy (DPN). Nerve conduction velocity (NCV) is an established primary endpoint of disease-modifying therapies in DPN and clinical trials have been powered with an assumed decline of 0.5 m/s/year. This paper sought to establish the time-dependent change in NCV associated with a placebo, compared to that observed in the active intervention group. A literature search identified twenty-one double-blind, randomised controlled trials in DPN of ≥1 year duration conducted between 1971 and 2021. We evaluated changes in neurophysiology, with a focus on peroneal motor and sural sensory NCV and amplitude in the placebo and treatment groups. There was significant variability in the change and direction of change (reduction/increase) in NCV in the placebo arm, as well as variability influenced by the anatomical site of neurophysiological measurement within a given clinical trial. A critical re-evaluation of efficacy trials should consider placebo-adjusted effects and present the placebo-subtracted change in NCV rather than assume a universal annual decline of 0.5 m/s/year. Importantly, endpoints such as corneal confocal microscopy (CCM) have demonstrated early nerve repair, whilst symptoms and NCV have not changed, and should thus be considered as a viable alternative.

Item Type: Article
Uncontrolled Keywords: nerve electrophysiology, peripheral neuropathy, diabetes
Divisions: Faculty of Health & Life Sciences
Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 06 Apr 2022 14:03
Last Modified: 22 May 2026 19:47
DOI: 10.3390/diagnostics12030731
Open Access URL: https://doi.org/10.3390/diagnostics12030731
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3152286
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