Chili peppers, nerve regeneration, and clinical trial design

Distal sensory neuropathies (SN) are common and affect work, sleep, activities of daily living, and quality of life.¹ Despite the frequency of SN it is difficult to determine its causes. SN is the most common neurologic complication of HIV infection.² Glucose dysregulation may cause SN, but the majority of cases are idiopathic.³ Clinical trials of disease-modifying therapies for SN have been largely negative and there are currently no Food and Drug Administration–approved therapies for reversal or slowing of SN progression.

One challenge for testing therapeutic approaches is the limited ability of currently available primary outcome measures such as clinical impairment scales and nerve conduction studies to document functional changes in small caliber sensory nerve fibers that are involved early in SN.⁴ A consequence is that subjects with relatively advanced SN are the focus of clinical trials. Furthermore, as the common forms of SN progress slowly, conventional outcome measures require lengthy studies (on the order of years) to demonstrate efficacy for slowing of progression.⁵

There is thus a need for easily applied and reproducible surrogate …