Evaluation of Nicotinamide Riboside in Prevention of Small Fiber Axon Degeneration and Promotion of Nerve Regeneration

Phase 2

Completed

Conditions: Small Fiber Neuropathy

Interventions: Drug: Placebo Oral Tablet
Drug: Nicotinamide riboside

Registration Number: NCT03912220

Lead Sponsor: Johns Hopkins University

Brief Summary: This study will evaluate the effects of a nutritional supplement called nicotinamide riboside in preventing small fiber nerve degeneration that is experimentally induced by applying capsaicin to skin in otherwise healthy study participants. Furthermore, the effects on nerve regeneration will also be evaluated. The results will be compared to a placebo control drug.

Detailed Description: Small fiber neuropathy (SFN) is a type of peripheral neuropathy that affects the small unmyelinated fibers, including both somatic innervation of the skin and autonomic nerves. Although diabetes and prediabetes are the two most common causes, up to 50% of all SFN remain idiopathic. Currently there is no effective treatment that prevents it or reverses it through regeneration of nerve fibers.

Recent advances in understanding the molecular machinery that mediates Wallerian degeneration (i.e. degeneration of nerve fibers after physical transection) showed that key molecular players in this pathway and nicotinamide (NAD+) metabolites play a similar role in degeneration of axons in a distal-to-proximal manner seen in many peripheral neuropathies including SFN. Pre-clinical studies have shown that rapid depletion of NAD initiates a cascade of molecular events that leads to axon degeneration and that supplementation of a NAD precursor, nicotinamide riboside (NR) can prevent this degeneration.

In this study investigators plan to evaluate the ability of NR to prevent degeneration of small somatic sensory axons innervating the epidermis as well as its ability to promote regeneration of these same fibers in a human experimental model of nerve degeneration and regeneration. This experimental human model has been used previously to evaluate the rate of nerve degeneration and regeneration in several peripheral neuropathies and in healthy subjects.

Since NR is available as a nutritional supplement, if successful, this research can lead to development of a therapy for a variety of peripheral neuropathies very rapidly.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 45

Inclusion Criteria

Age: 18-65
BMI<32
Normal neurological examination defined as Neuropathy Impairment Score <2

Exclusion Criteria

History of peripheral neuropathy
Any peripheral neuropathy risk factor including diabetes, Vitamin B12 deficiency, HIV-infection, chronic kidney or hepatic disease, hypothyroidism, chemotherapy or other know neurotoxic exposure.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo Oral Tablet	Study participants in the placebo arm will receive placebo pills that are similar in size and shape to the experimental group drug.
Nicotinamide Riboside	Nicotinamide riboside	Experimental group of participants will receive Nicotinamide riboside at a dose of 900 mg twice a day orally.

Primary Outcome Measures

Name	Time	Method
Denervation of Skin	2 days	Examination of degree of loss of intraepidermal nerve fibers in the skin after experimental denervation by capsaicin. The skin biopsies will be stained for a pan-axonal marker and the number of intraepidermal nerve fibers per millimeter (mm) of skin will be counted and compared to baseline skin biopsy to determine the percent change in density of intraepidermal nerve fibers.
Reinnervation of Skin	3 months	Examination of degree of re-innervation of skin after experimental denervation by capsaicin. The skin biopsies will be stained for a pan-axonal marker and the number of intraepidermal nerve fibers per mm of skin will be counted and compared to epidermal nerve fiber density after capsaicin application to determine the median density of intraepidermal nerve fibers.

Secondary Outcome Measures