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

Small Fiber Neuropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03912220
• Other study ID #: IRB00210072
• Status: Completed
• Phase: Phase 2
• Start date: September 1, 2020
• Est. completion date: May 30, 2023

Study information

• Verified date: June 2024
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: May 30, 2023
• Est. primary completion date: May 1, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Small Fiber Neuropathy

Intervention

Drug:
• Nicotinamide riboside
The experimental arm will investigate the effects of nicotinamide riboside on nerve degeneration and regeneration.
• Placebo Oral Tablet
Placebo drug that looks like the experimental drug, nicotinamide riboside tablets.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Adelson Medical Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Denervation of Skin	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.	2 days
Primary	Reinnervation of Skin	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.	3 months