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

NCT ID: NCT03912220

Last Updated: 2024-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2023-05-30

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.

Conditions

Small Fiber Neuropathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Nicotinamide Riboside

Experimental group of participants will receive Nicotinamide riboside at a dose of 900 mg twice a day orally.

Group Type: EXPERIMENTAL

Nicotinamide riboside

Intervention Type: DRUG

The experimental arm will investigate the effects of nicotinamide riboside on nerve degeneration and regeneration.

Placebo

Study participants in the placebo arm will receive placebo pills that are similar in size and shape to the experimental group drug.

Group Type: PLACEBO_COMPARATOR

Placebo Oral Tablet

Intervention Type: DRUG

Placebo drug that looks like the experimental drug, nicotinamide riboside tablets.

Interventions

Nicotinamide riboside

The experimental arm will investigate the effects of nicotinamide riboside on nerve degeneration and regeneration.

Intervention Type: DRUG

Placebo Oral Tablet

Placebo drug that looks like the experimental drug, nicotinamide riboside tablets.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Adelson Medical Research Foundation

UNKNOWN

Sponsor Role: collaborator

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ahmet Hoke

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins Hospital

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00210072

Identifier Type: -

Identifier Source: org_study_id