Small Fiber NeuropathyPhase 2NCT03912220
Evaluation of Nicotinamide Riboside in Prevention of Small Fiber Axon Degeneration and Promotion of Nerve Regeneration
A Phase 2 study testing Nicotinamide riboside in people with Small Fiber Neuropathy, run by Johns Hopkins University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Small Fiber Neuropathy
- What is being tested?
- Nicotinamide riboside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2020to 30 May 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Age: 18-65
- BMI<32
- Normal neurological examination defined as Neuropathy Impairment Score <2
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Nicotinamide riboside, Placebo Oral Tablet
- Medical subject headings
- Small Fiber Neuropathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide ribosideDrug
The experimental arm will investigate the effects of nicotinamide riboside on nerve degeneration and regeneration.
Placebo Oral TabletDrug
Placebo drug that looks like the experimental drug, nicotinamide riboside tablets.
| Study group | Role | What they receive |
|---|---|---|
| Nicotinamide Riboside | Experimental | Experimental group of participants will receive Nicotinamide riboside at a dose of 900 mg twice a day orally. Receives: Drug: Nicotinamide riboside |
| Placebo | Placebo comparator | Study participants in the placebo arm will receive placebo pills that are similar in size and shape to the experimental group drug. Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 days
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.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2019
- Study start1 Sep 2020
- Primary completion1 May 2023
- Study completion30 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Fiber NeuropathyStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Adelson Medical Research Foundation
- Responsible party
- Sponsor
- Investigators
- Ahmet Hoke, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03912220
- Sponsor's protocol ID
- IRB00210072
- Status last verified
- Jun 2024
- First submitted
- 9 Apr 2019
- Last updated
- 12 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Nicotinamide Riboside in Prevention of Small Fiber Axon Degeneration and Promotion of Nerve Regeneration
- ClinicalTrials.gov ID
- NCT03912220
- Acronym / sponsor ID
- IRB00210072
- Conditions
- Small Fiber Neuropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Adelson Medical Research Foundation
- Study start
- 1 Sep 2020 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 11 Apr 2019 (actual)
- Results
- Posted 6 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Nicotinamide Riboside | Experimental | Drug: Nicotinamide ribosideExperimental group of participants will receive Nicotinamide riboside at a dose of 900 mg twice a day orally. |
| Placebo | Placebo comparator | Drug: Placebo Oral TabletStudy participants in the placebo arm will receive placebo pills that are similar in size and shape to the experimental group drug. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age: 18-65
- BMI<32
- Normal neurological examination defined as Neuropathy Impairment Score <2
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotinamide ribosideThe experimental arm will investigate the effects of nicotinamide riboside on nerve degeneration and regeneration. | Drug | Nicotinamide Riboside |
| Placebo Oral TabletPlacebo drug that looks like the experimental drug, nicotinamide riboside tablets. | Drug | Placebo |
Primary outcome
Denervation of Skin
Time frame: 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
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Small Fiber Neuropathy
Recruiting
Evaluation of the Prevalence, and Immunological Characteristics of Small Fiber Neuropathy in Patients With Primary Sjögren's Syndrome
Sjögren's Syndrome, Small Fiber Neuropathy
Recruiting
Magnetic Brain Stimulation in Small Fiber Neuropathy
Small Fiber Neuropathy
Recruiting
Spinal Cord Stimulation and Small Fiber Peripheral Neuropathy
Diabetic Peripheral Neuropathy
Not yet recruitingPhase 4
Effect of Tirzepatide on Diabetic Peripheral Sensorimotor Neuropathy
Neuropathy, Small Fiber, Diabete Mellitus
Enrolling by invitation
Pilot Study to Evaluate Changes in Intra-Epidermal Nerve Fiber Density (IENFD) in Patients With Small-Fiber Neuropathy
Small Fiber Neuropathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmet Hoke principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicotinamide riboside in people with Small Fiber Neuropathy, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Denervation of Skin (time frame: 2 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2024.