Small Fiber NeuropathyNCT02537951
Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study
A study testing AFI microscope in people with Small Fiber Neuropathy, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
Small fiber neuropathy (SFN) is a common disorder, which has a profound negative impact on quality of life because of severe neuropathic pain. To reliably establish a diagnosis of SFN is challenging, since neurological examination and nerve conduction studies are often normal. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Small Fiber Neuropathy
- What is being tested?
- AFI microscope
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2015to Sep 2016
- Phase
- Interventional
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- healthy volunteers
Who cannot join
- younger than 18 years
- pre-existing neuropathy
- previous allergic reaction to local anaesthetics
Trial locations and contacts
1 site in 1 country.
About this study
Small fiber neuropathy (SFN) is a common disorder, which has a profound negative impact on quality of life because of severe neuropathic pain. To reliably establish a diagnosis of SFN is challenging, since neurological examination and nerve conduction studies are often normal. Autofluorescent flavoprotein imaging (AFI) is an optical method through which neuronal activity in the termination area of small nerve fibers in the spinal cord can be quantified. Since the epidermis also contains a high density of small nerve terminals and since the number of intraepidermal nerve fibers is greatly reduced in patients with SFN, our hypothesis is that AFI intensity is reduced in patients with SFN. To support this hypothesis, a pilot study is required in which the investigators first need to confirm the precision of AFI in the epidermis of the third finger of 10 healthy volunteers. Secondly, lidocaine/prilocaine cream will be used as a negative control. Finally, the AFI signal will be measured after application of a 8% capsaicin patch, through which (temporarily) a selective reduction of small nerve fibers can be induced, mimicking SFN. Using this experimental design, the investigators will be able to test the reliability and validity of AFI for capsaicin-induced small nerve fiber degeneration. This would be a significant step in developing an objective, rapid and non-invasive diagnostic tool to diagnose patients with SFN, which may also be utilized as a biomarker in studies that assess the efficacy of novel treatments for SFN.
Read the detailed description
The first aim of the current project is to test the precision of AFI in the epidermis of 10 healthy volunteers. For this purpose, a range of nociceptive electrical stimuli with increasing intensities (5Hz @ 0.5mA-1.0mA) and one innocuous control stimulus (2000Hz @1mA) will be delivered to the third finger of each subject. The outcome measure is AFI-intensity, which is the change in autofluorescence intensity compared to baseline (delta F/F). The standard deviation of AFI intensity will be the measure of precision. Pearson's correlation coefficient will be calculated between electrical stimulus intensities and AFI intensity. A linear correlation needs to be confirmed, since this is a general characteristic of AFI. A paired t-tests will be performed to compare AFI intensities following 5Hz @ 1mA stimulation and 2000Hz @ 1mA stimulation. Lidocaine/prilocaine cream will be applied to the fingertips of the subjects and the electrical stimuli will be repeated, to serve as a negative control experiment. A repeated-measures ANOVA will be performed to compare AFI intensities before and after application of lidocaine/prilocaine cream.
The second aim of our study is to validate AFI in experimentally induced small nerve fiber degeneration of the epidermis, by comparing AFI intensities in subjects before and one week after application of a 8% capsaicin patch to the third fingertip. A repeated-measures ANOVA will be performed to compare AFI intensities before and after capsaicin-induced small nerve fiber degeneration. Assuming that all subjects develop epidermal small fiber degeneration following the 8% capsaicin patch, a statistically significant difference in AFI intensity would serve as a proof-of-principle and would provide validity to autofluorescent flavoprotein imaging of epidermal nociceptor activity as a diagnostic test for SFN. Comparing the distributions of before and after capsaicin-induced small nerve fiber degeneration will lead to a probability estimation of having SFN based on the outcome measure, i.e. AFI intensity. In future research, false-positive and false-negative consequences will be evaluated, leading to cut-off values in patients suspected for SFN.
- Conditions
- Small Fiber Neuropathy
- Being tested
- AFI microscope, negative control 1: lidocaine/prilocaine, negative control 2: 8% capsaicin
- Keywords
- autofluorescent flavoprotein imaging, capsaicin
- 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.
AFI microscopeDevice
measurement of AFI intensities following increasing nociceptive stimulus intensities
negative control 1: lidocaine/prilocaineDevice
measurement of AFI intensities following lidocaine/prilocaine cream
negative control 2: 8% capsaicinDevice
measurement of AFI intensities following 8% capsaicin patch
| Study group | Role | What they receive |
|---|---|---|
| AFI intensity in healthy volunteers | Experimental | 10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope Receives: Device: AFI microscope |
| negative control 1: lidocaine/prilocaine | Active comparator | 10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope, 1hour after application of lidocaine/prilocaine creme (negative control 1) Receives: Device: negative control 1: lidocaine/prilocaine |
| negative control 2: 8% capsaicin | Active comparator | -10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope, 1week after application of an 8% capsaicin patch (negative control 2) Receives: Device: negative control 2: 8% capsaicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
AFI-intensity After Nociceptive Stimulation
AFI-intensity (delta F/F) at the 3rd fingertip, directly after application of grading nociceptive stimuli
Measured: Day 1, T=0h (AFI measurements), Day 1, T=6h (AFI measurements after lidocaine/prilocaine), Day 7 (AFI measurements after capsaicin)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2015 (estimated)
- Study startSep 2015
- Primary completionJul 2016
- Study completionSep 2016
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 Erasmus Medical CenterThe 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- subjects are first undergoing measurements of AFI intensities following increasing nociceptive stimulus intensities, consequently it is tested whether the AFI activity can be blocked by lidocaine/prilocaine and a 8% capsaicin patch, i.e. whether the AFI activity is specific for nociceptor-acitivity
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joost LM Jongen, Erasmus Medical Center
- Investigators
- Joost LM Jongen, MD, PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02537951
- Sponsor's protocol ID
- NL49568.078.14
- Status last verified
- Feb 2019
- First submitted
- 22 Aug 2015
- Last updated
- 11 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study
- ClinicalTrials.gov ID
- NCT02537951
- Acronym / sponsor ID
- NL49568.078.14
- Conditions
- Small Fiber Neuropathy
- Keywords
- autofluorescent flavoprotein imaging, capsaicin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- Sep 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 2 Sep 2015 (estimated)
- Results
- Posted 3 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Small fiber neuropathy (SFN) is a common disorder, which has a profound negative impact on quality of life because of severe neuropathic pain. To reliably establish a diagnosis of SFN is challenging, since neurological examination and nerve conduction studies are often normal. Autofluorescent flavoprotein imaging (AFI) is an optical method through which neuronal activity in the termination area of small nerve fibers in the spinal cord can be quantified. Since the epidermis also contains a high density of small nerve terminals and since the number of intraepidermal nerve fibers is greatly reduced in patients with SFN, our hypothesis is that AFI intensity is reduced in patients with SFN. To support this hypothesis, a pilot study is required in which the investigators first need to confirm the precision of AFI in the epidermis of the third finger of 10 healthy volunteers. Secondly, lidocaine/prilocaine cream will be used as a negative control. Finally, the AFI signal will be measured after application of a 8% capsaicin patch, through which (temporarily) a selective reduction of small nerve fibers can be induced, mimicking SFN. Using this experimental design, the investigators will be able to test the reliability and validity of AFI for capsaicin-induced small nerve fiber degeneration. This would be a significant step in developing an objective, rapid and non-invasive diagnostic tool to diagnose patients with SFN, which may also be utilized as a biomarker in studies that assess the efficacy of novel treatments for SFN.
Detailed description
The first aim of the current project is to test the precision of AFI in the epidermis of 10 healthy volunteers. For this purpose, a range of nociceptive electrical stimuli with increasing intensities (5Hz @ 0.5mA-1.0mA) and one innocuous control stimulus (2000Hz @1mA) will be delivered to the third finger of each subject. The outcome measure is AFI-intensity, which is the change in autofluorescence intensity compared to baseline (delta F/F). The standard deviation of AFI intensity will be the measure of precision. Pearson's correlation coefficient will be calculated between electrical stimulus intensities and AFI intensity. A linear correlation needs to be confirmed, since this is a general characteristic of AFI. A paired t-tests will be performed to compare AFI intensities following 5Hz @ 1mA stimulation and 2000Hz @ 1mA stimulation. Lidocaine/prilocaine cream will be applied to the fingertips of the subjects and the electrical stimuli will be repeated, to serve as a negative control experiment. A repeated-measures ANOVA will be performed to compare AFI intensities before and after application of lidocaine/prilocaine cream.
The second aim of our study is to validate AFI in experimentally induced small nerve fiber degeneration of the epidermis, by comparing AFI intensities in subjects before and one week after application of a 8% capsaicin patch to the third fingertip. A repeated-measures ANOVA will be performed to compare AFI intensities before and after capsaicin-induced small nerve fiber degeneration. Assuming that all subjects develop epidermal small fiber degeneration following the 8% capsaicin patch, a statistically significant difference in AFI intensity would serve as a proof-of-principle and would provide validity to autofluorescent flavoprotein imaging of epidermal nociceptor activity as a diagnostic test for SFN. Comparing the distributions of before and after capsaicin-induced small nerve fiber degeneration will lead to a probability estimation of having SFN based on the outcome measure, i.e. AFI intensity. In future research, false-positive and false-negative consequences will be evaluated, leading to cut-off values in patients suspected for SFN.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- subjects are first undergoing measurements of AFI intensities following increasing nociceptive stimulus intensities, consequently it is tested whether the AFI activity can be blocked by lidocaine/prilocaine and a 8% capsaicin patch, i.e. whether the AFI activity is specific for nociceptor-acitivity
| Arm | Type | Receives |
|---|---|---|
| AFI intensity in healthy volunteers | Experimental | Device: AFI microscope10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope |
| negative control 1: lidocaine/prilocaine | Active comparator | Device: negative control 1: lidocaine/prilocaine10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope, 1hour after application of lidocaine/prilocaine creme (negative control 1) |
| negative control 2: 8% capsaicin | Active comparator | Device: negative control 2: 8% capsaicin-10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope, 1week after application of an 8% capsaicin patch (negative control 2) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- healthy volunteers
Key exclusion criteria (3 listed)
- younger than 18 years
- pre-existing neuropathy
- previous allergic reaction to local anaesthetics
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 |
|---|---|---|
| AFI microscopemeasurement of AFI intensities following increasing nociceptive stimulus intensities | Device | AFI intensity in healthy volunteers |
| negative control 1: lidocaine/prilocainemeasurement of AFI intensities following lidocaine/prilocaine cream | Device | negative control 1: lidocaine/prilocaine |
| negative control 2: 8% capsaicinmeasurement of AFI intensities following 8% capsaicin patch | Device | negative control 2: 8% capsaicin |
Primary outcome
AFI-intensity After Nociceptive Stimulation
Time frame: Day 1, T=0h (AFI measurements), Day 1, T=6h (AFI measurements after lidocaine/prilocaine), Day 7 (AFI measurements after capsaicin)
AFI-intensity (delta F/F) at the 3rd fingertip, directly after application of grading nociceptive stimuli
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Joost LM Jongen, MD, PhD principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing AFI microscope in people with Small Fiber Neuropathy, run by Erasmus Medical Center at 1 site in Netherlands.
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 1 inclusion and 3 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 11 Jun 2019. 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 Netherlands. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 3 Jun 2019). 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?
AFI-intensity After Nociceptive Stimulation (time frame: Day 1, T=0h (AFI measurements), Day 1, T=6h (AFI measurements after lidocaine/prilocaine), Day 7 (AFI measurements after capsaicin)). 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 11 Jun 2019.