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Trial record 4 of 119 for:    "Neuromuscular Disease" | "Lidocaine"

Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study

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ClinicalTrials.gov Identifier: NCT02537951
Recruitment Status : Completed
First Posted : September 2, 2015
Results First Posted : June 3, 2019
Last Update Posted : June 11, 2019
Sponsor:
Information provided by (Responsible Party):
Joost LM Jongen, Erasmus Medical Center

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Small Fiber Neuropathy Device: AFI microscope Device: negative control 1: lidocaine/prilocaine Device: negative control 2: 8% capsaicin Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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)
Primary Purpose: Diagnostic
Official Title: Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study
Study Start Date : September 2015
Actual Primary Completion Date : July 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: AFI intensity in healthy volunteers
10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope
Device: AFI microscope
measurement of AFI intensities following increasing nociceptive stimulus intensities

Active Comparator: negative control 1: lidocaine/prilocaine
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)
Device: negative control 1: lidocaine/prilocaine
measurement of AFI intensities following lidocaine/prilocaine cream

Active Comparator: 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)
Device: negative control 2: 8% capsaicin
measurement of AFI intensities following 8% capsaicin patch




Primary Outcome Measures :
  1. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • healthy volunteers

Exclusion Criteria:

  • younger than 18 years
  • pre-existing neuropathy
  • previous allergic reaction to local anaesthetics

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02537951


Locations
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Netherlands
Dept. Neurology, Erasmus MC
Rotterdam, Netherlands, 3015 CE
Sponsors and Collaborators
Erasmus Medical Center
Investigators
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Principal Investigator: Joost LM Jongen, MD, PhD Erasmus MC
  Study Documents (Full-Text)

Documents provided by Joost LM Jongen, Erasmus Medical Center:
Study Protocol  [PDF] June 23, 2014


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Responsible Party: Joost LM Jongen, Dr. J.L.M. Jongen, neurologist, Erasmus Medical Center
ClinicalTrials.gov Identifier: NCT02537951     History of Changes
Other Study ID Numbers: NL49568.078.14
First Posted: September 2, 2015    Key Record Dates
Results First Posted: June 3, 2019
Last Update Posted: June 11, 2019
Last Verified: February 2019
Keywords provided by Joost LM Jongen, Erasmus Medical Center:
autofluorescent flavoprotein imaging, capsaicin
Additional relevant MeSH terms:
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Neuromuscular Diseases
Lidocaine
Lidocaine, Prilocaine Drug Combination
Small Fiber Neuropathy
Peripheral Nervous System Diseases
Nervous System Diseases
Prilocaine
Capsaicin
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Anti-Arrhythmia Agents
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Antipruritics
Dermatologic Agents
Anesthetics, Combined