Ignite Creation Date:
2025-12-24 @ 11:40 PM
Ignite Modification Date:
2026-02-25 @ 7:04 PM
Study NCT ID:
NCT02537951
Status:
COMPLETED
Last Update Posted:
2019-06-11
First Post:
2015-08-22
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000071075', 'term': 'Small Fiber Neuropathy'}], 'ancestors': [{'id': 'D010523', 'term': 'Peripheral Nervous System Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'j.jongen@erasmusmc.nl', 'phone': '+31107041415', 'title': 'Joost L.M. Jongen', 'organization': 'Erasmus MC'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': '1 month', 'eventGroups': [{'id': 'EG000', 'title': 'AFI Intensity in Healthy Volunteers', 'description': '10 healthy volunteers-AFI intensity measurements', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Negative Control 1: Lidocaine/Prilocaine', 'description': '10 healthy volunteers-lidocaine/prilocaine creme, one hour lat', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Negative Control 2: 8% Capsaicin', 'description': '10 healthy volunteers-capsaicin patch (2 hours after lidocaine', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'AFI-intensity After Nociceptive Stimulation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}, {'value': '10', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'AFI Intensity in Healthy Volunteers', 'description': '10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope\n\nAFI microscope: measurement of AFI intensities following increasing nociceptive stimulus intensities'}, {'id': 'OG001', 'title': 'Negative Control 1: Lidocaine/Prilocaine', 'description': '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)\n\nnegative control 1: lidocaine/prilocaine: measurement of AFI intensities following lidocaine/prilocaine cream'}, {'id': 'OG002', 'title': 'Negative Control 2: 8% Capsaicin', 'description': '-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)\n\nnegative control 2: 8% capsaicin: measurement of AFI intensities following 8% capsaicin patch'}], 'classes': [{'categories': [{'measurements': [{'value': '0.60', 'spread': '0.25', 'groupId': 'OG000'}, {'value': '0.25', 'spread': '0.25', 'groupId': 'OG001'}, {'value': '0.50', 'spread': '0.50', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 1, T=0h (AFI measurements), Day 1, T=6h (AFI measurements after lidocaine/prilocaine), Day 7 (AFI measurements after capsaicin)', 'description': 'AFI-intensity (delta F/F) at the 3rd fingertip, directly after application of grading nociceptive stimuli', 'unitOfMeasure': 'unitless', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': '10 Healthy Volunteers', 'description': '10 healthy volunteers underwent three procedures, always in the same order:\n\n1. baseline AFI measurements\n2. application of lidocaine/prilocaine creme, 1 hour later followed by AFI measurements\n3. application of capsaicin patches, 1 week later followed by AFI measurements'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': 'all 10 healthy volunteers underwent 3 experiments, all 10 have completed these experiments:\n\n1. AFI intensity measurements\n2. lidocaine/prilocaine creme, one hour later followed by AFI intensity measurements\n3. capsaicin patch (2 hours after lidocaine/prilocaine creme), one week later followed by AFI intensity measurements'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'AFI Intensity in Healthy Volunteers', 'description': '10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope\n\nAFI microscope: measurement of AFI intensities following increasing nociceptive stimulus intensities\n\nAfter AFI intensity measurements, the same experiment will be repeated one hour after application of lidocaine/prilocaine creme\n\nAfter the negative control experiment using lidocaine/prilocaine creme, AFI intensity measurements will be repeated one week after application of a capsaicin 8% patch (second negative control experiment)'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '25', 'groupId': 'BG000', 'lowerLimit': '20', 'upperLimit': '30'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Netherlands', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2014-06-23', 'size': 244519, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2018-09-29T15:04', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': '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'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-02', 'completionDateStruct': {'date': '2016-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-06-01', 'studyFirstSubmitDate': '2015-08-22', 'resultsFirstSubmitDate': '2018-01-30', 'studyFirstSubmitQcDate': '2015-09-01', 'lastUpdatePostDateStruct': {'date': '2019-06-11', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-02-18', 'studyFirstPostDateStruct': {'date': '2015-09-02', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-06-03', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'AFI-intensity After Nociceptive Stimulation', 'timeFrame': 'Day 1, T=0h (AFI measurements), Day 1, T=6h (AFI measurements after lidocaine/prilocaine), Day 7 (AFI measurements after capsaicin)', 'description': 'AFI-intensity (delta F/F) at the 3rd fingertip, directly after application of grading nociceptive stimuli'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['autofluorescent flavoprotein imaging, capsaicin'], 'conditions': ['Small Fiber Neuropathy']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "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.\n\nThe 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* healthy volunteers\n\nExclusion Criteria:\n\n* younger than 18 years\n* pre-existing neuropathy\n* previous allergic reaction to local anaesthetics'}, 'identificationModule': {'nctId': 'NCT02537951', 'briefTitle': 'Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study', 'organization': {'class': 'OTHER', 'fullName': 'Erasmus Medical Center'}, 'officialTitle': 'Autofluorescent Flavoprotein Imaging of Intraepidermal Nerve Fibers: a Pilot Study', 'orgStudyIdInfo': {'id': 'NL49568.078.14'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'AFI intensity in healthy volunteers', 'description': '10 healthy volunteers, on whose 3rd fingertips AFI intensity is measured through an AFI microscope', 'interventionNames': ['Device: AFI microscope']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'negative control 1: lidocaine/prilocaine', 'description': '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)', 'interventionNames': ['Device: negative control 1: lidocaine/prilocaine']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'negative control 2: 8% capsaicin', 'description': '-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)', 'interventionNames': ['Device: negative control 2: 8% capsaicin']}], 'interventions': [{'name': 'AFI microscope', 'type': 'DEVICE', 'description': 'measurement of AFI intensities following increasing nociceptive stimulus intensities', 'armGroupLabels': ['AFI intensity in healthy volunteers']}, {'name': 'negative control 1: lidocaine/prilocaine', 'type': 'DEVICE', 'description': 'measurement of AFI intensities following lidocaine/prilocaine cream', 'armGroupLabels': ['negative control 1: lidocaine/prilocaine']}, {'name': 'negative control 2: 8% capsaicin', 'type': 'DEVICE', 'description': 'measurement of AFI intensities following 8% capsaicin patch', 'armGroupLabels': ['negative control 2: 8% capsaicin']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3015 CE', 'city': 'Rotterdam', 'country': 'Netherlands', 'facility': 'Dept. Neurology, Erasmus MC', 'geoPoint': {'lat': 51.9225, 'lon': 4.47917}}], 'overallOfficials': [{'name': 'Joost LM Jongen, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Erasmus Medical Center'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Erasmus Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Dr. J.L.M. Jongen, neurologist', 'investigatorFullName': 'Joost LM Jongen', 'investigatorAffiliation': 'Erasmus Medical Center'}}}}