Assessment of Small Fiber Neuropathy in Rare Diseases Using Sudoscan

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02985710
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arms: 2
• Duration (Months): 48
• Patients Per Site Per Month: 2.1

Study Details

Study Description

Brief Summary

Sudoscan™ (Impeto Medical, Paris France) uses electrochemical skin conductance as a novel noninvasive method to detect sudomotor dysfunction. Several small studies have recently shown that Sudoscan use in the assessment of small fiber polyneuropathy (in diabetes mellitus) can be performed non-invasively, quickly and effectively. The investigators aim to study the use of Sudoscan in rare disease condition associated with small fiber polyneuropathy.

Condition or Disease	Intervention/Treatment	Phase
Small Fiber Neuropathy; Fabry Disease; Ehlers Danlos Syndrome; Mitochondrial Disease	Device: Sudoscan; Procedure: Skin biopsy; Procedure: QSART	N/A

Detailed Description

Small fiber polyneuropathy (SFPN) is diagnosed through a combination of symptoms, signs and confirmatory diagnostic testing. Nerve conduction studies are not sensitive enough in most of the cases leaving the ankle skin biopsy with measurement of intraepidermal nerve fiber density (IENFD) as the main diagnostic tool. Despite its utility and reproducibility, skin biopsy is invasive, expensive and requires a central laboratory for processing and interpretation. Quantitative sudomotor axon reflex testing (QSART) is also routinely used for evaluation of small fiber neuropathy as sudomotor axons can also be involved. This test however remains technically challenging and requires testing conditions in specialized labs that are not always suitable for all patients' population. By comparing findings on skin biopsy and/or QSRT, accepted gold standard for diagnosing SFPN, the investigators seek to find faster, less-invasive ways to diagnose and monitor small-fiber polyneuropathy in rare diseases using Sudoscan measurement.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Assessment of Small Fiber Neuropathy in Rare Diseases Using Sudoscan
• Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Dec 22, 2019
• Actual Study Completion Date: Aug 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Sudoscan only Patients in this arm will only undergoing testing with Sudoscan.	Device: Sudoscan; The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation.
Other: Sudoscan Plus Patients in this arm will get Sudoscan testing as well as a skin biopsy and QSART testing.	Device: Sudoscan; The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation.; Procedure: Skin biopsy; For subjects that give additional consent, skin biopsy will be done in standard fashion under sterile conditions. Assessment of nerve fiber density typically involves a 3-mm punch biopsy of skin from the leg (10 cm above the external malleolus).; Procedure: QSART; QSRT (quantitative sudomotor axon reflex test) testing involves having a technician wipe the subject's arms and leg with alcohol, then tissue to wipe it dry. Electrodes filled with acetylcholine are put on three areas of the leg and one on the wrist, stimulators are turned on and sweat responses are measured.; Other Names: Quantitative Sudomotor Autonomic Reflex Testing

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Abnormal Electrochemical Skin Conductance in the Different Study Groups Who Have Clinical Symptoms Consistent With Small Fiber Polyneuropathy. [12 months]

   The internal software of the Sudoscan will allow analysis of skin conductance in all patients and quantification into normal or abnormal. Correlation of an abnormal conductance measurement with clinical symptoms and signs of small fiber neuropathy will be evaluated for accuracy of Sudoscan measurements

Secondary Outcome Measures

1. Number of Patients in Whom a Specific Skin Conductance (ESC) Signature Pattern Was Detected in the Hands and/or Feet on Sudoscan Measurements. [48 months]

   Distribution of the electrochemical skin conductance (ESC) in both hands and feet was reviewed as an indirect measure of the subject's capacity to sweat. Normative scales of adult sweat function are preloaded in the device and compared to actual measurements to determine if a subject's sweat response is reduced, which is associated with neuropathy. A positive outcome is the identification of a lower ESC in either hands or feet that distinguishes Fabry disease from other disorders and would be a reflection of the presence of SFPN.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Males and females with confirmed disease: Fabry (by GLA enzymes and/or DNA testing) naïve and on ERT, Mitochondrial diseases (electron transport chain and/or DNA testing) or connective tissue diseases (clinical criteria and/or DNA testing when available)

• Consenting adults (18 years and older) who agrees and consents to skin biopsy and QSART procedure

Exclusion Criteria:

• Subjects with cognitive, psychiatric, or other problems that preclude informed consent.

• Patients with history of glucose intolerance or diabetes.

• Patient on chemotherapy

• People with any open or bleeding wounds at any sensor plate contact surface location

• People with any type of implantable device

• People with missing hand(s) and/or leg(s)

• Pregnant women or women who are uncertain about a possible pregnancy

• Patients sensitive to chemicals used to induce sweating

• Patients with heat intolerance

• Patients with bleeding disorders

• Patients on current anticoagulant therapy

• Patients with keloids on the intended biopsy site

• People with hypersensitivity to local amide-type anesthetics

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Amel Karaa, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 20, 2021

More Information

Publications

None provided.

• Responsible Party: Amel Karaa, MD, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02985710
• Other Study ID Numbers: 2015P000205
• First Posted: Dec 7, 2016
• Last Update Posted: Oct 7, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Fabry Disease; Small Fiber Neuropathy; Ehlers-Danlos Syndrome; Mitochondrial Diseases; Rare Diseases

Study Results

Participant Flow

Arm/Group Title	Sudoscan Only	Sudoscan Plus
Arm/Group Description	Patients in this arm will only undergoing testing with Sudoscan. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation.	Patients in this arm will get Sudoscan testing as well as a skin biopsy and QSART testing. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation. Skin biopsy: For subjects that give additional consent, skin biopsy will be done in standard fashion under sterile conditions. Assessment of nerve fiber density typically involves a 3-mm punch biopsy of skin from the leg (10 cm above the external malleolus). QSART: QSRT (quantitative sudomotor axon reflex test) testing involves having a technician wipe the subject's arms and leg with alcohol, then tissue to wipe it dry. Electrodes filled with acetylcholine are put on three areas of the leg and one on the wrist, stimulators are turned on and sweat responses are measured.
Period Title: Overall Study
STARTED	69	33
COMPLETED	65	33
NOT COMPLETED	4	0

Baseline Characteristics

Arm/Group Title	Sudoscan Only	Sudoscan Plus	Total
Arm/Group Description	Patients in this arm will only undergoing testing with Sudoscan. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation.	Patients in this arm will get Sudoscan testing as well as a skin biopsy and QSART testing. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation. Skin biopsy: For subjects that give additional consent, skin biopsy will be done in standard fashion under sterile conditions. Assessment of nerve fiber density typically involves a 3-mm punch biopsy of skin from the leg (10 cm above the external malleolus). QSART: QSRT (quantitative sudomotor axon reflex test) testing involves having a technician wipe the subject's arms and leg with alcohol, then tissue to wipe it dry. Electrodes filled with acetylcholine are put on three areas of the leg and one on the wrist, stimulators are turned on and sweat responses are measured.	Total of all reporting groups
Overall Participants	65	33	98
Age (Count of Participants)
<=18 years	9 13.8%	0 0%	9 9.2%
Between 18 and 65 years	50 76.9%	27 81.8%	77 78.6%
>=65 years	6 9.2%	6 18.2%	12 12.2%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	42.4 (17.02)	43.6 (15.35)	42.5 (16.18)
Sex: Female, Male (Count of Participants)
Female	45 69.2%	22 66.7%	67 68.4%
Male	20 30.8%	11 33.3%	31 31.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 1.5%	0 0%	1 1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	64 98.5%	33 100%	97 99%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	65 100%	33 100%	98 100%
Small fiber polyneuropathy questionnaire (Count of Participants)
Count of Participants [Participants]	51 78.5%	20 60.6%	71 72.4%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Abnormal Electrochemical Skin Conductance in the Different Study Groups Who Have Clinical Symptoms Consistent With Small Fiber Polyneuropathy.
Description	The internal software of the Sudoscan will allow analysis of skin conductance in all patients and quantification into normal or abnormal. Correlation of an abnormal conductance measurement with clinical symptoms and signs of small fiber neuropathy will be evaluated for accuracy of Sudoscan measurements
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sudoscan Only	Sudoscan Plus
Arm/Group Description	Patients in this arm will only undergoing testing with Sudoscan. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation.	Patients in this arm will get Sudoscan testing as well as a skin biopsy and QSART testing. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation. Skin biopsy: For subjects that give additional consent, skin biopsy will be done in standard fashion under sterile conditions. Assessment of nerve fiber density typically involves a 3-mm punch biopsy of skin from the leg (10 cm above the external malleolus). QSART: QSRT (quantitative sudomotor axon reflex test) testing involves having a technician wipe the subject's arms and leg with alcohol, then tissue to wipe it dry. Electrodes filled with acetylcholine are put on three areas of the leg and one on the wrist, stimulators are turned on and sweat responses are measured.
Measure Participants	65	33
Count of Participants [Participants]	42 64.6%	12 36.4%

2. Secondary Outcome

Title	Number of Patients in Whom a Specific Skin Conductance (ESC) Signature Pattern Was Detected in the Hands and/or Feet on Sudoscan Measurements.
Description	Distribution of the electrochemical skin conductance (ESC) in both hands and feet was reviewed as an indirect measure of the subject's capacity to sweat. Normative scales of adult sweat function are preloaded in the device and compared to actual measurements to determine if a subject's sweat response is reduced, which is associated with neuropathy. A positive outcome is the identification of a lower ESC in either hands or feet that distinguishes Fabry disease from other disorders and would be a reflection of the presence of SFPN.
Time Frame	48 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sudoscan Only	Sudoscan Plus
Arm/Group Description	Patients in this arm will only undergoing testing with Sudoscan. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation.	Patients in this arm will get Sudoscan testing as well as a skin biopsy and QSART testing. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation. Skin biopsy: For subjects that give additional consent, skin biopsy will be done in standard fashion under sterile conditions. Assessment of nerve fiber density typically involves a 3-mm punch biopsy of skin from the leg (10 cm above the external malleolus). QSART: QSRT (quantitative sudomotor axon reflex test) testing involves having a technician wipe the subject's arms and leg with alcohol, then tissue to wipe it dry. Electrodes filled with acetylcholine are put on three areas of the leg and one on the wrist, stimulators are turned on and sweat responses are measured.
Measure Participants	65	33
Count of Participants [Participants]	21 32.3%	16 48.5%

Adverse Events

Time Frame	4 years
Adverse Event Reporting Description	This study did not include any intervention that would cause mortality or any serious adverse events.
Arm/Group Title	Sudoscan Only		Sudoscan Plus
Arm/Group Description	Patients in this arm will only undergoing testing with Sudoscan. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation.		Patients in this arm will get Sudoscan testing as well as a skin biopsy and QSART testing. Sudoscan: The Sudoscan is a non invasive procedure and similar to standing on a scale to be weighed. Sudoscan measurements are made in compliance with the manufacturer's recommended procedures. The measurement is rapid and non-invasive, and requires no advance preparation. Skin biopsy: For subjects that give additional consent, skin biopsy will be done in standard fashion under sterile conditions. Assessment of nerve fiber density typically involves a 3-mm punch biopsy of skin from the leg (10 cm above the external malleolus). QSART: QSRT (quantitative sudomotor axon reflex test) testing involves having a technician wipe the subject's arms and leg with alcohol, then tissue to wipe it dry. Electrodes filled with acetylcholine are put on three areas of the leg and one on the wrist, stimulators are turned on and sweat responses are measured.
All Cause Mortality
	Sudoscan Only		Sudoscan Plus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/33 (0%)
Serious Adverse Events
	Sudoscan Only		Sudoscan Plus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Sudoscan Only		Sudoscan Plus
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.