Ehlers Danlos Syndrome, Fabry Disease, Mitochondrial Disease, Small Fiber Neuropathy
Conditions
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.
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.
Interventions
DEVICESudoscan
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.
PROCEDURESkin 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).
PROCEDUREQSART
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.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sudoscan Only 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. | 65 |
| Sudoscan Plus 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. | 33 |
| Total | 98 |
Baseline characteristics
| Characteristic | Sudoscan Only | Sudoscan Plus | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 9 Participants | 0 Participants | 9 Participants |
| Age, Categorical >=65 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 27 Participants | 77 Participants |
| Age, Continuous | 42.4 years STANDARD_DEVIATION 17.02 | 43.6 years STANDARD_DEVIATION 15.35 | 42.5 years STANDARD_DEVIATION 16.18 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 64 Participants | 33 Participants | 97 Participants |
| Region of Enrollment United States | 65 Participants | 33 Participants | 98 Participants |
| Sex: Female, Male Female | 45 Participants | 22 Participants | 67 Participants |
| Sex: Female, Male Male | 20 Participants | 11 Participants | 31 Participants |
| Small fiber polyneuropathy questionnaire | 51 Participants | 20 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 65 | 0 / 33 |
| other Total, other adverse events | 0 / 65 | 0 / 33 |
| serious Total, serious adverse events | 0 / 65 | 0 / 33 |
Outcome results
Primary
Number of Patients With Abnormal Electrochemical Skin Conductance in the Different Study Groups Who Have Clinical Symptoms Consistent With Small Fiber Polyneuropathy.
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sudoscan Only | Number of Patients With Abnormal Electrochemical Skin Conductance in the Different Study Groups Who Have Clinical Symptoms Consistent With Small Fiber Polyneuropathy. | 42 Participants |
| Sudoscan Plus | Number of Patients With Abnormal Electrochemical Skin Conductance in the Different Study Groups Who Have Clinical Symptoms Consistent With Small Fiber Polyneuropathy. | 12 Participants |
Secondary
Number of Patients in Whom a Specific Skin Conductance (ESC) Signature Pattern Was Detected in the Hands and/or Feet on Sudoscan Measurements.
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sudoscan Only | Number of Patients in Whom a Specific Skin Conductance (ESC) Signature Pattern Was Detected in the Hands and/or Feet on Sudoscan Measurements. | 21 Participants |
| Sudoscan Plus | Number of Patients in Whom a Specific Skin Conductance (ESC) Signature Pattern Was Detected in the Hands and/or Feet on Sudoscan Measurements. | 16 Participants |