Ignite Creation Date:
2024-05-06 @ 7:33 PM
Last Modification Date:
2024-10-26 @ 3:09 PM
Study NCT ID:
NCT06052631
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-15
First Post:
2023-09-22
Brief Title:
Microneurographic Assessment of Peripheral Nerves in Healthy Volunteers and Individuals With Sensory Dysfunction Caused by Inherited Mutations in the PIEZO2 Gene
Sponsor:
National Center for Complementary and Integrative Health NCCIH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Microneurographic Assessment of Peripheral Nerves in Healthy Volunteers and Individuals With Sensory Dysfunction Caused by Inherited Mutations in the PIEZO2 Gene
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08-29
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
PIEZO2 Deficiency Syndrome PDS is a genetic disorder that affects a person s ability to feel touches and pain Researchers want to know more about how PDS changes nerve function
Objective
To compare nerve function in people with PDS to that in people without PDS
Eligibility
People aged 18 years and older with PDS enrolled in protocol 16-AT-0077 Healthy volunteers are also needed
Design
Participants will have at least 1 clinic visit They will undergo a test that measures activity in the nerves
For the test
Participants will place their arm or leg in a comfortable position
Ultrasound will be used to locate nerves A smooth wand will be slid over the skin to capture images of the structures below
Two thin needles will be inserted through the skin These needles are much smaller than the kind used to draw blood
The needles will record nerve activity as different sensations are applied to the skin These include mild electrical pulses heat and cold bending of the knee or elbow vibration air puffs pulling a hair and tapping stroking brushing stretching pinching and pushing on the skin at different levels of force
Each test takes 5 to 10 minutes Participants will describe the sensations they feel
Participants may opt for an additional test that measures how nerves respond after heat pulses are used to create mild redness on the skin
Researchers would like at least 2 tests from each person Participants may return for up to 3 additional visits if desired to complete all the testing
PIEZO2 Deficiency Syndrome PDS is a genetic disorder that affects a person s ability to feel touches and pain Researchers want to know more about how PDS changes nerve function
Objective
To compare nerve function in people with PDS to that in people without PDS
Eligibility
People aged 18 years and older with PDS enrolled in protocol 16-AT-0077 Healthy volunteers are also needed
Design
Participants will have at least 1 clinic visit They will undergo a test that measures activity in the nerves
For the test
Participants will place their arm or leg in a comfortable position
Ultrasound will be used to locate nerves A smooth wand will be slid over the skin to capture images of the structures below
Two thin needles will be inserted through the skin These needles are much smaller than the kind used to draw blood
The needles will record nerve activity as different sensations are applied to the skin These include mild electrical pulses heat and cold bending of the knee or elbow vibration air puffs pulling a hair and tapping stroking brushing stretching pinching and pushing on the skin at different levels of force
Each test takes 5 to 10 minutes Participants will describe the sensations they feel
Participants may opt for an additional test that measures how nerves respond after heat pulses are used to create mild redness on the skin
Researchers would like at least 2 tests from each person Participants may return for up to 3 additional visits if desired to complete all the testing
Detailed Description:
Study Description
The study aims to characterize peripheral nerve function and physiology in healthy participants and participants with inherited mutations in the PIEZO2 gene otherwise known as PIEZO2- Deficiency Syndrome PDS PIEZO2 encodes a stretch-gated ion channel whose function has been shown to be essential for aspects of gentle touch sensation vibration detection mechanical allodynia and proprioception in humans The physiological effects of PIEZO2 mutations on sensory neurons in humans are unknown The study will improve our understanding of the molecular mechanisms for touch and mechanical pain sensation and determine if the peripheral neurons remain otherwise healthy in the absence of a functioning PIEZO2 channel
Objectives
Primary Objective
To determine whether peripheral neurons have a blunted response to gentle mechanical stimulation eg soft brushing in PDS patients compared to healthy participants using direct electrical recording from peripheral nerves
Secondary Objectives
To examine the physiological properties of different types of mechanically sensitive sensory neurons in response to innocuous and noxious stimuli in PDS patients and healthy participants We expect the loss of PIEZO2 to have greater impact on the responsiveness of certain types mechano-receptor subtypes over others
Endpoints
Primary Endpoint
Our primary endpoint is evidence of reduced responsiveness ie firing rate Hz of peripheral neurons to gentle mechanical brushing stimulation in PDS patients compared to controls We expect a reduction of at least 50 in firing rate Hz
Secondary Endpoints
Our secondary endpoint is the emergence of a differential effect of the loss of PIEZO2 on mechanoreceptor subclasses Mechanoreceptor subclasses will be identified using established criteria eg stimulus sensitivity receptive field size spike morphology and axon conduction velocity The effect of the loss of PIEZO2 on the responsiveness of single-unit subclasses will be quantified by firing rate measures on single-unit data In addition the percept evoked to intraneural electrical stimulation of single-unit subclasses will be noted
The study aims to characterize peripheral nerve function and physiology in healthy participants and participants with inherited mutations in the PIEZO2 gene otherwise known as PIEZO2- Deficiency Syndrome PDS PIEZO2 encodes a stretch-gated ion channel whose function has been shown to be essential for aspects of gentle touch sensation vibration detection mechanical allodynia and proprioception in humans The physiological effects of PIEZO2 mutations on sensory neurons in humans are unknown The study will improve our understanding of the molecular mechanisms for touch and mechanical pain sensation and determine if the peripheral neurons remain otherwise healthy in the absence of a functioning PIEZO2 channel
Objectives
Primary Objective
To determine whether peripheral neurons have a blunted response to gentle mechanical stimulation eg soft brushing in PDS patients compared to healthy participants using direct electrical recording from peripheral nerves
Secondary Objectives
To examine the physiological properties of different types of mechanically sensitive sensory neurons in response to innocuous and noxious stimuli in PDS patients and healthy participants We expect the loss of PIEZO2 to have greater impact on the responsiveness of certain types mechano-receptor subtypes over others
Endpoints
Primary Endpoint
Our primary endpoint is evidence of reduced responsiveness ie firing rate Hz of peripheral neurons to gentle mechanical brushing stimulation in PDS patients compared to controls We expect a reduction of at least 50 in firing rate Hz
Secondary Endpoints
Our secondary endpoint is the emergence of a differential effect of the loss of PIEZO2 on mechanoreceptor subclasses Mechanoreceptor subclasses will be identified using established criteria eg stimulus sensitivity receptive field size spike morphology and axon conduction velocity The effect of the loss of PIEZO2 on the responsiveness of single-unit subclasses will be quantified by firing rate measures on single-unit data In addition the percept evoked to intraneural electrical stimulation of single-unit subclasses will be noted
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 001678-AT | None | None | None |