Microneurographic Assessment of Peripheral Nerves in Healthy Volunteers and Individuals With Sensory Dysfunction Caused by Inherited Mutations in the PIEZO2 Gene
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Firing rate (Hz) in response to fast and slow brushing.
研究概览
简要总结
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.
详细描述
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 (e.g., soft brushing) in PDS patients compared to healthy participants using direct electrical recording from peripheral nerves.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •All Participants
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Male or female, aged 18 years and over.
- •The ability to provide written informed consent.
- •Enrolled in 16-AT-0077, "Clinical and Scientific Assessment of Pain and Painful Disorders".
- •PDS Patients
- •Clinical and genetic diagnosis of PIEZO2-LOF.
- •Healthy participants
- •In good general health as evidenced by medical evaluation under 16-AT-0077.
排除标准
- •All Participants:
- •Difficulties with communication that make subjective innocuous and pain assessments impossible or unreliable.
- •Unable to comply with study procedures or visits.
- •Has a dermatological condition that might influence cutaneous sensitivity.
- •Congenital limb deficiency or amputation of any limb.
- •Prior history of syncope.
- •Peripheral neuropathy or current chronic pain condition or has had chronic pain in the past year (painful condition lasting more than six months), including ongoing treatment with medications for neuropathic pain (e.g. gabapentin, tricyclic antidepressants, pregabalin, tramadol).
- •Has a major medical condition, such as kidney, liver, cardiovascular, autonomic, pulmonary, or neurological problems (e.g., epilepsy) or a chronic systemic disease (e.g., diabetes), or Raynaud's Disease.
- •Current and untreated diagnosis of depression, post-traumatic stress, syndrome, bipolar disorder, psychosis, anxiety or panic disorder, alcohol or substance use disorders.
- •Pregnant (verbal confirmation) or breastfeeding.
- •Are participating in other ongoing research protocols involving interventions that would interfere with somatosensation.
- •Employees or staff that work at NCCIH.
- •Adults who are unable to provide their own consent.
研究组 & 干预措施
PIEZO2 Deficiency Syndrome (PDS)
Participants with a diagnosis of PIEZO2 Deficiency Syndrome; an inherited mutation in the PIEZO2 gene
Healthy controls
Healthy participants
结局指标
主要结局
Firing rate (Hz) in response to fast and slow brushing.
时间窗: At each visit (max of 4 visits) during microneurography procedure.
PDS patients have major deficits in touch detection. Therefore, we predict the response (firing rate) to gentle brush stimuli to be reduced by at least 50% (compared to healthy controls), corresponding to decreased sensitivity to mechanical stimuli. The neural measure of firing rate (Hz) captures both the magnitude of the response and its temporal pattern and has been shown to reliably distinguish between normal and pathological responses and the effects of pharmacological manipulations.
次要结局
- Firing rate (Hz) in response to other sensory modalities, e.g., thermal, and other mechanical stimuli.(At each visit (max of 4 visits) during microneurography procedure.)