Microneurographic Assessment of Peripheral Nerves in Healthy Volunteers and Individuals With Sensory Dysfunction Caused by Inherited Mutations in the PIEZO2 Gene

NCT06052631 | Recruiting

• 2 other identifiers: 10001678001678-AT
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

PIEZO2-Deficiency Syndrome

Keywords

Sensation; TOUCH; Proprioception

Outcome Measures

Primary Outcomes (1)

• Firing rate (Hz) in response to fast and slow brushing.

  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.

  At each visit (max of 4 visits) during microneurography procedure.

Secondary Outcomes (1)

• 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.

Study Arms (2)

Healthy controls

Healthy participants

PIEZO2 Deficiency Syndrome (PDS)

Participants with a diagnosis of PIEZO2 Deficiency Syndrome; an inherited mutation in the PIEZO2 gene

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All participants will be screened and selected from an existing NCCIH protocol, 16-AT-0077. PDS participants will be referred to 16-AT-0077 for screening from an existing NINDS protocol, 12-N-0095.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Center for Complementary and Integrative Health (NCCIH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

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Related Links

• NIH Clinical Center Detailed Web Page

Study Officials

• Miroslav Backonja, M.D.

  National Center for Complementary and Integrative Health (NCCIH)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hayley M Hansen

CONTACT

(301) 451-2026; hayley.hansen@nih.gov

Miroslav Backonja, M.D.

CONTACT

(301) 402-5679; misha.backonja@nih.gov

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 25, 2023
• Study Start (Estimated): May 11, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 6, 2026

Record last verified: 2025-12-29

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)