TRPV4 Gene MutationNCT05600764
The Natural History of TRPV4 Neuropathy
An observational study of TRPV4 Gene Mutation, run by Johns Hopkins University at 1 site in United States.
Trial summary
The goal of this research is to document the natural history of neuropathy in patients with a confirmed genetic mutation in the TRPV4 gene. The investigators are searching for patients willing to participate in a 6-year long study to document the symptoms of TRPV4-associated disease and their progression over time. Read more about this study
- Who is it for?
- Ages 3 to 80 years
- Conditions the study is for
- TRPV4 Gene Mutation
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Dec 2023to Dec 2048
- How long will I take part?
- 6 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Juveniles and adults with a confirmed genetic mutation in the transient receptor potential cation channel subfamily V member 4 (TRPV4) gene and clinical symptoms consistent with TRPV4-associated disease which can be known as Charcot-Marie-Tooth disease 2C, scapuloperoneal spinal muscular atrophy, or congenital distal spinal muscular atrophy.
Who may be able to join
- Patient is aged 3-80 years with a documented mutation in the TRPV4 gene and a clinical phenotype consistent with TRPV4-associated disease (as determined by the investigator) OR
- The patient has a first-degree relative (parent, child, sibling, half-sibling, aunt, uncle, grandparent, or grandchild) with a documented disease-causing mutation AND a clear link between that family member and the affected patient AND a clinical phenotype consistent with TRPV4-associated disease.
- Patients with a variant of unknown significance in TRPV4 and a clinical phenotype possibly consistent with TRPV4-associated disease will be eligible for initial enrolment, but continued eligibility will be determined based on whether the observed clinical phenotype is consistent with TRPV4-associated disease (as determined by the investigator).
- Participant or legal guardian for patients under 18 years of age is capable of giving signed informed consent.
Who cannot join
- Medical history of other concomitant neurological disease or clinically significant physical exam/laboratory result that, in the opinion of the investigator, would render the patient being unsuitable for the study.
- Patients with a TRPV4 variant of unknown significance who are initially enrolled but then deemed to be unlikely to have a phenotype consistent with TRPV4-associated disease will no longer be eligible and their clinical data will be deleted.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Johns Hopkins
Baltimore, Maryland, 21287
Betty Hu, 410-502-2705, xhu38@jhu.edu
About this study
The goal of this research is to document the natural history of neuropathy in patients with a confirmed genetic mutation in the TRPV4 gene. The investigators are searching for patients willing to participate in a 6-year long study to document the symptoms of TRPV4-associated disease and their progression over time. Participation requires annual study visits at Johns Hopkins for adult and juvenile participants.
Read the detailed description
Genetic variants in the transient receptor potential cation channel subfamily V member 4 (TRPV4) gene are known to cause different forms of inherited neuropathy that can manifest with muscle weakness, sensory loss, and problems with the vocal cords. These different conditions can be referred to as Charcot-Marie-Tooth disease 2C, scapuloperoneal spinal muscular atrophy, or congenital distal spinal muscular atrophy. For unclear reasons, the symptoms vary significantly among the patients, from mild to severe impact and from early childhood onset to adult onset. Research has shown that disease-causing changes in the TRPV4 gene cause overactivation of TRPV4, which could theoretically be treated with a TRPV4 blocking drug.
There have been many case reports about patients with TRPV4-associated disease, but never has there been a large cohort evaluation to study the natural history of the disease to document the frequency and severity of symptoms and how they change over time. Understanding the different sub-types of disease and how they progress over time is essential knowledge to design clinical trials to evaluate the effectiveness of potential treatments.
The investigators are therefore seeking patients with a confirmed mutation in the TRPV4-gene to participate in this research project. It requires annual study visits at Johns Hopkins (Baltimore, Maryland) for adults and pediatric participants. The study is designed to follow patients for six years and testing is scheduled to occur over two days for each visit. Participants will be reimbursed for travel expenses and hotel accommodations, and all tests will be performed free of charge.
Planned testing includes thorough neurological exams, nerve conduction studies, standardized questionnaires, brain MRIs, skeletal X-rays and bone density scans (DEXA), vocal cord and voice assessments, retinal (eye) scans, and a series of tests to evaluate the ability to perform tasks of daily living such as getting up from a chair or walking for six minutes. The investigators will also collect blood samples from each participant to be used for laboratory research.
- Conditions
- TRPV4 Gene Mutation
What is being measured
The primary outcome is the main question the study is designed to answer.
Tracking the severity of overall neuropathy symptoms
The Charcot Marie Tooth neuropathy score (CMTNS) which is an overall score that incorporates the sub-scores of Charcot Marie Tooth exam score (CMTES) and the Charcot Marie Tooth symptom score (CMTSS) which are all assessed at once. The minimum score is 0, the maximum score is 20, and higher scores indicate more severe disease.
Measured: Annually for 6 years
Tracking the progression of the disease using functional measures
The Charcot Marie Tooth functional outcome measure (CMT-FOM) uses a variety of functional tests and questions about symptoms to measure the disease progression of the neuropathy. The minimum score is 0, the maximum score is 52, and higher scores indicate more severe disease.
Measured: Annually for 6 years
Tracking the severity of limitations caused by neuropathy
The Overall Neuropathy Limitations Scale (ONLS) tracks how patients are limited by their neuropathy in certain tasks and movements. The scale goes from 0 (meaning no disability) to 12 (meaning maximum disability).
Measured: Annually for 6 years
Tracking the severity of disease in pediatric patients
The Charcot Marie Tooth pediatric scale (CMTPeds) will be used for patients between 4 and 18 years of age. The minimum score is 0, the maximum score is 44, and higher scores indicate more severe disease.
Measured: Annually for 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2022
- Study start15 Dec 2023
- Primary completionDec 2033 (estimated)
- Study completionDec 2048 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TRPV4 Gene MutationStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
- Target duration
- 6 Years
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Muscular Dystrophy Association, Actio Biosciences, Inc.
- Responsible party
- Sponsor
- Investigators
- Charlotte Sumner, MD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05600764
- Sponsor's protocol ID
- IRB00341314
- Status last verified
- Nov 2025
- First submitted
- 27 Oct 2022
- Last updated
- 4 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Natural History of TRPV4 Neuropathy
- ClinicalTrials.gov ID
- NCT05600764
- Acronym / sponsor ID
- IRB00341314
- Conditions
- TRPV4 Gene Mutation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- Muscular Dystrophy Association, Actio Biosciences, Inc.
- Study start
- 15 Dec 2023 (actual)
- Primary completion
- Dec 2033 (estimated)
- Study completion
- Dec 2048 (estimated)
- First posted
- 31 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this research is to document the natural history of neuropathy in patients with a confirmed genetic mutation in the TRPV4 gene. The investigators are searching for patients willing to participate in a 6-year long study to document the symptoms of TRPV4-associated disease and their progression over time. Participation requires annual study visits at Johns Hopkins for adult and juvenile participants.
Detailed description
Genetic variants in the transient receptor potential cation channel subfamily V member 4 (TRPV4) gene are known to cause different forms of inherited neuropathy that can manifest with muscle weakness, sensory loss, and problems with the vocal cords. These different conditions can be referred to as Charcot-Marie-Tooth disease 2C, scapuloperoneal spinal muscular atrophy, or congenital distal spinal muscular atrophy. For unclear reasons, the symptoms vary significantly among the patients, from mild to severe impact and from early childhood onset to adult onset. Research has shown that disease-causing changes in the TRPV4 gene cause overactivation of TRPV4, which could theoretically be treated with a TRPV4 blocking drug.
There have been many case reports about patients with TRPV4-associated disease, but never has there been a large cohort evaluation to study the natural history of the disease to document the frequency and severity of symptoms and how they change over time. Understanding the different sub-types of disease and how they progress over time is essential knowledge to design clinical trials to evaluate the effectiveness of potential treatments.
The investigators are therefore seeking patients with a confirmed mutation in the TRPV4-gene to participate in this research project. It requires annual study visits at Johns Hopkins (Baltimore, Maryland) for adults and pediatric participants. The study is designed to follow patients for six years and testing is scheduled to occur over two days for each visit. Participants will be reimbursed for travel expenses and hotel accommodations, and all tests will be performed free of charge.
Planned testing includes thorough neurological exams, nerve conduction studies, standardized questionnaires, brain MRIs, skeletal X-rays and bone density scans (DEXA), vocal cord and voice assessments, retinal (eye) scans, and a series of tests to evaluate the ability to perform tasks of daily living such as getting up from a chair or walking for six minutes. The investigators will also collect blood samples from each participant to be used for laboratory research.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 6 Years
Who may qualify
- Ages
- 3 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Juveniles and adults with a confirmed genetic mutation in the transient receptor potential cation channel subfamily V member 4 (TRPV4) gene and clinical symptoms consistent with TRPV4-associated disease which can be known as Charcot-Marie-Tooth disease 2C, scapuloperoneal spinal muscular atrophy, or congenital distal spinal muscular atrophy.
Key inclusion criteria (4 listed)
- Patient is aged 3-80 years with a documented mutation in the TRPV4 gene and a clinical phenotype consistent with TRPV4-associated disease (as determined by the investigator) OR
- The patient has a first-degree relative (parent, child, sibling, half-sibling, aunt, uncle, grandparent, or grandchild) with a documented disease-causing mutation AND a clear link between that family member and the affected patient AND a clinical phenotype consistent with TRPV4-associated disease.
- Patients with a variant of unknown significance in TRPV4 and a clinical phenotype possibly consistent with TRPV4-associated disease will be eligible for initial enrolment, but continued eligibility will be determined based on whether the observed clinical phenotype is consistent with TRPV4-associated disease (as determined by the investigator).
- Participant or legal guardian for patients under 18 years of age is capable of giving signed informed consent.
Key exclusion criteria (2 listed)
- Medical history of other concomitant neurological disease or clinically significant physical exam/laboratory result that, in the opinion of the investigator, would render the patient being unsuitable for the study.
- Patients with a TRPV4 variant of unknown significance who are initially enrolled but then deemed to be unlikely to have a phenotype consistent with TRPV4-associated disease will no longer be eligible and their clinical data will be deleted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Tracking the severity of overall neuropathy symptoms
Time frame: Annually for 6 years
The Charcot Marie Tooth neuropathy score (CMTNS) which is an overall score that incorporates the sub-scores of Charcot Marie Tooth exam score (CMTES) and the Charcot Marie Tooth symptom score (CMTSS) which are all assessed at once. The minimum score is 0, the maximum score is 20, and higher scores indicate more severe disease.
Tracking the progression of the disease using functional measures
Time frame: Annually for 6 years
The Charcot Marie Tooth functional outcome measure (CMT-FOM) uses a variety of functional tests and questions about symptoms to measure the disease progression of the neuropathy. The minimum score is 0, the maximum score is 52, and higher scores indicate more severe disease.
Tracking the severity of limitations caused by neuropathy
Time frame: Annually for 6 years
The Overall Neuropathy Limitations Scale (ONLS) tracks how patients are limited by their neuropathy in certain tasks and movements. The scale goes from 0 (meaning no disability) to 12 (meaning maximum disability).
Tracking the severity of disease in pediatric patients
Time frame: Annually for 6 years
The Charcot Marie Tooth pediatric scale (CMTPeds) will be used for patients between 4 and 18 years of age. The minimum score is 0, the maximum score is 44, and higher scores indicate more severe disease.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Charlotte Sumner, MD principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of TRPV4 Gene Mutation, run by Johns Hopkins University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Betty Hu (443-250-4699, xhu38@jhu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tracking the severity of overall neuropathy symptoms (time frame: Annually for 6 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2025.