The Natural History of TRPV4 Neuropathy

NCT05600764 | Recruiting

• 1 other identifier: IRB00341314
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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. Participation requires annual study visits at Johns Hopkins for adult and juvenile participants.

Conditions

TRPV4 Gene Mutation

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  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).

  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.

  Annually for 6 years

Eligibility Criteria

• Age: 3 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Muscular Dystrophy Association: collaborator
• Actio Biosciences, Inc.: collaborator

Study Sites (1)

Johns Hopkins

Baltimore, Maryland, 21287, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood and urine samples will be taken at each study visit.

Study Officials

• Charlotte Sumner, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Betty Hu

CONTACT

443-250-4699; xhu38@jhu.edu

Simone Thomas

CONTACT

(410) 614-4188; sthom125@jhmi.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 6 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: October 31, 2022
• Study Start: December 15, 2023
• Primary Completion (Estimated): December 1, 2033
• Study Completion (Estimated): December 1, 2048
• Last Updated: November 4, 2025

Record last verified: 2025-11

Locations

US (1)