Actively Recruiting

Age: 5Years - 120Years
All Genders
Healthy Volunteers
ID04394871

An Observational Study to Assess Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4, Other Inherited Neurological Disorders With RNA Processing Defects, and Other Neurological Diseases With a Gain of Function Mechanism

Led by National Institute of Neurological Disorders and Stroke (NINDS) ยท Updated on 2025-11-28

330

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are studying Amyotrophic Lateral Sclerosis Type 4 (ALS4), an inherited motor neuron disease caused by mutations in the senataxin (SETX) gene, along with other inherited neurological disorders involving RNA processing defects and gain of function mutations. The goal is to understand how RNA-DNA binding units called R-loops relate to disease progression and to identify clinical and molecular biomarkers. These biomarkers may help evaluate future treatments for ALS4 and similar neurological diseases. Participants in this observational study include those with ALS4, other RNA metabolism disorders, gain of function mutations, and healthy control groups. The study involves annual visits over 3 years for ALS4 and disease control participants, and up to 5 years for the gain of function group, with one visit for healthy controls. Evaluations include medical history, physical exams, muscle strength tests, blood tests, skin biopsies, MRI scans, and DEXA scans to measure muscle and body composition. During the study, participants will undergo various assessments such as neuromuscular ultrasound, functional tests like the 6-minute walk, and questionnaires about health and function. Researchers will monitor disease progression using thigh muscle volume and other measures annually. Some tests are optional, and safety monitoring includes pregnancy tests when applicable. Total involvement varies by group, with up to 4 visits over 3 years or up to 11 visits over 5 years, depending on the cohort.

CONDITIONS

Brief Title

Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4 and Other Inherited Neurological Disorders of RNA Processing

Who Can Participate

Age: 5Years - 120Years
All Genders
Healthy Volunteers

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 5 years or older
  • Genetic diagnosis of ALS4 (heterozygous mutation in SETX) for ALS4 RNA metabolism group
  • Genetic diagnosis of RNA processing defect mutation (e.g., RNaseH1, RNaseH2, recessive SETX mutations) for disease control group
  • Family history of RNA processing defect mutation for related healthy controls
  • Ability to communicate well and understand study requirements
  • Capacity to consent (adults) or assent (pediatric subjects) to the study
  • Genetic diagnosis of gain of function mutation for gain of function group
  • Healthy unrelated volunteers age 5 or older able to communicate and consent/assent
Not Eligible

You will not qualify if you...

  • Known claustrophobia or presence of pacemaker or ferromagnetic material preventing MRI
  • Pregnancy
  • Diagnosis of neuromuscular disease or weakness on physical exam for healthy controls
  • Prolonged blood clotting times (PT/PTT), abnormal INR, thrombocytopenia, bleeding disorders, or use of anticoagulants excluding lumbar puncture procedure
  • Other conditions preventing safe MRI or study participation

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Monitoring

Duration - Up to 3 years

Participants with inherited RNA metabolism mutations and disease controls will be evaluated annually to collect clinical and molecular biomarkers to understand disease progression.

4 visits, approximately 1 visit every 12 months

Monitoring

Duration - Up to 5 years

Participants with gain of function mutations will be evaluated periodically to collect clinical and molecular biomarkers to understand disease progression.

Up to 11 visits no more frequent than every 6 months

Surveillance

Duration - Single visit

Healthy control participants will have a single visit to collect clinical and molecular biomarkers for comparison purposes.

1 visit (in-person or offsite for related controls)

Trial Site Locations

Total: 1 location

1

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Actively Recruiting

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Research Team

A

Angela D Kokkinis, R.N.

C

Christopher Grunseich, M.D.

How is the study designed?

Study Type

OBSERVATIONAL

Masking

N/A

Allocation

N/A

Model

N/A

Primary Purpose

N/A

Number of Arms

5

Frequently Asked Questions

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Published Research Related To This Trial

Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters.

Christopher Grunseich, Isabel X Wang, Jason A Watts...

https://pubmed.ncbi.nlm.nih.gov/29395064