Actively Recruiting

Age: 5Years - 120Years
All Genders
Healthy Volunteers
NCT04394871

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

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

330

Participants Needed

1

Research Sites

524 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Background: Amyotrophic lateral sclerosis type 4 (ALS4) is an inherited motor neuron disease. People with ALS4 have a change in the amount of RNA and DNA that bind together. This binding of RNA with DNA forms units called R-loops. Researchers want to learn how R-loops are related to ALS4. To do this, they will study people with inherited neurological conditions that may affect R-loop levels. These include ALS4, progressive external opthalmoplegia with mitochondrial deletions (PEOB2), Aicardi-Goutieres syndrome (AGS), and ataxia and oculomotor apraxia type 2 (AOA2). Objective: To learn how the binding of RNA with DNA (R-loops) is related to neurological disease. Eligibility: People age 5 and older with ALS4, PEOB2, AGS, and AOA2. Healthy relatives and nonrelatives are also needed. Design: Participants may be screened with a review of x-rays and other medical records. Healthy relative and nonrelative participants will have 1 visit. All other participants will have 4 visits over 3 years. At visits, participants will undergo some or all of the following: Medical history Physical exam Tests of muscle strength and volume and physical function Blood tests Pregnancy test (for some females) Skin biopsy of forearm Magnetic resonance imaging (MRI) Dual x-ray absorptiometry (DEXA). Some tests are optional. The MRI uses a magnetic field and radio waves to take pictures. Participants will lie on a table that slides in and out of the scanner. The scanner makes noise. They will get earplugs. The DEXA scan uses x-rays to take pictures. MRI and DEXA will be used to measure muscle, fat, and lean body mass. ...

CONDITIONS

Official 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 with heterozygous mutation in SETX gene
  • Genetic diagnosis of RNA processing defect mutation such as RNaseH1, RNaseH2, or recessive SETX mutations
  • Family history of RNA processing defect mutation (first, second, or third degree relative)
  • Ability to communicate well and comply with study requirements
  • Capacity to consent (adults) or assent (pediatric subjects) to participate
Not Eligible

You will not qualify if you...

  • Known claustrophobia, pacemaker, ferromagnetic material in body, or other condition preventing MRI
  • Pregnancy
  • Prolonged PT/PTT values (≥3 seconds from upper normal limit), INR ≥1.5, thrombocytopenia (<70,000), abnormal bleeding time or platelet dysfunction
  • History of bleeding disorder
  • Use of anticoagulants
  • Diagnosis of neuromuscular disease or weakness on physical exam (for healthy controls)

AI-Screening

AI-Powered Screening

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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.

CONTACT

C

Christopher Grunseich, M.D.

CONTACT

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

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