An Observational Study to Assess Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4 and Other Inherited Neurological Disorders of RNA Processing

Study Purpose:

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).

Disease:

Familial ALS

Study Type:

Observational Study

Study Category:

Biomarkers/Imaging

Study Status:

Enrolling

Phase:

Not Applicable

Study Chair(s)/Principal Investigator(s):

Christopher Grunseich, M.D. National Institute of Neurological Disorders and Stroke (NINDS)

Clinicaltrials.gov ID (11 digit #):

NCT04394871

Neals Affiliated?

No

Coordinating Center Contact Information

National Institutes of Health Clinical Center
Angela Kokkinis, R.N. / .(JavaScript must be enabled to view this email address) / 301-451-8146
.(JavaScript must be enabled to view this email address) Bethesda, Maryland 20892 United States

Full Study Summary:

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.

Study Sponsor:

National Institute of Neurological Disorders and Stroke (NINDS)

Participant Duration:

Estimated Enrollment:

315

Estimated Study Start Date:

06/26/2020

Estimated Study Completion Date:

12/31/2025

Posting Last Modified Date:

06/23/2020

Date Study Added to alsconsortium.org:

06/23/2020
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    5

    Maximum Age:

    N/A

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?


    INCLUSION CRITERIA

    ALS4 inclusion criteria:

    • Age 5 or above
    • Genetic diagnosis of ALS4 (heterozygous mutation in SETX)
    • Able to communicate well with the investigator, to understand and comply with the requirements of the study
    • Capacity to consent (adults) or assent (pediatric subjects) to the study

    Disease control inclusion criteria:

    • Age 5 or above
    • Genetic diagnosis of RNA processing defect mutation (RNaseH1, RNaseH2, recessive mutations in SETX)
    • Able to communicate well with the investigator, to understand and comply with the requirements of the study
    • Capacity to consent (adults) or assent (pediatric subjects) to the study

    Related, unaffected healthy control inclusion criteria:

    • Age 5 or above
    • Family history (first, second, or third degree relative) of RNA processing defect mutation (RNaseH1, RNaseH2, heterozygous or recessive mutations in SETX)
    • Able to communicate well with the investigator, to understand and comply with the requirements of the study
    • Capacity to consent (adults) or assent (pediatric subjects) to the study

    Unrelated, healthy control inclusion criteria:

    • Age 5 or above
    • Able to communicate well with the investigator, to understand and comply with the requirements of the study
    • Capacity to consent (adults) or assent (pediatric subjects) to the study

    EXCLUSION CRITERIA

    ALS4 exclusion criteria:

    • Patients with known claustrophobia, presence of pacemaker, ferromagnetic material in their body, or any other condition that would preclude MRI assessments

    Related, unaffected healthy control exclusion criteria:

    • Diagnosis of neuromuscular disease or weakness on physical examination
    • Pregnancy

    Unrelated, healthy control exclusion criteria:

    • Diagnosis of neuromuscular disease or weakness on physical examination
    • Patients with known claustrophobia, presence of pacemaker, ferromagnetic material in their body, or any other condition that would preclude MRI assessments

  • Site Contact Information

    National Institutes of Health Clinical Center
    .(JavaScript must be enabled to view this email address) / 800-411-1222 ext TTY8664111010
    Bethesda, Maryland 20892
    United States