Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4 and Other Inherited Neurological Disorders of RNA Processing
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|ClinicalTrials.gov Identifier: NCT04394871|
Recruitment Status : Recruiting
First Posted : May 20, 2020
Last Update Posted : June 2, 2020
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).
To learn how the binding of RNA with DNA (R-loops) is related to neurological disease.
People age 5 and older with ALS4, PEOB2, AGS, and AOA2. Healthy relatives and nonrelatives are also needed.
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:
Tests of muscle strength and volume and physical function
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.
|Condition or disease|
|Amyotrophic Lateral Sclerosis Type 4 Inherited Neurological Disorders of RNA Processing|
|Study Type :||Observational|
|Estimated Enrollment :||315 participants|
|Official Title:||An Observational Study to Assess Clinical Manifestations and Biomarkers in Amyotrophic Lateral Sclerosis Type 4 and Other Inherited Neurological Disorders of RNA Processing|
|Estimated Study Start Date :||June 5, 2020|
|Estimated Primary Completion Date :||September 30, 2025|
|Estimated Study Completion Date :||December 31, 2025|
Patients with ALS4 inherited defect in the senataxin (SETX) gene.
Disease Control Participants
Disease control participants with mutation in other genes which alter RNA processing (e.g., RNASEH1+2 and loss of function SETX mutations in patients with ataxia and oculomotor apraxia type 2[AOA2]).
Related, Unaffected Healthy Controls
Unrelated, unaffected healthy relatives of the ALS4 and disease control groups enrolled as controls.
Unrelated, Healthy Controls
Unrelated, healthy volunteers who are age and sex matched to the affected ALS4 and disease control participants.
- Disease progression as measured by thigh muscle volume and other study measures [ Time Frame: Baseline and annually at visits 2 - 4 ]Clinical and molecular measurements in ALS4 patients and other inherited neurological disorders of RNA processing will be assessed over the course of the study.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04394871
|Contact: Angela Kokkinis, R.N.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Christopher Grunseich, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|