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Protocol Details

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

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

20-N-0064

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 5
Max Age: N/A

Referral Letter Required

No

Population Exclusion(s)

None

Special Instructions

Currently Not Provided

Keywords

Natural History Study;
Biomarker Development

Recruitment Keyword(s)

None

Condition(s)

Amyotrophic Lateral Sclerosis Type 4;
Inherited Neurological Disorders of RNA Processing

Investigational Drug(s)

None

Investigational Device(s)

None

Intervention(s)

None

Supporting Site

National Institute of Neurological Disorders and Stroke

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.

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Eligibility

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

-Pregnancy

-Disease control exclusion criteria:

--Pregnancy

-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

-Pregnancy


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Citations:

Rabin BA, Griffin JW, Crain BJ, Scavina M, Chance PF, Cornblath DR. Autosomal dominant juvenile amyotrophic lateral sclerosis. Brain. 1999 Aug;122 ( Pt 8):1539-50.

Grunseich C, Wang IX, Watts JA, Burdick JT, Guber RD, Zhu Z, Bruzel A, Lanman T, Chen K, Schindler AB, Edwards N, Ray-Chaudhury A, Yao J, Lehky T, Piszczek G, Crain B, Fischbeck KH, Cheung VG. Senataxin Mutation Reveals How R-Loops Promote Transcription by Blocking DNA Methylation at Gene Promoters. Mol Cell. 2018 Feb 1;69(3):426-437.e7. doi: 10.1016/j.molcel.2017.12.030. Epub 2018 Jan 27.

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Contacts:

Principal Investigator

Referral Contact

For more information:

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



Angela Kokkinis, R.N.
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health
Building 10
Room 5S-219
10 Center Drive
Bethesda, Maryland 20892
(301) 451-8146
akokkinis@mail.cc.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT04394871

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