Status:

RECRUITING

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

Lead Sponsor:

National Institute of Neurological Disorders and Stroke (NINDS)

Conditions:

Amyotrophic Lateral Sclerosis Type 4

Inherited Neurological Disorders of RNA Processing

Eligibility:

All Genders

5-120 years

Brief Summary

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 ...

Detailed Description

Objective: Amyotrophic lateral sclerosis type 4 (ALS4) is an inherited form of motor neuron disease caused by a gain of function mutation in the senataxin (SETX) gene. The main goal of this study wil...

Eligibility Criteria

Inclusion

  • INCLUSION CRITERIA:
  • ALS4 RNA metabolism 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
  • Gain of function inclusion criteria:
  • Age 5 or above
  • Genetic diagnosis of mutation resulting in a gain of function mechanism (for example, heterozygous mutations in SETX or heterozygous mutations in KCC3)
  • Able to communicate well with the investigator, to understand and comply with the requirements of the studyCapacity to consent (adults) or assent (pediatric subjects) to the study
  • Capacity to consent (adults) or assent (pediatric subjects) to the study
  • EXCLUSION CRITERIA:
  • ALS4 RNA metabolism exclusion criteria:
  • Patients with known claustrophobia, presence of pacemaker, ferromagnetic material in their body, or any other condition that would preclude MRI assessments
  • Pregnancy
  • Note: An Adult RNA metabolism ALS4 Patient who meets any of the following criteria will be excluded from the lumbar puncture procedure:
  • PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
  • INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
  • History of a bleeding disorder
  • Use of anticoagulants
  • Disease control exclusion criteria:
  • -Pregnancy
  • Related, unaffected healthy control exclusion criteria:
  • Diagnosis of neuromuscular disease or weakness on physical examination
  • Pregnancy
  • Note: An Adult Related, Unaffected Healthy Control who meets any of the following criteria will be excluded from the lumbar puncture procedure:
  • PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
  • INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
  • History of a bleeding disorder
  • Use of anticoagulants
  • 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
  • Note: An Adult Unrelated, Healthy Control who meets any of the following criteria will be excluded from the lumbar puncture procedure:
  • PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
  • INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
  • History of a bleeding disorder
  • Use of anticoagulants
  • Gain of function exclusion criteria:
  • Pregnancy
  • Note: An Adult Gain of Function patient who meets any of the following criteria will be excluded from the lumbar puncture procedure:
  • PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
  • INR greater than or equal to 1.5, thrombocytopenia (\<70,000), or abnormal bleeding time or platelet dysfunction
  • History of a bleeding disorder
  • Use of anticoagulants

Exclusion

    Key Trial Info

    Start Date :

    December 14 2020

    Trial Type :

    OBSERVATIONAL

    Allocation :

    ESTIMATED

    End Date :

    December 31 2030

    Estimated Enrollment :

    330 Patients enrolled

    Trial Details

    Trial ID

    NCT04394871

    Start Date

    December 14 2020

    End Date

    December 31 2030

    Last Update

    November 28 2025

    Active Locations (1)

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    National Institutes of Health Clinical Center

    Bethesda, Maryland, United States, 20892