MedPath

Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)

Completed
Conditions
Nervous System Diseases
Amyotrophic Lateral Sclerosis
Lou Gehrig's Disease
Primary Lateral Sclerosis
Hereditary Spastic Paraparesis
Interventions
Other: No intervention
Registration Number
NCT00677768
Lead Sponsor
Massachusetts General Hospital
Brief Summary

The purpose of this study is to collect 650 blood and 300 cerebrospinal fluid (CSF) samples from people with amyotrophic lateral sclerosis (ALS), pure lower or upper motor neuron diseases, as well as other neurodegenerative diseases and from people with no neurological disorder. Through comparison of these samples, the researchers hope to learn more about the underlying cause of ALS, as well as find unique biological markers, which could be used to diagnose ALS and monitor disease progression.

Additionally, up to 600 blood samples will be collected for a sub-study for DNA analysis. Studying components of the blood, such as DNA, may help us understand what happens when genes function abnormally and how it might be related to disease.

Detailed Description

Researchers tested what changes happen in volunteers with ALS that can be seen in the blood and what changes are unique to ALS and are different from those found in healthy volunteers and volunteers with neurological diseases other than ALS. These changes are called biomarkers. Biomarkers for ALS have been found in blood collected in earlier phases of this study. Biomarkers are non-genetic elements in your blood that may help to make diagnosing ALS easier. In the next phase, comparison of these changes in the blood of volunteers with ALS and without ALS will be used to confirm these biomarkers and to develop a tool to diagnose and monitor progression of ALS.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
475
Inclusion Criteria
  • Diagnosis of possible (excluding volunteers with UMN signs ONLY), probable, probable-laboratory supported, or definite ALS, either sporadic or familial according to revised El Escorial criteria
    • Disease duration of less than or equal to two years from symptom onset
    • Age 30-80 years at the time of disease onset
    • Ability to provide informed consent
    • Ability to comply with study procedures
    • Medically safe to have lumbar puncture (lumbar puncture volunteers only)
Exclusion Criteria
  • Clinical evidence of chronic liver or renal failure
    • Presence of a bleeding disorder, problems with CSF pressure, allergy to local anesthetics, or a topical or other skin infection at the LP site (lumbar puncture volunteers only)
    • Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin (lumbar puncture volunteers only)
  1. Suspected ALS (PMND) Volunteers

    Inclusion Criteria:

    • Diagnosis of suspected ALS defined as presence of UMN or LMN signs alone and the diagnosis of Clinically Probably Laboratory-Supported ALS CANNOT be proven by evidence in clinical grounds in conjunction with electrodiagnostic, neurophysiologic, neuroimaging or clinically laboratory studies
    • Disease duration of less than or equal to four years from symptom onset
    • Age 30-80 years at time of disease onset
    • Ability to provide informed consent
    • Ability to comply with study procedures
    • Medically safe to have lumbar puncture (lumbar puncture volunteers only)

    Exclusion Criteria:

    • Clinical evidence of chronic liver or renal failure
    • Genetically confirmed diagnosis of hereditary spastic paraparesis or spinal motor atrophy (SMA) disease
    • Presence of a bleeding disorder, problems with CSF pressure, allergy to local anesthetics, or a topical or other skin infection at the LP site (lumbar puncture volunteers only)
    • Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin (lumbar puncture volunteers only)
  2. Neurological Disease Mimic Volunteers

    Inclusion Criteria:

    Diagnosis of one of the following:

    Pure Lower Motor Neuron Disease (LMND) mimics:

    • Multi-focal motor neuropathy
    • Autoimmune motor neuropathy
    • Cervical or lumbosacral radiculopathies

    Peripheral mononeuropathies:

    • Ulnar neuropathy
    • Carpal tunnel syndrome/median neuropathy
    • Peroneal neuropathy
    • Sciatic neuropathy
    • Spinal muscular atrophy
    • Spinobulbar muscular atrophy (Kennedy's disease)
    • Charcot Marie-Tooth Disease (CMT)

    Pure Upper Motor Neuron Disease (UMND) mimics:

    • Cervical myelopathy
    • Multiple sclerosis
    • Hereditary spastic paraparesis
    • Age 30-80 years
    • Ability to provide informed consent
    • Ability to comply with study procedures
    • Medically safe to have lumbar puncture (lumbar puncture volunteers only)

    Exclusion Criteria:

    • Diagnosis of suspected, possible, probable or definite ALS either sporadic or familial
    • Presence of positive family history of ALS
    • Clinical evidence of chronic renal or liver failure
    • Presence of a bleeding disorder, problems with CSF pressure, allergy to local anesthetics, or a topical or other skin infection at the LP site (lumbar puncture volunteers only)
    • Use of any anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin (lumbar puncture volunteers only)
  3. Healthy Control Volunteers Inclusion Criteria

    • Absence of a known neurological disorder.
    • Age 30 - 80 years.
    • Ability to provide informed consent.
    • Ability to comply with study procedures.
    • Medically safe to have lumbar puncture.

Exclusion Criteria:

  • History of ALS, myopathy, neuropathy, ALS mimic disorder or other neurodegenerative disease.
  • Presence of positive family history of ALS.
  • Clinical evidence of chronic liver or renal failure.
  • Presence of bleeding disorder, problems with CSF pressure, allergy to local anesthetics, or a topical or other skin infection at the LP site (LP research volunteers only).
  • Research participant must not be taking anti-platelet or anticoagulant drugs, such as plavix, aggrenox, ticlid, warfarin or coumadin (LP research volunteers only).

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Suspected ALSNo intervention-
Healthy ControlsNo intervention-
Disease Mimics of ALSNo intervention-
Early ALSNo intervention-
Primary Outcome Measures
NameTimeMethod
ALS Functional Rating Scale (ALSFRS-R)Every 6 months

The ALSFRS-R is a quickly administered (5 min) ordinal rating scale used to determine a subject's assessment of their capability and independence in 12 functional activities. There are 12 questions, graded by the subject 0-4 (4 is normal). Score of 0 (worst) to 48 (best). Reflects speech and swallowing, fine motor skills, large motor skills, and breathing.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (30)

Emory University

🇺🇸

Atlanta, Georgia, United States

University of Chicago

🇺🇸

Chicago, Illinois, United States

University of California Irvine

🇺🇸

Orange, California, United States

Mayo Clinic Neurology

🇺🇸

Jacksonville, Florida, United States

Johns Hopkins University

🇺🇸

Baltimore, Maryland, United States

Lahey Clinic

🇺🇸

Burlington, Massachusetts, United States

Dartmouth Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Saint Mary's Healthcare

🇺🇸

Grand Rapids, Michigan, United States

Saint Louis University

🇺🇸

Saint Louis, Missouri, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Beth Israel Medical Center, PACC

🇺🇸

New York, New York, United States

Carolinas Health Care

🇺🇸

Charlotte, North Carolina, United States

Robert Wood Johnson/UMDNJ

🇺🇸

New Brunswick, New Jersey, United States

Upstate Clinical Research, LLC

🇺🇸

Albany, New York, United States

SUNY Upstate Medical University

🇺🇸

Syracuse, New York, United States

OSU Medical Center

🇺🇸

Columbus, Ohio, United States

Wake Forest University

🇺🇸

Winston-Salem, North Carolina, United States

Pennsylvania State University

🇺🇸

Hershey, Pennsylvania, United States

Drexel University College of Medicine

🇺🇸

Philadelphia, Pennsylvania, United States

University of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Montreal Neurological Institute

🇨🇦

Montreal, Quebec, Canada

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

University of Miami

🇺🇸

Miami, Florida, United States

Phoenix Neurological Associates, Ltd.

🇺🇸

Phoenix, Arizona, United States

Hennepin County Medical Center

🇺🇸

Minneapolis, Minnesota, United States

Duke University Medical Center

🇺🇸

Durham, North Carolina, United States

Providence ALS Clinic

🇺🇸

Portland, Oregon, United States

Oregon Health & Science University

🇺🇸

Portland, Oregon, United States

Methodist Neurological Institute

🇺🇸

Houston, Texas, United States

University of Utah

🇺🇸

Salt Lake City, Utah, United States

© Copyright 2025. All Rights Reserved by MedPath