Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS) (BIO_ALS-01)

A Multicenter Study for the Validation of ALS Biomarkers

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.

Study Overview

• Status: Completed
• Conditions: Nervous System Diseases; Amyotrophic Lateral Sclerosis; Primary Lateral Sclerosis; Lou Gehrig's Disease; Hereditary Spastic Paraparesis
• Intervention / Treatment: Other: No intervention

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.

• Study Type: Observational
• Enrollment (Actual): 475

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Neurological Associates, Ltd.
  • California
    • Orange, California, United States, 92868
      • University of California Irvine
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Neurology
    • Miami, Florida, United States, 33136
      • University of Miami
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02129
      • Massachusetts General Hospital
    • Burlington, Massachusetts, United States, 01805
      • Lahey Clinic
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Saint Mary's Healthcare
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis University
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Robert Wood Johnson/UMDNJ
  • New York
    • Albany, New York, United States, 12205
      • Upstate Clinical Research, LLC
    • New York, New York, United States, 10003
      • Beth Israel Medical Center, PACC
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Health Care
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • OSU Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence ALS Clinic
    • Portland, Oregon, United States, 97233
      • Oregon Health & Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State University
    • Philadelphia, Pennsylvania, United States, 19107
      • Drexel University College of Medicine
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • Methodist Neurological Institute
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Volunteers will be invited to participate in this study by their neurologists either in clinic or at a regular scheduled appointment visit.

Description

1. ALS Volunteers

   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)

2. 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)

3. 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)

4. 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 Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy Controls	Other: No intervention; Sample collection
Early ALS	Other: No intervention; Sample collection
Suspected ALS	Other: No intervention; Sample collection
Disease Mimics of ALS	Other: No intervention; Sample collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ALS Functional Rating Scale (ALSFRS-R)	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.	Every 6 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); National Institutes of Health (NIH); ALS Association; ALS Therapy Alliance
• Investigators: Principal Investigator: James D. Berry, MD, MPH, Massachusetts General Hospital

Publications and helpful links

Helpful Links

• ALS Association Website
• NEALS ALS Consortium

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: May 9, 2008
• First Submitted That Met QC Criteria: May 13, 2008
• First Posted (Estimate): May 14, 2008

Study Record Updates

• Last Update Posted (Estimate): June 3, 2016
• Last Update Submitted That Met QC Criteria: June 2, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: DNA; Serum; Biomarkers; Plasma; Cerebrospinal Fluid
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Paresis; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Nervous System Diseases; Paraparesis; Paraparesis, Spastic
• Other Study ID Numbers: BIO_ALS-01; 5RC1NS068179-02 (U.S. NIH Grant/Contract)