Clinical trial NCT00677768: Validation of Biomarkers in Amyotrophic Lateral Sclerosis (ALS)
Official title: A Multicenter Study for the Validation of ALS Biomarkers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Amyotrophic Lateral Sclerosis
Lou Gehrig's Disease
Primary Lateral Sclerosis
Nervous System Diseases
Hereditary Spastic Paraparesis
Keywords: Biomarkers
Plasma
Cerebrospinal Fluid
DNA
Serum
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: ALS Association
name: ALS Therapy Alliance
name: National Institutes of Health (NIH)
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2008-05-14
Enrollment: 475
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: ALS Functional Rating Scale (ALSFRS-R)
timeFrame: Every 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates, Ltd.
state: Arizona
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Neurology
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Grand Rapids
country: United States
facility: Saint Mary's Healthcare
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New Brunswick
country: United States
facility: Robert Wood Johnson/UMDNJ
state: New Jersey
city: Albany
country: United States
facility: Upstate Clinical Research, LLC
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center, PACC
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Carolinas Health Care
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Columbus
country: United States
facility: OSU Medical Center
state: Ohio
city: Portland
country: United States
facility: Providence ALS Clinic
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Methodist Neurological Institute
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Montreal
country: Canada
facility: Montreal Neurological Institute
state: Quebec
Study officials:
affiliation: Massachusetts General Hospital
name: James D. Berry, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: