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

Study Description

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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.

Condition or disease	Intervention/treatment
Amyotrophic Lateral Sclerosis; Lou Gehrig's Disease; Primary Lateral Sclerosis; Nervous System Diseases; Hereditary Spastic Paraparesis	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 Design

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Study Type :	Observational
Actual Enrollment :	475 participants
Observational Model:	Case Control
Time Perspective:	Prospective
Official Title:	A Multicenter Study for the Validation of ALS Biomarkers
Study Start Date :	April 2008
Actual Primary Completion Date :	November 2015
Actual Study Completion Date :	November 2015

Groups and Cohorts

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

Outcome Measures

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Primary Outcome Measures :

1. ALS Functional Rating Scale (ALSFRS-R) [ Time Frame: 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.

Biospecimen Retention:   Samples With DNA

650 blood samples (plasma and serum)will be collected from four groups: ALS volunteers diagnosed with ALS, volunteers with pure lower or pure upper motor neuron diseases, volunteers with other neurological diseases and healthy control volunteers.

300 cerebrospinal fluid (CSF) samples will be collected from all four groups: ALS volunteers diagnosed with ALS, volunteers with pure lower or pure upper motor neuron diseases, volunteers with other neurological diseases and healthy control volunteers.

Up to 600 DNA samples will also be collected from all 4 groups: ALS volunteers diagnosed with ALS, volunteers with pure lower or pure upper motor neuron diseases, volunteers with other neurological diseases and healthy control volunteers.

Eligibility Criteria

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Ages Eligible for Study:	30 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
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.

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).

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 30 Study Locations

Sponsors and Collaborators

Massachusetts General Hospital

ALS Association

ALS Therapy Alliance

National Institutes of Health (NIH)

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:	James D. Berry, MD, MPH	Massachusetts General Hospital

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

ALS Association Website 

NEALS ALS Consortium 

Responsible Party:	James D. Berry MD, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00677768 History of Changes
Other Study ID Numbers:	BIO_ALS-01; 5RC1NS068179-02 ( U.S. NIH Grant/Contract )
First Posted:	May 14, 2008
Last Update Posted:	June 3, 2016
Last Verified:	June 2016

Keywords provided by James D. Berry MD, Massachusetts General Hospital:

Biomarkers; Plasma; Cerebrospinal Fluid; DNA; Serum

Additional relevant MeSH terms:

Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Nervous System Diseases; Paraparesis; Paraparesis, Spastic; Pathologic Processes; Neurodegenerative Diseases; Neuromuscular Diseases	Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Paresis; Neurologic Manifestations; Signs and Symptoms