A Longitudinal Study of Amyotrophic Lateral Sclerosis (ALS) Biomarkers

• ClinicalTrials.gov Identifier: NCT01495390
• Recruitment Status: Completed
• First Posted: December 20, 2011
• Last Update Posted: May 30, 2017
• Sponsor: Massachusetts General Hospital
• Collaborators: ALS Association; ALS Finding a Cure
• Information provided by (Responsible Party): James D. Berry MD, Massachusetts General Hospital

Study Description

Brief Summary:

The purpose of this study is to collect biofluid samples for the banking and usage in ALS research. 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 develop new therapies.

Condition or disease
Amyotrophic Lateral Sclerosis; Nervous System Diseases; Sclerosis; Motor Neuron Disease; Spinal Cord Diseases; Central Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Diseases; ALS

Detailed Description:

The purpose of the research study is to collect blood samples and cerebrospinal fluid (CSF) from people with amyotrophic lateral sclerosis (ALS). These samples will be collected approximately every 4 months.

Study Design

• Study Type: Observational
• Actual Enrollment: 139 participants
• Observational Model: Case-Only
• Time Perspective: Prospective
• Official Title: A Multicenter Study for the Discovery and Validation of ALS Biomarkers
• Study Start Date: November 2011
• Actual Primary Completion Date: December 31, 2016
• Actual Study Completion Date: December 31, 2016

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. ALS Functional Rating Scale [ Time Frame: Approximately every 4 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.
2. Vital Capacity (VC) [ Time Frame: Approximately every 4 months ]
   The vital capacity (VC) (percent of predicted normal) was determined using the slow VC method. Vital Capacity is the maximum amount of air a person can expel from the lungs after a maximum inhalation. A subject's VC depends on their age, sex and height. The value is recorded as a percent of predicted normal.
3. Hand Held Dynamometry (HHD) [ Time Frame: Approximately every 4 months ]
   Hand Held Dynamometry (HHD) will be used as a quantitative measure of muscle strength for this study. Six proximal muscle groups will be examined bilaterally in both upper and lower extremities (shoulder flexion, elbow flexion, elbow extension, hip flexion, knee flexion, and knee extension), all of which have been validated against maximum voluntary isometric contraction (MVIC) testing.
4. Ashworth Spasticity Scale [ Time Frame: Approximately every 4 months ]
   This is a standard measure for spasticity, has been used in a previous ALS clinical trials, and is applied in the current trial to evaluate the progression of spasticity due to upper motor neuron dysfunction in ALS.
5. Fronto-Temporal Dementia (FTD) Assessment [ Time Frame: Approximately every 4 months ]
   The FTD Screening Assessment is a quickly administered scale used to evaluate memory, executive functions, and language. It is aimed at determining the presence of subtle dysfunction of these domains of cognition and behavior that may portend the onset of FTD or FTD-like symptoms.
6. ALS Cognitive Behavioral Screen (ALS CBS) [ Time Frame: Approximately every 4 months ]

   The ALS Cognitive Behavioral Screen (ALS-CBS™) is a short measure of cognition and behavior in patients with Amyotrophic Lateral Sclerosis (ALS). The cognitive section includes commonly used elements of standard testing batteries, consisting of 8 tasks, with a possible total score of 20. It can be administered by a physician or other clinical care staff and takes approximately 5 minutes to complete.

   The behavioral section (ALS Caregiver Behavioral Questionnaire) is composed of questions sensitive to organic brain changes. It consists of a set of questions that compare changes in personality and behavior since the onset of ALS, as well as yes/no questions about mood, pseudobulbar affect, and fatigue. It is completed by a caregiver, family member or other informant during the same time that the patient completes the cognitive portion. The questionnaire typically takes about 2 minutes to complete.

Biospecimen Retention:   Samples With DNA

Biological samples will be collected from participants with ALS over time. These biological samples include blood (plasma, serum, and RNA) and cerebrospinal fluid (CSF). DNA will be collected at one time point.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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

Inclusion Criteria:

• Age 18 or older
• Diagnosis of suspected, possible, probable or definite ALS according to El Escorial Criteria
• Vital capacity (VC) at least 50 percent predicted
• Able to undergo multiple lumbar punctures

Exclusion Criteria:

• Abnormal CSF pressure or intracranial/intraspinal tumors
• Use of anticoagulant medication that cannot be safely withheld

• Bleeding disorders

  • This is a partial listing.

Contacts and Locations

Locations

United States, Arizona

Barrow Neurological Institute

Phoenix, Arizona, United States, 85013

United States, Florida

Mayo Clinic Jacksonville

Jacksonville, Florida, United States, 32224

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

University of Massachusetts Medical Center

Worcester, Massachusetts, United States, 01655

United States, Pennsylvania

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Massachusetts General Hospital

ALS Association

ALS Finding a Cure

Investigators

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

More Information

Additional Information:

Northeast ALS Consortium Website 

• Responsible Party: James D. Berry MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01495390
• Other Study ID Numbers: BIO-ALS-02
• First Posted: December 20, 2011
• Last Update Posted: May 30, 2017
• Last Verified: May 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Biomarkers; Biological Markers; Surrogate Markers; Clinical Markers; Plasma; Cerebrospinal Fluid; DNA; Serum; RNA

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Diseases; Central Nervous System Diseases; Spinal Cord Diseases; Sclerosis; Pathologic Processes; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases