A Pilot Study of Biomarkers for Spinal Muscular Atrophy - Full Text View

Sponsors and Collaborators:	New England Research Institutes The Spinal Muscular Atrophy Foundation
Information provided by:	New England Research Institutes
ClinicalTrials.gov Identifier:	NCT00756821

Purpose

The goal of this pilot study is to identify a marker or panel of markers in the blood or urine from a wide range of Spinal Muscular Atrophy (SMA) patients that segregates with measures of clinical severity. From this identification of candidate biomarkers, it is hoped that further investigations, both longitudinal natural history and clinical efficacy studies, will verify a biomarker with the sensitivity and specificity that will allow its eventual use as a validated pharmacodynamic marker or surrogate endpoint. In addition, this effort may elucidate biological pathways that may be potential therapeutic targets.

Condition
Spinal Muscular Atrophy

Study Type:	Observational
Study Design:	Cohort, Cross-Sectional
Official Title:	A Pilot Study of Biomarkers for Spinal Muscular Atrophy

Resource links provided by NLM:

Genetics Home Reference related topics: spinal muscular atrophy

MedlinePlus related topics: Spinal Muscular Atrophy Urine and Urination

U.S. FDA Resources

Further study details as provided by New England Research Institutes:

Primary Outcome Measures:

To identify candidate blood and urine biochemical markers that correlate with disease severity as determined by the Modified Hammersmith Functional Motor Scale across a range of type I, type II and type III children with Spinal Muscular Atrophy (SMA) [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine if there are biomarkers from types I-III SMA patients that correlate with SMA type, age at disease onset, 10-meter Timed Walk Test, pulmonary function, nutritional assessment, SMN protein level, SMN transcript level or SMN2 copy number. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
To determine if identified candidate biomarkers are associated with the disease state through comparison of SMA specimens with control volunteer specimens. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

Biospecimen Description:

Whole blood, plasma, PBMCs, and urine

Enrollment:	130
Study Start Date:	October 2008
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Groups/Cohorts
SMA cohort Subjects between the ages of 2-12 years diagnosed with SMA Type I, II, or III.
Control cohort Healthy children between the ages of 2-12 years. These children may be either genetically-related siblings of SMA children (genetically confirmed non-carriers of SMA),or unrelated children.

Detailed Description:

Spinal Muscular Atrophy (SMA) is one of the two most common inherited children's neuromuscular disorders. There currently is no cure and no therapeutics approved to slow progression of the disease. SMA is characterized by a loss of alpha motor neurons in the spinal cord, severe atrophy of proximal muscles and progressive debility and disability due to respiratory, gastrointestinal and functional complications of the disease.

Although SMA is a relatively common orphan disease, recruitment of patients for the number of candidate therapies is expected to become rate-limiting for the development of therapeutics.

STUDY OBJECTIVES

Primary:

To identify candidate blood and urine biochemical markers that correlate with disease severity as determined by the Modified Hammersmith Functional Motor Scale across a range of type I, type II and type III children with Spinal Muscular Atrophy (SMA) (1).

Secondary:

To determine if there are biomarkers from types I-III SMA patients that correlate with SMA type, age at disease onset, 10-meter Timed Walk Test (ambulatory subjects only), pulmonary function, nutritional assessment, SMN protein level, SMN transcript level or SMN2 copy number.
To determine if identified candidate biomarkers are associated with the disease state through comparison of SMA specimens with control volunteer specimens.
To determine if there are potential biochemical pathways that may represent targets for therapeutic intervention in SMA.

Eligibility

Ages Eligible for Study:	2 Years to 12 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

Children's Hospitals Unviersity Hospitals

Criteria

Inclusion Criteria:

Age 2 to 12 years, inclusive
In good health (other than SMA) in the judgement of the clinical investigator ar the time of assessment

Exclusion Criteria:

Systemic or specific-organ illness
Any known genetic condition other than SMA requiring pharmaceutical treatment
Use of any putative SMN-enhancing medications or treatments in the past 14 days prior to enrollment
Use of carnitine, creatine, oral albuterol or riluzole for 14 days prior to enrollment
Use of any oral prescription medications for 14 days prior to enrollment (exceptions: anti-reflux medications, constipation or stoll softening medications, stool bulking agents, and inhaled bronchodilator medications)
Any illness requiring treatment of antibiotics or anti-inflammatory medication within the past 14 days
Any rash requiring treatment within the past 7 days
Any severe asthma attack requiring treatment with oral or parenteral steroids within the past 7 days
Any fever over 100 degrees Fahrenheit or 38 degree Celsius within the past 7 days
Any immunization within the past 7 days
Any injury sustained that resulted in a bone fracture or needed stitches within the past 7 days
Any surgery within the past 7 days
Any receipt of anesthesia within the past 7 days
Any Emergency Room visit or hospitalization within the past 7 days
Any stomach illness with vomiting within the past 7 days
Any migraine headache within the past 7 days
Participation in a clinical trial (except observational studies) within the past 7 days

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00756821

Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Stanford, California, United States, 94305
United States, Colorado
The Children's Hospital
Aurora, Colorado, United States, 80045
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Michigan
Children's Hospital of Michigan, Detroit
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University Medical School
St. Louis, Missouri, United States, 63110
United States, New York
Columbia University SMA Clinical Research Center
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
The Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Children's Medical Center - Dallas
Dallas, Texas, United States, 75207
United States, Utah
University of Utah
Salt lake City, Utah, United States, 84132
United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Canada, Ontario
The Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Children's Hospital - London Health Sciences Center
London, Ontario, Canada, N6A 2E3

Sponsors and Collaborators

New England Research Institutes

The Spinal Muscular Atrophy Foundation

Investigators

Principal Investigator:	Richard Finkel, MD	Children's Hospital of Philadelphia
Principal Investigator:	Thomas Crawford, MD	Johns Hopkins University
Principal Investigator:	Petra Kaufmann, MD	Columbia University

More Information

Additional Information:

The mission of the Spinal Muscular Atrophy Foundation is to accelerate the development of a treatment for SMA, the number one genetic killer of infants and toddlers. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	The Spinal Muscular Atrophy Foundation ( The Spinal Muscular Atrophy Foundation )
Study ID Numbers:	BforSMA
Study First Received:	September 18, 2008
Last Updated:	March 30, 2009
ClinicalTrials.gov Identifier:	NCT00756821 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by New England Research Institutes:

Spinal Muscular Atrophy
Blood Biomarkers
Urine Biomarkers
Type I Spinal Muscular Atrophy
Type II Spinal Muscular Atrophy

Type III Spinal Muscular Atrophy
Modified Hammersmith Functional Motor Scale
Disease severity
Biomarkers

Study placed in the following topic categories:

Pathological Conditions, Anatomical
Spinal Cord Diseases
Spinal Muscular Atrophy
Central Nervous System Diseases
Neurodegenerative Diseases
Signs and Symptoms
Werdnig-Hoffmann Disease
Neuromuscular Diseases

Muscular Atrophy, Spinal
Neurologic Manifestations
Atrophy
Degenerative Motor System Disease
Motor Neuron Disease
Muscular Atrophy
Progressive Spinal Muscular Atrophy

Additional relevant MeSH terms:

Pathological Conditions, Anatomical
Neuromuscular Manifestations
Spinal Cord Diseases
Nervous System Diseases
Central Nervous System Diseases
Neurodegenerative Diseases
Signs and Symptoms

Neuromuscular Diseases
Muscular Atrophy, Spinal
Neurologic Manifestations
Atrophy
Motor Neuron Disease
Muscular Atrophy

ClinicalTrials.gov processed this record on September 10, 2009