A Pilot Study of Biomarkers for Spinal Muscular Atrophy

NCT ID: NCT00756821

Last Updated: 2012-10-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

130 participants

Study Classification

OBSERVATIONAL

Study Start Date

2008-10-31

Study Completion Date

2009-03-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Spinal Muscular Atrophy

Keywords

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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 Design

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Observational Model Type

COHORT

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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SMA cohort

Subjects between the ages of 2-12 years diagnosed with SMA Type I, II, or III.

No interventions assigned to this group

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.

No interventions assigned to this group

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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The Spinal Muscular Atrophy Foundation

OTHER

Sponsor Role collaborator

Carelon Research

OTHER

Sponsor Role lead

Responsible Party

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The Spinal Muscular Atrophy Foundation

Principal Investigators

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Richard Finkel, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Thomas Crawford, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Petra Kaufmann, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Stanford University

Stanford, California, United States

Site Status

The Children's Hospital

Aurora, Colorado, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Children's Hospital Boston

Boston, Massachusetts, United States

Site Status

Children's Hospital of Michigan, Detroit

Detroit, Michigan, United States

Site Status

Mayo Clinic Rochester

Rochester, Minnesota, United States

Site Status

Washington University Medical School

St Louis, Missouri, United States

Site Status

Columbia University SMA Clinical Research Center

New York, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Medical Center - Dallas

Dallas, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, United States

Site Status

Children's Hospital - London Health Sciences Center

London, Ontario, Canada

Site Status

The Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Finkel RS, Crawford TO, Swoboda KJ, Kaufmann P, Juhasz P, Li X, Guo Y, Li RH, Trachtenberg F, Forrest SJ, Kobayashi DT, Chen KS, Joyce CL, Plasterer T; Pilot Study of Biomarkers for Spinal Muscular Atrophy Trial Group. Candidate proteins, metabolites and transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) clinical study. PLoS One. 2012;7(4):e35462. doi: 10.1371/journal.pone.0035462. Epub 2012 Apr 27.

Reference Type DERIVED
PMID: 22558154 (View on PubMed)

Crawford TO, Paushkin SV, Kobayashi DT, Forrest SJ, Joyce CL, Finkel RS, Kaufmann P, Swoboda KJ, Tiziano D, Lomastro R, Li RH, Trachtenberg FL, Plasterer T, Chen KS; Pilot Study of Biomarkers for Spinal Muscular Atrophy Trial Group. Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study. PLoS One. 2012;7(4):e33572. doi: 10.1371/journal.pone.0033572. Epub 2012 Apr 27.

Reference Type DERIVED
PMID: 22558076 (View on PubMed)

Related Links

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http://www.smafoundation.org

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.

Other Identifiers

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BforSMA

Identifier Type: -

Identifier Source: org_study_id