A Pilot Study of Biomarkers for Spinal Muscular Atrophy

NCT00756821 | Completed

• 1 other identifier: BforSMA
• Study Type: observational
• Target: 130
• Locations: 2 countries
• Sites: 18

Brief Summary

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.

Conditions

Spinal Muscular Atrophy

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 year

Secondary Outcomes (2)

• 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.

  1 year

• To determine if identified candidate biomarkers are associated with the disease state through comparison of SMA specimens with control volunteer specimens.

  1 year

Study Arms (2)

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.

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Children's Hospitals Unviersity Hospitals

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Carelon Research: lead
• The Spinal Muscular Atrophy Foundation: collaborator

Study Sites (18)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

The Children's Hospital

Aurora, Colorado, 80045, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Michigan, Detroit

Detroit, Michigan, 48201, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University Medical School

St Louis, Missouri, 63110, United States

Location

Columbia University SMA Clinical Research Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Medical Center - Dallas

Dallas, Texas, 75207, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Children's Hospital - London Health Sciences Center

London, Ontario, N6A 2E3, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (2)

• 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.

  PMID: 22558154 DERIVED

• 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.

  PMID: 22558076 DERIVED

Related Links

• 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.

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, plasma, PBMCs, and urine

MeSH Terms

Conditions

Muscular Atrophy, Spinal; Spinal Muscular Atrophies of Childhood

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases; Heredodegenerative Disorders, Nervous System; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Richard Finkel, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• Thomas Crawford, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Petra Kaufmann, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 18, 2008
• First Posted: September 22, 2008
• Study Start: October 1, 2008
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: October 24, 2012

Record last verified: 2012-10

Locations

CA (2); US (16)