A Pilot Study of Biomarkers for Spinal Muscular Atrophy

Spinal Muscular Atrophy Clinical Trial

— BforSMA  

Official title:

A Pilot Study of Biomarkers for Spinal Muscular Atrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00756821
• Other study ID #: BforSMA
• Status: Completed
• Phase: N/A
• First received: September 18, 2008
• Last updated: October 23, 2012
• Start date: October 2008
• Est. completion date: March 2009

Study information

• Verified date: October 2012
• Source: New England Research Institutes
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 2 Years to 12 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Atrophy
• Muscular Atrophy
• Muscular Atrophy, Spinal
• Spinal Muscular Atrophy

Locations

Country	Name	City	State
Canada	Children's Hospital - London Health Sciences Center	London	Ontario
Canada	The Hospital for Sick Children	Toronto	Ontario
United States	The Children's Hospital	Aurora	Colorado
United States	Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Children's Medical Center - Dallas	Dallas	Texas
United States	Children's Hospital of Michigan, Detroit	Detroit	Michigan
United States	University of Iowa	Iowa City	Iowa
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	Columbia University SMA Clinical Research Center	New York	New York
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Utah	Salt lake City	Utah
United States	Washington University Medical School	St. Louis	Missouri
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
New England Research Institutes	The Spinal Muscular Atrophy Foundation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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 year	No
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, pulmonary function, nutritional assessment, SMN protein level, SMN transcript level or SMN2 copy number.		1 year	No
Secondary	To determine if identified candidate biomarkers are associated with the disease state through comparison of SMA specimens with control volunteer specimens.		1 year	No

External 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.