Clinical trial NCT00756821: A Pilot Study of Biomarkers for Spinal Muscular Atrophy
Official title: A Pilot Study of Biomarkers for Spinal Muscular Atrophy
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Carelon Research
Sponsor class: OTHER
Collaborators: name: The Spinal Muscular Atrophy Foundation
First posted: 2008-09-22
Enrollment: 130
Sex: ALL
Minimum age (years): 2
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Children's Hospitals Unviersity Hospitals

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.

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 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

Primary outcomes:
measure: 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)
timeFrame: 1 year
Secondary outcomes:
measure: 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.
timeFrame: 1 year
measure: To determine if identified candidate biomarkers are associated with the disease state through comparison of SMA specimens with control volunteer specimens.
timeFrame: 1 year
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: The Children's Hospital
state: Colorado
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan, Detroit
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: St. Louis
country: United States
facility: Washington University Medical School
state: Missouri
city: New York
country: United States
facility: Columbia University SMA Clinical Research Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: Children's Medical Center - Dallas
state: Texas
city: Salt lake City
country: United States
facility: University of Utah
state: Utah
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: London
country: Canada
facility: Children's Hospital - London Health Sciences Center
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Richard Finkel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins University
name: Thomas Crawford, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University
name: Petra Kaufmann, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.