A Pilot Study of Biomarkers for Spinal Muscular Atrophy (BforSMA)

October 23, 2012 updated by: HealthCore-NERI

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.

Study Overview

Status

Completed

Conditions

Spinal Muscular Atrophy

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.

Study Type

Observational

Enrollment (Actual)

130

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 8 years (Child)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Children's Hospitals Unviersity Hospitals

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Observational Models: Cohort
Time Perspectives: Cross-Sectional

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
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	1 year
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	1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

HealthCore-NERI

Collaborators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2008

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)