Spinal Muscular AtrophyBforSMANCT00756821
A Pilot Study of Biomarkers for Spinal Muscular Atrophy
An observational study of Spinal Muscular Atrophy, run by Carelon Research at 18 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 2 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Spinal Muscular Atrophy
- How many people
- 130 participants
- Where
- 18 sitesin 2 countries
- Study dates
- Oct 2008to Mar 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 12 years
- All sexes
- Healthy volunteers accepted
- Child
Study population: Children's Hospitals Unviersity Hospitals
Who may be able to join
- Age 2 to 12 years, inclusive
- In good health (other than SMA) in the judgement of the clinical investigator ar the time of assessment
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
18 sites in 2 countries.
18 sites in 2 countries
United States16 sites
The Children's Hospital
Aurora, Colorado, 80045
Johns Hopkins Hospital
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Children's Hospital Boston
Boston, Massachusetts, 02115
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
The Ohio State University
Columbus, Ohio, 43210
Children's Medical Center - Dallas
Dallas, Texas, 75207
Children's Hospital of Michigan, Detroit
Detroit, Michigan, 48201
University of Iowa
Iowa City, Iowa, 52242
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Columbia University SMA Clinical Research Center
New York, New York, 10032
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Mayo Clinic Rochester
Rochester, Minnesota, 55905
University of Utah
Salt Lake City, Utah, 84132
Washington University Medical School
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
Canada2 sites
Children's Hospital - London Health Sciences Center
London, Ontario, N6A 2E3
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
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.
Read the 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.
- 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
- Medical subject headings
- Muscular Atrophy, Spinal, Spinal Muscular Atrophies of Childhood
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 1 year
To determine if identified candidate biomarkers are associated with the disease state through comparison of SMA specimens with control volunteer specimens.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2008 (estimated)
- Study startOct 2008
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Collaborators
- The Spinal Muscular Atrophy Foundation
- Investigators
- Richard Finkel, MD, Principal investigator, Children's Hospital of PhiladelphiaThomas Crawford, MD, Principal investigator, Johns Hopkins UniversityPetra Kaufmann, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00756821
- Sponsor's protocol ID
- BforSMA
- Acronym
- BforSMA
- Status last verified
- Oct 2012
- First submitted
- 18 Sep 2008
- Last updated
- 24 Oct 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 22558154Crawford 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.
PubMed 22558076
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Biomarkers for Spinal Muscular Atrophy
- ClinicalTrials.gov ID
- NCT00756821
- Acronym / sponsor ID
- BforSMA / BforSMA
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Collaborators
- The Spinal Muscular Atrophy Foundation
- Study start
- Oct 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 22 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 2 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
- Study population
- Children's Hospitals Unviersity Hospitals
Key inclusion criteria (2 listed)
- Age 2 to 12 years, inclusive
- In good health (other than SMA) in the judgement of the clinical investigator ar the time of assessment
Key exclusion criteria (17 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
2 secondary outcomes
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2012.
- Derived from this study: PubMed 22558154Finkel 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.
- Derived from this study: PubMed 22558076Crawford 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.
- 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.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Finkel, MD principal investigator
Children's Hospital of Philadelphia
Thomas Crawford, MD principal investigator
Johns Hopkins University
Petra Kaufmann, MD principal investigator
Columbia University
18 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spinal Muscular Atrophy, run by Carelon Research at 18 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Oct 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00756821, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2012.