Spinal Muscular AtrophyBADGESNCT02550691
Identification of a Biomarker Associated With Cis-duplication of the SMN1 Gene
A study testing blood sampling in people with Spinal Muscular Atrophy, run by University Hospital, Rouen at 2 sites in France.
Trial summary
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder characterized by loss of motor neurons in the anterior horn of the spinal cord and leading to muscle atrophy. SMA has an autosomal recessive inheritance and affects 1 in 6000 infants with a carrier frequency of 1 in 40. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Spinal Muscular Atrophy
- What is being tested?
- blood sampling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 2 sitesFrance
- Study dates
- 15 Dec 2015to 4 Jul 2016
- Phase
- Interventional
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adult individual
- Individual with either 2 copies of the SMN1 gene (control-1 group), 3 copies of the SMN1 gene (test group), or 3 copies of the SMN2 gene (control-2 group).
- Individual with a social insurance
- Signed consent form
Who cannot join
- Pregnant women, nursing women
- Individual without freedom by administrative decision or judicial decision or individual under administrative supervision or legal guardianship
Trial locations and contacts
2 sites in 1 country.
France2 sites
Nantes University Hospital
Nantes
Rouen University Hospital
Rouen, 76031
About this study
Official title: Identification of a Biomarker Associated With Cis-duplication of the SMN1 Gene Aiming at Improving the Genetic Counseling in Spinal Muscular Atrophy Families
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder characterized by loss of motor neurons in the anterior horn of the spinal cord and leading to muscle atrophy. SMA has an autosomal recessive inheritance and affects 1 in 6000 infants with a carrier frequency of 1 in 40. In most cases, it is caused by homozygous gene deletion or gene conversion of the SMN1 gene (0+0 genotype) on 5q11-q13. This genomic region has been duplicated and inverted during evolution. Thus the SMN1 gene has a very homologous copy, called SMN2. Genetic counseling aim at detecting carriers with only one copy of the SMN1 gene (0+1 genotype). SMA carrier testing relies on total copy number quantification of the SMN1 copies by quantitative PCR methods. Nevertheless, cis-duplication of the SMN1 gene on one allele and deletion on the second allele (2+0 genotype) can lead to a misinterpretation as molecular methods show 2 copies of the SMN1 gene and cannot detect the carrier status.
The aim of the study is the characterization of a biomarker specific of the cis-duplication of the SMN1 gene in order to allow the detection of this 2+0 genotype which constitutes a trap for genetic counseling. We will use molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. The characterization of this GMC is based on the comparison of two sample groups:
Read more
- The test group, with a maximum of 137 individuals carrying 3 copies of the SMN1 gene (suggesting a cis-duplication on one allele)
- The control-1 group, with a maximum of 137 individuals carrying 2 copies of the SMN1 gene
A pilot study performed on 24 samples in the two groups is needed to define the exact sample number necessary for statistical analysis of the study. When the GMC will be characterized, its specificity will be evaluated by testing two sample groups:
- The test group, with 37 individuals carrying 3 copies of the SMN1 gene
- The control-2 group, with 37 individuals carrying 3 copies of the SMN2 gene Molecular combing needs long DNA fibers and usual methods for DNA extraction are not appropriate. This project requires new blood samples for specific DNA extraction.
If this project is successful, during a second project, this GMC will be converted into a simple and cheap PCR-based method. We will then evaluate the sensitivity of this method on our sample collection, notably on individuals with the 2+0 genotype defined by familial genotyping.
- Conditions
- Spinal Muscular Atrophy
- Being tested
- blood sampling
- Medical subject headings
- Muscular Atrophy, Spinal
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingProcedure or surgery
A blood sample will be taken on subject carrying specific genotype
| Study group | Role | What they receive |
|---|---|---|
| Subject carrying 3 copies of the SMN1 gene | Experimental | Using blood sampling, use of molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. Receives: Procedure: blood sampling |
| Subject carrying 2 copies of the SMN1 gene | Other | Using blood sampling, use of molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. Receives: Procedure: blood sampling |
| Subject carrying 3 copies of the SMN2 gene | Other | Using blood sampling, use of molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. Receives: Procedure: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of a genetic signature indicating the presence of one allele with 2 copies in cis of the SMN1 gene.
Measured: Day 1
Secondary outcomes (1)
Specificity of a genetic signature
Specificity of a genetic signature will be done using analysis of individual carrying either 3 copies of the SMN1 gene or 3 copies of the SMN2 gene
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2015 (estimated)
- Study start15 Dec 2015
- Primary completion4 Jul 2016
- Study completion4 Jul 2016
Why it stopped: Financial sponsor difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Muscular AtrophyStudies of the same condition, open and under way.
- More trials run by University Hospital, RouenThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Rouen
- Sponsor type
- University, hospital or other
- Collaborators
- Society GENOMIC VISION
- Responsible party
- Sponsor
- Investigators
- Thierry FREBOURG, MD, Principal investigator, University Hospital, Rouen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02550691
- Sponsor's protocol ID
- 2015/092/HP
- Acronym
- BADGES
- Status last verified
- Jul 2019
- First submitted
- 14 Sep 2015
- Last updated
- 24 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of a Biomarker Associated With Cis-duplication of the SMN1 Gene Aiming at Improving the Genetic Counseling in Spinal Muscular Atrophy Families
- ClinicalTrials.gov ID
- NCT02550691
- Acronym / sponsor ID
- BADGES / 2015/092/HP
- Conditions
- Spinal Muscular Atrophy
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Financial sponsor difficulties
- Enrolment
- 48 participants (actual)
- Lead sponsor
- University Hospital, RouenUniversity, hospital or other
- Collaborators
- Society GENOMIC VISION
- Study start
- 15 Dec 2015 (actual)
- Primary completion
- 4 Jul 2016 (actual)
- Study completion
- 4 Jul 2016 (actual)
- First posted
- 15 Sep 2015 (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.
Spinal Muscular Atrophy (SMA) is a neuromuscular disorder characterized by loss of motor neurons in the anterior horn of the spinal cord and leading to muscle atrophy. SMA has an autosomal recessive inheritance and affects 1 in 6000 infants with a carrier frequency of 1 in 40. In most cases, it is caused by homozygous gene deletion or gene conversion of the SMN1 gene (0+0 genotype) on 5q11-q13. This genomic region has been duplicated and inverted during evolution. Thus the SMN1 gene has a very homologous copy, called SMN2. Genetic counseling aim at detecting carriers with only one copy of the SMN1 gene (0+1 genotype). SMA carrier testing relies on total copy number quantification of the SMN1 copies by quantitative PCR methods. Nevertheless, cis-duplication of the SMN1 gene on one allele and deletion on the second allele (2+0 genotype) can lead to a misinterpretation as molecular methods show 2 copies of the SMN1 gene and cannot detect the carrier status.
The aim of the study is the characterization of a biomarker specific of the cis-duplication of the SMN1 gene in order to allow the detection of this 2+0 genotype which constitutes a trap for genetic counseling. We will use molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. The characterization of this GMC is based on the comparison of two sample groups:
- The test group, with a maximum of 137 individuals carrying 3 copies of the SMN1 gene (suggesting a cis-duplication on one allele)
- The control-1 group, with a maximum of 137 individuals carrying 2 copies of the SMN1 gene
A pilot study performed on 24 samples in the two groups is needed to define the exact sample number necessary for statistical analysis of the study. When the GMC will be characterized, its specificity will be evaluated by testing two sample groups:
- The test group, with 37 individuals carrying 3 copies of the SMN1 gene
- The control-2 group, with 37 individuals carrying 3 copies of the SMN2 gene Molecular combing needs long DNA fibers and usual methods for DNA extraction are not appropriate. This project requires new blood samples for specific DNA extraction.
If this project is successful, during a second project, this GMC will be converted into a simple and cheap PCR-based method. We will then evaluate the sensitivity of this method on our sample collection, notably on individuals with the 2+0 genotype defined by familial genotyping.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Subject carrying 3 copies of the SMN1 gene | Experimental | Procedure: blood samplingUsing blood sampling, use of molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. |
| Subject carrying 2 copies of the SMN1 gene | Other | Procedure: blood samplingUsing blood sampling, use of molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. |
| Subject carrying 3 copies of the SMN2 gene | Other | Procedure: blood samplingUsing blood sampling, use of molecular combing to identify a genomic morse code (GMC) composed of a combination of probes specific of a structural motif on the cis-duplication chromosome. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult individual
- Individual with either 2 copies of the SMN1 gene (control-1 group), 3 copies of the SMN1 gene (test group), or 3 copies of the SMN2 gene (control-2 group).
- Individual with a social insurance
- Signed consent form
Key exclusion criteria (2 listed)
- Pregnant women, nursing women
- Individual without freedom by administrative decision or judicial decision or individual under administrative supervision or legal guardianship
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samplingA blood sample will be taken on subject carrying specific genotype | Procedure or surgery | Subject carrying 2 copies of the SMN1 gene, Subject carrying 3 copies of the SMN1 gene, Subject carrying 3 copies of the SMN2 gene |
Primary outcome
Identification of a genetic signature indicating the presence of one allele with 2 copies in cis of the SMN1 gene.
Time frame: Day 1
1 secondary outcome
Specificity of a genetic signature
Time frame: Day 1
Results and safety
The study was stopped early (reason given: Financial sponsor difficulties). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
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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.
Thierry FREBOURG, MD principal investigator
University Hospital, Rouen
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood sampling in people with Spinal Muscular Atrophy, run by University Hospital, Rouen at 2 sites in France.
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 4 inclusion and 2 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: stopped early, as of the sponsor's last update on 24 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. 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 was stopped early (reason given: Financial sponsor difficulties). Results are not available in the source record.
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?
Identification of a genetic signature indicating the presence of one allele with 2 copies in cis of the SMN1 gene. (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jul 2019.