Spinal Muscular AtrophyNCT02532244
Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
An observational study of Spinal Muscular Atrophy and Charcot-Marie-Tooth Disease, run by Nemours Children's Clinic at 3 sites in United States.
Trial summary
The goal of this study is to establish a genetic registry of patients with early-onset motor neuron and neuromuscular diseases. The investigators will collect samples from patients with a motor neuron or a neuromuscular disorder and their family members. Read more about this study
- Who is it for?
- Ages 1 month and olderHealthy volunteers can take part
- Conditions the study is for
- Spinal Muscular Atrophy, Charcot-Marie-Tooth Disease, Muscular Dystrophy
- What is being tested?
- sample collection
- How many people
- 230 participants
- Where
- 3 sitesUnited States
- Study dates
- Jun 2015to 18 Dec 2024
- 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 1 month and older
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: This study will enroll children diagnosed with a motor neuron or neuromuscular disease as well as their parents and/or siblings as well as adults with childhood-onset motor neuron or neuromuscular diseases.
Who may be able to join
- Diagnosis of motor neuron/neuromuscular disease confirmed by neurologist
- Be seen by one of the study investigators
Who cannot join
- not seen by one of the study investigators
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Nemours Children's Specialty Care
Jacksonville, Florida, 32207
Nemours Children's Hospital Orlando
Orlando, Florida, 32827
Nemours Children's Hospital Delaware
Wilmington, Delaware, 19803
About this study
The goal of this study is to establish a genetic registry of patients with early-onset motor neuron and neuromuscular diseases. The investigators will collect samples from patients with a motor neuron or a neuromuscular disorder and their family members. The samples to be collected will be obtained using minimally invasive (whole blood) means. The research team will then extract high quality genomic DNA or RNA from these samples and use it to identify and confirm novel gene mutations and to identify genes which regulate the severity of motor neuron/neuromuscular diseases.
Read the detailed description
Diseases affecting the motor unit--which is composed of the motor neuron, its myelin sheath and its innervated muscle fibers--are a diverse, heterogeneous group having heterogeneous clinical presentations and genetic causes. Many of these disorders have a inherited component. In some cases, the genetics underlying a given neuromuscular/motor neuron disease, like spinal muscular atrophy (SMA) or Duchenne muscular dystrophy, are well characterized. There are, however, disorders whose genetic basis has yet to be determined or genetically characterized diseases which harbor novel mutations. The purpose of this genetic registry is to catalogue early-onset motor neuron and neuromuscular disorders and to determine their genetic bases. With samples obtained from this registry, the investigators will be able to provide a genetic diagnosis for a specific neuromuscular/motor neuron disease which will lead to better care for those patients affected by these diseases.
Many of these disorders have a wide spectrum of phenotypic variability. For example, the severity of SMA is quite variable even though it is caused by the loss of a single gene, i.e. survival motor neuron 1 (SMN1). The number of copies of the duplicated gene survival motor neuron 2 (SMN2) dictates phenotypic severity in SMA. In this study, the research team will also identify potential modifiers of phenotypic severity for specific disorders like SMA and Charcot-Marie-Tooth (CMT) disease. With the identification of novel modifier genes, the investigators will be able to more accurately predict disease outcomes and the investigators will also have novel targets for the development of therapeutic agents for these diseases.
- Conditions
- Spinal Muscular Atrophy, Charcot-Marie-Tooth Disease, Muscular Dystrophy, Spinal Muscular Atrophy With Respiratory Distress 1, Amyotrophic Lateral Sclerosis, Motor Neuron Disease
- Being tested
- sample collection
- Keywords
- distal hereditary motor neuronopathy
- Medical subject headings
- Muscular Atrophy, Spinal, Charcot-Marie-Tooth Disease, Muscular Dystrophies, Spinal muscular atrophy with respiratory distress 1, Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Neuromuscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sample collectionOther
collection of blood
| Study group | Role | What they receive |
|---|---|---|
| sample collection | Each participant will have blood drawn for genetic analysis and for establishment of a lymphoblastoid cell line. Receives: Other: sample collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
genetic diagnosis
The genetic basis for the subject's condition will be verified/determined by Sanger sequencing of DNA sample
Measured: up to 2 years
Secondary outcomes (4)
SMN1 copy number
The number of copies of the SMN1 gene will be determined using array digital polymerase chain reaction (PCR).
Measured: up to 2 years
SMN2 copy number
The number of copies of the SMN2 gene will be determined using array digital PCR.
Measured: up to 2 years
target gene mRNA levels
The relative levels of the disease gene-specific messenger ribonucleic acid (mRNA) will be measured using quantitative PCR.
Measured: up to 2 years
target gene protein levels
The relative amounts of the disease-gene-specific protein will be measured using immunoblot.
Measured: up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2015 (estimated)
- Study startJun 2015
- Primary completion18 Dec 2024
- Study completion18 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)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
- Case only
- Time perspective
- Prospective
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthew E. R. Butchbach, Ph.D., Nemours Children's Clinic
- Investigators
- Matthew ER Butchbach, Ph.D., Principal investigator, Nemours Children's Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02532244
- Sponsor's protocol ID
- 764456
- Status last verified
- Dec 2024
- First submitted
- 21 Aug 2015
- Last updated
- 19 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: De-identified information will be shared once the data are published.
Publications
Stabley DL, Holbrook J, Harris AW, Swoboda KJ, Crawford TO, Sol-Church K, Butchbach MER. Establishing a reference dataset for the authentication of spinal muscular atrophy cell lines using STR profiling and digital PCR. Neuromuscul Disord. 2017 May;27(5):439-446. doi: 10.1016/j.nmd.2017.02.002. Epub 2017 Feb 6.
PubMed 28284873Stabley DL, Harris AW, Holbrook J, Chubbs NJ, Lozo KW, Crawford TO, Swoboda KJ, Funanage VL, Wang W, Mackenzie W, Scavina M, Sol-Church K, Butchbach ME. SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR. Mol Genet Genomic Med. 2015 Jul;3(4):248-57. doi: 10.1002/mgg3.141. Epub 2015 Mar 21.
PubMed 26247043Chen X, Sanchis-Juan A, French CE, Connell AJ, Delon I, Kingsbury Z, Chawla A, Halpern AL, Taft RJ; NIHR BioResource; Bentley DR, Butchbach MER, Raymond FL, Eberle MA. Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data. Genet Med. 2020 May;22(5):945-953. doi: 10.1038/s41436-020-0754-0. Epub 2020 Feb 18.
PubMed 32066871Jiang L, Lin R, Gallagher S, Zayac A, Butchbach MER, Hung P. Development and validation of a 4-color multiplexing spinal muscular atrophy (SMA) genotyping assay on a novel integrated digital PCR instrument. Sci Rep. 2020 Nov 16;10(1):19892. doi: 10.1038/s41598-020-76893-7.
PubMed 33199817Stabley DL, Holbrook J, Scavina M, Crawford TO, Swoboda KJ, Robbins KM, Butchbach MER. Detection of SMN1 to SMN2 gene conversion events and partial SMN1 gene deletions using array digital PCR. Neurogenetics. 2021 Mar;22(1):53-64. doi: 10.1007/s10048-020-00630-5. Epub 2021 Jan 7.
PubMed 33415588Pinto A, Cunha C, Chaves R, Butchbach MER, Adega F. Comprehensive In Silico Analysis of Retrotransposon Insertions within the Survival Motor Neuron Genes Involved in Spinal Muscular Atrophy. Biology (Basel). 2022 May 27;11(6):824. doi: 10.3390/biology11060824.
PubMed 35741345
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
- ClinicalTrials.gov ID
- NCT02532244
- Acronym / sponsor ID
- 764456
- Conditions
- Spinal Muscular Atrophy, Charcot-Marie-Tooth Disease, Muscular Dystrophy, Spinal Muscular Atrophy With Respiratory Distress 1, Amyotrophic Lateral Sclerosis, Motor Neuron Disease
- Keywords
- distal hereditary motor neuronopathy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 230 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Study start
- Jun 2015 (actual)
- Primary completion
- 18 Dec 2024 (actual)
- Study completion
- 18 Dec 2024 (actual)
- First posted
- 25 Aug 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.
The goal of this study is to establish a genetic registry of patients with early-onset motor neuron and neuromuscular diseases. The investigators will collect samples from patients with a motor neuron or a neuromuscular disorder and their family members. The samples to be collected will be obtained using minimally invasive (whole blood) means. The research team will then extract high quality genomic DNA or RNA from these samples and use it to identify and confirm novel gene mutations and to identify genes which regulate the severity of motor neuron/neuromuscular diseases.
Detailed description
Diseases affecting the motor unit--which is composed of the motor neuron, its myelin sheath and its innervated muscle fibers--are a diverse, heterogeneous group having heterogeneous clinical presentations and genetic causes. Many of these disorders have a inherited component. In some cases, the genetics underlying a given neuromuscular/motor neuron disease, like spinal muscular atrophy (SMA) or Duchenne muscular dystrophy, are well characterized. There are, however, disorders whose genetic basis has yet to be determined or genetically characterized diseases which harbor novel mutations. The purpose of this genetic registry is to catalogue early-onset motor neuron and neuromuscular disorders and to determine their genetic bases. With samples obtained from this registry, the investigators will be able to provide a genetic diagnosis for a specific neuromuscular/motor neuron disease which will lead to better care for those patients affected by these diseases.
Many of these disorders have a wide spectrum of phenotypic variability. For example, the severity of SMA is quite variable even though it is caused by the loss of a single gene, i.e. survival motor neuron 1 (SMN1). The number of copies of the duplicated gene survival motor neuron 2 (SMN2) dictates phenotypic severity in SMA. In this study, the research team will also identify potential modifiers of phenotypic severity for specific disorders like SMA and Charcot-Marie-Tooth (CMT) disease. With the identification of novel modifier genes, the investigators will be able to more accurately predict disease outcomes and the investigators will also have novel targets for the development of therapeutic agents for these diseases.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sample collection | – | Other: sample collectionEach participant will have blood drawn for genetic analysis and for establishment of a lymphoblastoid cell line. |
Who may qualify
- Ages
- 1 month and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- This study will enroll children diagnosed with a motor neuron or neuromuscular disease as well as their parents and/or siblings as well as adults with childhood-onset motor neuron or neuromuscular diseases.
Key inclusion criteria (2 listed)
- Diagnosis of motor neuron/neuromuscular disease confirmed by neurologist
- Be seen by one of the study investigators
Key exclusion criteria (1 listed)
- not seen by one of the study investigators
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 |
|---|---|---|
| sample collectioncollection of blood | Other | sample collection |
Primary outcome
genetic diagnosis
Time frame: up to 2 years
The genetic basis for the subject's condition will be verified/determined by Sanger sequencing of DNA sample
4 secondary outcomes
SMN1 copy number
Time frame: up to 2 years
SMN2 copy number
Time frame: up to 2 years
target gene mRNA levels
Time frame: up to 2 years
target gene protein levels
Time frame: up to 2 years
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 19 Dec 2024.
- Results publication: PubMed 28284873Stabley DL, Holbrook J, Harris AW, Swoboda KJ, Crawford TO, Sol-Church K, Butchbach MER. Establishing a reference dataset for the authentication of spinal muscular atrophy cell lines using STR profiling and digital PCR. Neuromuscul Disord. 2017 May;27(5):439-446. doi: 10.1016/j.nmd.2017.02.002. Epub 2017 Feb 6.
- Results publication: PubMed 26247043Stabley DL, Harris AW, Holbrook J, Chubbs NJ, Lozo KW, Crawford TO, Swoboda KJ, Funanage VL, Wang W, Mackenzie W, Scavina M, Sol-Church K, Butchbach ME. SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR. Mol Genet Genomic Med. 2015 Jul;3(4):248-57. doi: 10.1002/mgg3.141. Epub 2015 Mar 21.
- Results publication: PubMed 32066871Chen X, Sanchis-Juan A, French CE, Connell AJ, Delon I, Kingsbury Z, Chawla A, Halpern AL, Taft RJ; NIHR BioResource; Bentley DR, Butchbach MER, Raymond FL, Eberle MA. Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data. Genet Med. 2020 May;22(5):945-953. doi: 10.1038/s41436-020-0754-0. Epub 2020 Feb 18.
- Results publication: PubMed 33199817Jiang L, Lin R, Gallagher S, Zayac A, Butchbach MER, Hung P. Development and validation of a 4-color multiplexing spinal muscular atrophy (SMA) genotyping assay on a novel integrated digital PCR instrument. Sci Rep. 2020 Nov 16;10(1):19892. doi: 10.1038/s41598-020-76893-7.
- Results publication: PubMed 33415588Stabley DL, Holbrook J, Scavina M, Crawford TO, Swoboda KJ, Robbins KM, Butchbach MER. Detection of SMN1 to SMN2 gene conversion events and partial SMN1 gene deletions using array digital PCR. Neurogenetics. 2021 Mar;22(1):53-64. doi: 10.1007/s10048-020-00630-5. Epub 2021 Jan 7.
- Results publication: PubMed 35741345Pinto A, Cunha C, Chaves R, Butchbach MER, Adega F. Comprehensive In Silico Analysis of Retrotransposon Insertions within the Survival Motor Neuron Genes Involved in Spinal Muscular Atrophy. Biology (Basel). 2022 May 27;11(6):824. doi: 10.3390/biology11060824.
- Individual participant dataSharing planned: Undecided. De-identified information will be shared once the data are published.
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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.
Matthew ER Butchbach, Ph.D. principal investigator
Nemours Children's Clinic
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Spinal Muscular Atrophy and Charcot-Marie-Tooth Disease, run by Nemours Children's Clinic at 3 sites in United States.
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 1 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 19 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
genetic diagnosis (time frame: up to 2 years). 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 NCT02532244, which also lists 6 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 19 Dec 2024.