Spinal Muscular AtrophyNCT05994950
A Review of the Management and Outcomes of Children With SMA in the West Midlands During 2017-2022
An observational study of Spinal Muscular Atrophy, run by Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust at 2 sites in United Kingdom.
Trial summary
Spinal Muscular Atrophy (SMA) is a rare neuromuscular condition, characterised by loss of motor neurons as a result of a mutation in the survival motor neuron gene. This results in muscle wasting and in the most common and severe type, death before 24 months. Read more about this study
- Who is it for?
- Ages 0 to 16 years
- Conditions the study is for
- Spinal Muscular Atrophy
- How many people
- 30 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 6 Dec 2023to 31 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 0 to 16 years
- All sexes
- No healthy volunteers
- Child
Study population: It is important to the methodology of the study that all SMA diagnosed patients known to the services during the timeframe are included in the data collection to evaluate the West Midlands appropriately. The study plans to include a minimum of 30 patients, although the complete patient population known to the service during July 2017- June 2022 that meet the eligibility criteria will be included.
Who may be able to join
- Patient aged <16 years old as of 1st July 2017. (16 years old is the age in which patients typically start their transition process to adulthood - retrospective data collection will stop at the date in which the patient turned 16 years old, if this is before 30th June 2022).
- OR patient was born between 1st July 2017 - 30th June 2022.
- Genetically confirmed 5q SMA.
- Patients must have been under the care of the named Key Collaborative Site and Neuromuscular Service for their SMA anytime during 1st July 2017- 30th June 2022 and must have had at least two clinical reviews during this time.
- Deceased patients can be reviewed, as long as they met the eligibility criteria before their date of death.
Who cannot join
- Aged ≥16 years as of 1st July 2017.
- Genetically confirmed as having non-5q SMA or have no genetic confirmation of their diagnosis.
- Patient was not under the care of the named Key Collaborative Site and Neuromuscular Service for their SMA specialist care anytime during 1st July 2017 - 30th June 2022.
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites, 2 recruiting
- Recruiting
Birmingham Heartlands Hospital
Birmingham, Shropshire, B9 5SS
Deepak Parasuraman, Dr, 01214243759, Deepak.Parasuraman@uhb.nhs.uk
George Gavin, 0121 424 0170, George.Gavin2@uhb.nhs.uk
- Recruiting
The Robert Jones and Agnes Hunt Orthopaedic Hospital
Oswestry, Shropshire, SY10 7AG
Tracey Willis, Prof, 01691 404047, tracey.willis1@nhs.net
Chloe Perry, 01691404139, chloe.perry2@nhs.net
About this study
Spinal Muscular Atrophy (SMA) is a rare neuromuscular condition, characterised by loss of motor neurons as a result of a mutation in the survival motor neuron gene. This results in muscle wasting and in the most common and severe type, death before 24 months. Over the recent years there has been a dynamic shift in the therapeutic options for these patients involving both approved therapies, including gene therapy, and access to clinical trials in genetic modifying.
As a result of this mortality and morbidity have changed particularly for the SMA type 1 population and therefore there is now a changing phenotype with many children needing interventions at different time points compared to the natural history. This review process is a retrospective review from 1st July 2017 - 30th June 2022, when most of the new drug therapies were being introduced, of all the children aged from 0-16 years in the West Midlands region and their outcomes.
Read the detailed description
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterized by degeneration of alpha motor neurons in the spinal cord resulting in progressive muscle wasting, weakness, and paralysis, often leading to early death. It occurs in approximately 1 in 10,000 births. The carrier frequency is variable (between 1:38-1:50) but thought to be highest in Caucasian and Asian populations.
The most common form of SMA is due to a genetic defect in the survival motor neuron 1 (SMN1) gene located on Chromosome 5 (5q11.2-q13.3) which encodes SMN, a protein widely expressed in all eukaryotic cells and necessary for survival of motor neurons. Whilst the diagnosis is made by genetic testing after clinical suspicion, classification is made clinically and on what level of function is achieved, at what age. The severe neonatal type (SMA 0) and the common severe type (SMA I), accounting for approximately 50% cases, presenting before the age of 6 months. These infants, treatment naïve, are very weak and never achieve independent sitting. The rare SMA 0 group generally presents in the neonatal period, often with extreme weakness and contractures and most die within the neonatal period. SMA type II patients present between 6-18 months can achieve independent sitting but are unable to stand and walk and have a reduced life expectancy. SMA type III can be very variable ranging from children who have a similar neuromuscular disability to those with type II, to those that are mildly affected. SMA type IV, the mildest form and very rare, presents in adulthood with onset usually after the second decade, with normal life expectancy. Whilst the sub-groups are classified clinically, there does appear to be a relationship between clinical severity and functional SMN protein and SMN2 copy number. This being said, there has been a phenotypic change since the introduction in the of disease modifying treatment over the last 5 years and therefore the historical classical classification will be evolving. Whilst clinicians have not seen a type I phenotype change to a type II phenotype, many have seen significant changes in mortality and morbidity for these children.
The principle question is how are the West Midlands cohort progressing?
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Spinal Muscular Atrophy, SMA, Paediatric SMA
- Medical subject headings
- Muscular Atrophy, Spinal
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality Rate
The percentage of patients that passed away between 1st July 2017 - 30th June 2022
Measured: 5 years
Change in Children's Hospital Of Philadelphia Infant Test Of Neuromuscular Disorders (CHOP INTEND) score between 1st July 2017 - 30th June 2022
Assessing whether the introduction of SMA specific treatment resulted in a change in the CHOP INTEND score over this 5 year period.
Measured: 5 years
Change in Hammersmith Infant Neurological Examination (HINE) score between 1st July 2017 - 30th June 2022
Assessing whether the introduction of SMA specific treatment resulted in a change in the HINE score over this 5 year period.
Measured: 5 years
Ethnicity
To evaluate whether the patient's ethnicity has an effect on the patient's physical and clinical outcomes.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2023
- Study start6 Dec 2023
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
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.
- 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
- Other
- Time perspective
- Retrospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust
- Sponsor type
- Other government
- Collaborators
- University Hospital Birmingham NHS Foundation Trust
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05994950
- Sponsor's protocol ID
- RL1 874
- Status last verified
- Apr 2024
- First submitted
- 18 Jul 2023
- Last updated
- 12 Apr 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: The anonymised data set and findings may be reported and disseminated through peer reviewed scientific journals and conference reports. No identifiable data will be used at the time of publication, or throughout the analysis of the data. The anonymised data set may be requested by other researchers with appropriate ethical approval.
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Review of the Management and Outcomes of Children With SMA in the West Midlands During 2017-2022
- ClinicalTrials.gov ID
- NCT05994950
- Acronym / sponsor ID
- RL1 874
- Conditions
- Spinal Muscular Atrophy
- Keywords
- Spinal Muscular Atrophy, SMA, Paediatric SMA
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Robert Jones and Agnes Hunt Orthopaedic and District NHS TrustOther government
- Collaborators
- University Hospital Birmingham NHS Foundation Trust
- Study start
- 6 Dec 2023 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 16 Aug 2023 (actual)
- 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 rare neuromuscular condition, characterised by loss of motor neurons as a result of a mutation in the survival motor neuron gene. This results in muscle wasting and in the most common and severe type, death before 24 months. Over the recent years there has been a dynamic shift in the therapeutic options for these patients involving both approved therapies, including gene therapy, and access to clinical trials in genetic modifying.
As a result of this mortality and morbidity have changed particularly for the SMA type 1 population and therefore there is now a changing phenotype with many children needing interventions at different time points compared to the natural history. This review process is a retrospective review from 1st July 2017 - 30th June 2022, when most of the new drug therapies were being introduced, of all the children aged from 0-16 years in the West Midlands region and their outcomes.
Detailed description
Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterized by degeneration of alpha motor neurons in the spinal cord resulting in progressive muscle wasting, weakness, and paralysis, often leading to early death. It occurs in approximately 1 in 10,000 births. The carrier frequency is variable (between 1:38-1:50) but thought to be highest in Caucasian and Asian populations.
The most common form of SMA is due to a genetic defect in the survival motor neuron 1 (SMN1) gene located on Chromosome 5 (5q11.2-q13.3) which encodes SMN, a protein widely expressed in all eukaryotic cells and necessary for survival of motor neurons. Whilst the diagnosis is made by genetic testing after clinical suspicion, classification is made clinically and on what level of function is achieved, at what age. The severe neonatal type (SMA 0) and the common severe type (SMA I), accounting for approximately 50% cases, presenting before the age of 6 months. These infants, treatment naïve, are very weak and never achieve independent sitting. The rare SMA 0 group generally presents in the neonatal period, often with extreme weakness and contractures and most die within the neonatal period. SMA type II patients present between 6-18 months can achieve independent sitting but are unable to stand and walk and have a reduced life expectancy. SMA type III can be very variable ranging from children who have a similar neuromuscular disability to those with type II, to those that are mildly affected. SMA type IV, the mildest form and very rare, presents in adulthood with onset usually after the second decade, with normal life expectancy. Whilst the sub-groups are classified clinically, there does appear to be a relationship between clinical severity and functional SMN protein and SMN2 copy number. This being said, there has been a phenotypic change since the introduction in the of disease modifying treatment over the last 5 years and therefore the historical classical classification will be evolving. Whilst clinicians have not seen a type I phenotype change to a type II phenotype, many have seen significant changes in mortality and morbidity for these children.
The principle question is how are the West Midlands cohort progressing?
Study design
- Observational model
- Other
- Time perspective
- Retrospective
Who may qualify
- Ages
- 0 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- It is important to the methodology of the study that all SMA diagnosed patients known to the services during the timeframe are included in the data collection to evaluate the West Midlands appropriately. The study plans to include a minimum of 30 patients, although the complete patient population known to the service during July 2017- June 2022 that meet the eligibility criteria will be included.
Key inclusion criteria (5 listed)
- Patient aged <16 years old as of 1st July 2017. (16 years old is the age in which patients typically start their transition process to adulthood - retrospective data collection will stop at the date in which the patient turned 16 years old, if this is before 30th June 2022).
- OR patient was born between 1st July 2017 - 30th June 2022.
- Genetically confirmed 5q SMA.
- Patients must have been under the care of the named Key Collaborative Site and Neuromuscular Service for their SMA anytime during 1st July 2017- 30th June 2022 and must have had at least two clinical reviews during this time.
- Deceased patients can be reviewed, as long as they met the eligibility criteria before their date of death.
Key exclusion criteria (3 listed)
- Aged ≥16 years as of 1st July 2017.
- Genetically confirmed as having non-5q SMA or have no genetic confirmation of their diagnosis.
- Patient was not under the care of the named Key Collaborative Site and Neuromuscular Service for their SMA specialist care anytime during 1st July 2017 - 30th June 2022.
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
Mortality Rate
Time frame: 5 years
The percentage of patients that passed away between 1st July 2017 - 30th June 2022
Change in Children's Hospital Of Philadelphia Infant Test Of Neuromuscular Disorders (CHOP INTEND) score between 1st July 2017 - 30th June 2022
Time frame: 5 years
Assessing whether the introduction of SMA specific treatment resulted in a change in the CHOP INTEND score over this 5 year period.
Change in Hammersmith Infant Neurological Examination (HINE) score between 1st July 2017 - 30th June 2022
Time frame: 5 years
Assessing whether the introduction of SMA specific treatment resulted in a change in the HINE score over this 5 year period.
Ethnicity
Time frame: 5 years
To evaluate whether the patient's ethnicity has an effect on the patient's physical and clinical outcomes.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2024.
- Individual participant dataSharing planned: No. The anonymised data set and findings may be reported and disseminated through peer reviewed scientific journals and conference reports. No identifiable data will be used at the time of publication, or throughout the analysis of the data. The anonymised data set may be requested by other researchers with appropriate ethical approval.
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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.
2 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, run by Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust at 2 sites in United Kingdom.
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 5 inclusion and 3 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: status not confirmed, as of the sponsor's last update on 12 Apr 2024. 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 United Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Professor Tracey Willis (01691404047, tracey.willis1@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality Rate (time frame: 5 years). The study lists 4 primary outcomes in all. 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 12 Apr 2024.