Muscular Atrophy, Spinal Clinical Trial
— SMA-NBSOfficial title:
Population-based New-Born Screening of Spinal Muscular Atrophy to Evaluate the Uptake and Feasibility in the UK Context
NCT number | NCT05481164 |
Other study ID # | Oxford |
Secondary ID | |
Status | Recruiting |
Phase | |
First received | |
Last updated | |
Start date | March 8, 2022 |
Est. completion date | March 7, 2025 |
Spinal muscular atrophy (SMA) is a rare, treatable, genetic disease that typically occurs in infancy and early childhood. SMA progressively, and irreversibly, destroys motor neurons in the brainstem and spinal cord, which control movement, in turn leading to deterioration or loss of muscle strength. This can begin during the first 3 months of a child's life, and in those with the most common and severe type of SMA, 95% of all motor neurons can be lost before the age of 6 months. The majority of children with this type of SMA, if untreated, will not survive beyond 2 years of age without permanent ventilatory support. Of those who do, many will not achieve independent sitting and few walk independently. A challenging aspect of treating SMA is the delay in its diagnosis, usually after disease onset. Diagnosis usually occurs when the affected child presents clinical symptoms, by which point a significant portion of their motor neurons will have been irreversibly lost. In contrast, infants and children with SMA who are identified and treated at an early stage, especially those treated pre-symptomatically, show much better motor development. Given that SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1), it can be detected via genetic testing before a child presents with clinical symptoms. This lends itself to newborn genetic screening, through which pre-symptomatic diagnosis of SMA can be made as early as possible, providing the opportunity for substantially enhanced therapeutic effects and outcomes. The aim and objective of this screening study is to assess the uptake, reliability, and feasibility of neonatal screening for SMA in a UK setting. It is hoped that by doing so it will help establish the early detection, diagnosis, and access to the recently available therapeutic options for SMA.Screening will be done through the routine UK newborn blood spot screening pathway, using spare capacity from a newborns' Guthrie card (dried blood spot sample). A major objective of the design of this protocol and the processes it describes, together with the staff funding secured, has been to ensure that it will not interfere with the standard screening procedure in any way.Recruitment will be carried out in the maternity units of four hospital trusts in the Thames Valley: Oxford University Hospitals NHS Trust, Royal Berkshire NHS Foundation Trust, Milton Keynes University Hospital NHS Foundation Trust, and Buckinghamshire Healthcare NHS Trust.
Status | Recruiting |
Enrollment | 45000 |
Est. completion date | March 7, 2025 |
Est. primary completion date | March 7, 2025 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 16 Years and older |
Eligibility | Inclusion Criteria: - Whose mother is undergoing antenatal care at one of the four Hospital Trusts in the Thames Valley region, whose blood spot will be screened at the NHS Oxford Regenial Genetics Laboratory - Whose mother is able to understand the participant information sheet and is willing to provide her informed consent. - Whose mother is in the second or third trimester of pregnancy (=18 weeks' gestation), or up to 28 days postnatal (the latter is consistent with the World Health Organisation's definition of a newborn infant or neonate) Exclusion Criteria: - Whose mother is unable to understand written or verbal English which would preclude them from understanding the study |
Country | Name | City | State |
---|---|---|---|
United Kingdom | Buckinghamshire HealthCare Trust | Buckingham | |
United Kingdom | Milton Keynes University Hospital NHS Foundation Trust | Milton Keynes | |
United Kingdom | University of Oxford UK | Oxford | |
United Kingdom | St Mary's Maternity Hospital | Poole | |
United Kingdom | Queen Alexandra Hospital | Portsmouth | |
United Kingdom | Royal Berkshire NHS Foundation Trust | Reading | |
United Kingdom | Salisbury District Hospital | Salisbury | |
United Kingdom | Princess Anne Hospital | Southampton |
Lead Sponsor | Collaborator |
---|---|
University of Oxford | Hoffmann-La Roche, Novartis Gene Therapies, Oxford University Hospitals NHS Trust |
United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | To evaluate whether treatment can be delivered in a timely fashion, consistent with what global SMA screening studies have shown to be able to facilitate | The time passed between the birth of diagnostic-positive newborns to the initiation of their SMA treatment | All outcome measures will be assessed intermittently over the course of the 36 month period of the study | |
Other | To evaluate logistic and cost of SMA screening | Human Resources (FTE) and cost associated with NBS | This will be assessed at the end of the 3 year study | |
Primary | To assess the uptake of newborn bloodspot genetic screening for spinal muscular atrophy among expectant and delivered mothers over the course of the 36 month study | The number of approached mothers
The number of consented mothers The proportion of approached mothers consenting to take part in the study, measured by the number of consented mothers divided by the combined total of consented and approached mothers (times 100%) The number of SMA samples processed at the NHS neonatal and antenatal Screening Laboratory at the John Radcliffe Hospital |
All outcome measures will be assessed intermittently over the course of the 36 month period of the study | |
Secondary | To determine the feasibility and reliability of the study screening test and regimen in identifying true positive cases | The number of false positive results
The positive predictive value- the probability that newborns who receive a screen-positive result from the study are actually affected by spinal muscular atrophy - measured by the number of true-positive newborns divided by the combined total of true-positive |
All outcome measures will be assessed intermittently over the course of the 36 month period of the study | |
Secondary | To determine the feasibility and reliability of the study screening test and regimen in identifying true negative cases | The number of false negative results identified in the Thames Valley and who have actually been screened negative
The specificity value - the ability of the study screening test and regimen to correctly generate a screen-negative result for newborns who are actually not affected by spinal muscular atrophy - measured by the number of true-negative newborns divided by the combined total of true-negative and false-positive newborns (times 100%) |
All outcome measures will be assessed intermittently over the course of the 36 month period of the study | |
Secondary | To evaluate the feasibility of performing spinal muscular atrophy screening on newborn dried blood spot with the goal of facilitating early diagnosis of SMA in a UK NBS pathway | The time passed between the birth of newborns to the availability of their SMA screening results | All outcome measures will be assessed intermittently over the course of the 36 month period of the study | |
Secondary | To investigate the epidemiology of spinal muscular atrophy in the Thames Valley | The incidence of SMA, measured by the number of diagnostic-positive newborns from the study population divided by the total study population during the study period
The number of SMN2 gene copies and their distribution among diagnostic-positive newborns |
This will be assessed at the end of the 3 year study |
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