Newborn Screening for Spinal Muscular Atrophy

NCT05481164 | Completed

• 1 other identifier: Oxford
• Study Type: observational
• Target: 33,568
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Muscular Atrophy, Spinal

Outcome Measures

Primary Outcomes (1)

• 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

  1. The number of approached mothers 2. The number of consented mothers 3. 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%) 4. 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 Outcomes (4)

• To determine the feasibility and reliability of the study screening test and regimen in identifying true positive cases

  All outcome measures will be assessed intermittently over the course of the 36 month period of the study

• To determine the feasibility and reliability of the study screening test and regimen in identifying true negative cases

  All outcome measures will be assessed intermittently over the course of the 36 month period of the study

• 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

  All outcome measures will be assessed intermittently over the course of the 36 month period of the study

• To investigate the epidemiology of spinal muscular atrophy in the Thames Valley

  This will be assessed at the end of the 3 year study

Other Outcomes (2)

• 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

  All outcome measures will be assessed intermittently over the course of the 36 month period of the study

• To evaluate logistic and cost of SMA screening

  This will be assessed at the end of the 3 year study

Study Arms (1)

Screen for Spinal Muscular atrophy for newborns

Babies with an SMA screen-positive result

Eligibility Criteria

• Age: 16 Years+
• Gender Eligibility Details: Women who are pregnant.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Pregnant women

You may qualify if:

• 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)

You may not qualify if:

• Whose mother is unable to understand written or verbal English which would preclude them from understanding the study

Sponsors & Collaborators

• University of Oxford: lead
• Novartis Gene Therapies: collaborator
• Hoffmann-La Roche: collaborator
• Oxford University Hospitals NHS Trust: collaborator

Study Sites (9)

Buckinghamshire HealthCare Trust

Buckingham, United Kingdom

Location

Dorset County Hospital (DCHFT)

Dorchester, DT1 2JY, United Kingdom

Location

Milton Keynes University Hospital NHS Foundation Trust

Milton Keynes, United Kingdom

Location

University of Oxford UK

Oxford, United Kingdom

Location

St Mary's Maternity Hospital

Poole, United Kingdom

Location

Queen Alexandra Hospital

Portsmouth, United Kingdom

Location

Royal Berkshire NHS Foundation Trust

Reading, United Kingdom

Location

Salisbury District Hospital

Salisbury, United Kingdom

Location

Princess Anne Hospital

Southampton, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

an automated multi-hole punching machine generates samples (discs) from the dried blood spots on the Guthrie card, to be used in the routine screening of conditions included in national NHS newborn blood spot screening programme. DNA will be extracted from the sample and run on a sensitive assay called qPCR, which will allow us to detect the presence of the affected gene in SMA, called SMN1.

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2022
• First Posted: August 1, 2022
• Study Start: March 8, 2022
• Primary Completion: December 31, 2024
• Study Completion: July 31, 2025
• Last Updated: November 20, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (9)