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A Review of the Management and Outcomes of Children With SMA in the West Midlands During 2017-2022

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ClinicalTrials.gov Identifier: NCT05994950
Recruitment Status : Recruiting
First Posted : August 16, 2023
Last Update Posted : April 12, 2024
Sponsor:
Collaborator:
University Hospital Birmingham NHS Foundation Trust
Information provided by (Responsible Party):
Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust

Study Description
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Brief 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. 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.


Condition or disease
Spinal Muscular Atrophy

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
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Study Type : Observational
Estimated Enrollment : 30 participants
Observational Model: Other
Time Perspective: Retrospective
Official Title: A Review of the Management and Outcomes of Children With SMA in the West Midlands During 2017-2022
Actual Study Start Date : December 6, 2023
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Outcome Measures
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Primary Outcome Measures :
  1. Mortality Rate [ Time Frame: 5 years ]
    The percentage of patients that passed away between 1st July 2017 - 30th June 2022

  2. 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.

  3. 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.

  4. Ethnicity [ Time Frame: 5 years ]
    To evaluate whether the patient's ethnicity has an effect on the patient's physical and clinical outcomes.


Eligibility Criteria
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Ages Eligible for Study:   0 Years to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
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.
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05994950


Contacts
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Contact: Professor Tracey Willis 01691404047 tracey.willis1@nhs.net
Contact: Chloe Perry 01691404139 chloe.perry2@nhs.net

Locations
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United Kingdom
Birmingham Heartlands Hospital Recruiting
Birmingham, Shropshire, United Kingdom, B9 5SS
Contact: Deepak Parasuraman, Dr    01214243759    Deepak.Parasuraman@uhb.nhs.uk   
Contact: George Gavin    0121 424 0170    George.Gavin2@uhb.nhs.uk   
The Robert Jones and Agnes Hunt Orthopaedic Hospital Recruiting
Oswestry, Shropshire, United Kingdom, SY10 7AG
Contact: Tracey Willis, Prof    01691 404047    tracey.willis1@nhs.net   
Contact: Chloe Perry    01691404139    chloe.perry2@nhs.net   
Sponsors and Collaborators
Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust
University Hospital Birmingham NHS Foundation Trust
More Information
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Responsible Party: Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust
ClinicalTrials.gov Identifier: NCT05994950    
Other Study ID Numbers: RL1 874
First Posted: August 16, 2023    Key Record Dates
Last Update Posted: April 12, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: 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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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust:
Spinal Muscular Atrophy
SMA
Paediatric SMA
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Atrophy
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
 Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases