xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05994950</url>
    </required_header>
    <id_info>
      <org_study_id>RL1 874</org_study_id>
      <nct_id>NCT05994950</nct_id>
    </id_info>
    <brief_title>A Review of the Management and Outcomes of Children With SMA in the West Midlands During 2017-2022</brief_title>
    <official_title>A Review of the Management and Outcomes of Children With SMA in the West Midlands During 2017-2022</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University Hospital Birmingham NHS Foundation Trust</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Spinal Muscular Atrophy (SMA) is a rare neuromuscular condition, characterised by loss of&#xD;
        motor neurons as a result of a mutation in the survival motor neuron gene. This results in&#xD;
        muscle wasting and in the most common and severe type, death before 24 months. Over the&#xD;
        recent years there has been a dynamic shift in the therapeutic options for these patients&#xD;
        involving both approved therapies, including gene therapy, and access to clinical trials in&#xD;
        genetic modifying.&#xD;
  &#xD;
        As a result of this mortality and morbidity have changed particularly for the SMA type 1&#xD;
        population and therefore there is now a changing phenotype with many children needing&#xD;
        interventions at different time points compared to the natural history. This review process&#xD;
        is a retrospective review from 1st July 2017 - 30th June 2022, when most of the new drug&#xD;
        therapies were being introduced, of all the children aged from 0-16 years in the West&#xD;
        Midlands region and their outcomes.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterized by degeneration&#xD;
        of alpha motor neurons in the spinal cord resulting in progressive muscle wasting, weakness,&#xD;
        and paralysis, often leading to early death. It occurs in approximately 1 in 10,000 births.&#xD;
        The carrier frequency is variable (between 1:38-1:50) but thought to be highest in Caucasian&#xD;
        and Asian populations.&#xD;
  &#xD;
        The most common form of SMA is due to a genetic defect in the survival motor neuron 1 (SMN1)&#xD;
        gene located on Chromosome 5 (5q11.2-q13.3) which encodes SMN, a protein widely expressed in&#xD;
        all eukaryotic cells and necessary for survival of motor neurons. Whilst the diagnosis is&#xD;
        made by genetic testing after clinical suspicion, classification is made clinically and on&#xD;
        what level of function is achieved, at what age. The severe neonatal type (SMA 0) and the&#xD;
        common severe type (SMA I), accounting for approximately 50% cases, presenting before the age&#xD;
        of 6 months. These infants, treatment naïve, are very weak and never achieve independent&#xD;
        sitting. The rare SMA 0 group generally presents in the neonatal period, often with extreme&#xD;
        weakness and contractures and most die within the neonatal period. SMA type II patients&#xD;
        present between 6-18 months can achieve independent sitting but are unable to stand and walk&#xD;
        and have a reduced life expectancy. SMA type III can be very variable ranging from children&#xD;
        who have a similar neuromuscular disability to those with type II, to those that are mildly&#xD;
        affected. SMA type IV, the mildest form and very rare, presents in adulthood with onset&#xD;
        usually after the second decade, with normal life expectancy. Whilst the sub-groups are&#xD;
        classified clinically, there does appear to be a relationship between clinical severity and&#xD;
        functional SMN protein and SMN2 copy number. This being said, there has been a phenotypic&#xD;
        change since the introduction in the of disease modifying treatment over the last 5 years and&#xD;
        therefore the historical classical classification will be evolving. Whilst clinicians have&#xD;
        not seen a type I phenotype change to a type II phenotype, many have seen significant changes&#xD;
        in mortality and morbidity for these children.&#xD;
  &#xD;
        The principle question is how are the West Midlands cohort progressing?&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">December 31, 2023</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Other</observational_model>
      <time_perspective>Retrospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Mortality Rate</measure>
      <time_frame>5 years</time_frame>
      <description>The percentage of patients that passed away between 1st July 2017 - 30th June 2022</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Children's Hospital Of Philadelphia Infant Test Of Neuromuscular Disorders (CHOP INTEND) score between 1st July 2017 - 30th June 2022</measure>
      <time_frame>5 years</time_frame>
      <description>Assessing whether the introduction of SMA specific treatment resulted in a change in the CHOP INTEND score over this 5 year period.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in Hammersmith Infant Neurological Examination (HINE) score between 1st July 2017 - 30th June 2022</measure>
      <time_frame>5 years</time_frame>
      <description>Assessing whether the introduction of SMA specific treatment resulted in a change in the HINE score over this 5 year period.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Ethnicity</measure>
      <time_frame>5 years</time_frame>
      <description>To evaluate whether the patient's ethnicity has an effect on the patient's physical and clinical outcomes.</description>
    </primary_outcome>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Spinal Muscular Atrophy</condition>
    <eligibility>
      <study_pop>
        <textblock>
          It is important to the methodology of the study that all SMA diagnosed patients known to&#xD;
          the services during the timeframe are included in the data collection to evaluate the West&#xD;
          Midlands appropriately. The study plans to include a minimum of 30 patients, although the&#xD;
          complete patient population known to the service during July 2017- June 2022 that meet the&#xD;
          eligibility criteria will be included.&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patient aged &lt;16 years old as of 1st July 2017. (16 years old is the age in which&#xD;
               patients typically start their transition process to adulthood - retrospective data&#xD;
               collection will stop at the date in which the patient turned 16 years old, if this is&#xD;
               before 30th June 2022).&#xD;
  &#xD;
            -  OR patient was born between 1st July 2017 - 30th June 2022.&#xD;
  &#xD;
            -  Genetically confirmed 5q SMA.&#xD;
  &#xD;
            -  Patients must have been under the care of the named Key Collaborative Site and&#xD;
               Neuromuscular Service for their SMA anytime during 1st July 2017- 30th June 2022 and&#xD;
               must have had at least two clinical reviews during this time.&#xD;
  &#xD;
            -  Deceased patients can be reviewed, as long as they met the eligibility criteria before&#xD;
               their date of death.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Aged ≥16 years as of 1st July 2017.&#xD;
  &#xD;
            -  Genetically confirmed as having non-5q SMA or have no genetic confirmation of their&#xD;
               diagnosis.&#xD;
  &#xD;
            -  Patient was not under the care of the named Key Collaborative Site and Neuromuscular&#xD;
               Service for their SMA specialist care anytime during 1st July 2017 - 30th June 2022.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>0 Years</minimum_age>
      <maximum_age>16 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Professor Tracey Willis</last_name>
      <phone>01691404047</phone>
      <email>tracey.willis1@nhs.net</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Chloe Perry</last_name>
      <phone>01691404139</phone>
      <email>chloe.perry2@nhs.net</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 15, 2023</last_update_submitted>
    <last_update_submitted_qc>August 15, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Spinal Muscular Atrophy</keyword>
    <keyword>SMA</keyword>
    <keyword>Paediatric SMA</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Muscular Atrophy</mesh_term>
      <mesh_term>Muscular Atrophy, Spinal</mesh_term>
      <mesh_term>Atrophy</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_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.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05994950
  org study id: RL1 874
  nct id: NCT05994950
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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?
  observational model: Other
  time perspective: Retrospective
  measure: Mortality Rate
  time frame: 5 years
  description: The percentage of patients that passed away between 1st July 2017 - 30th June 2022
  measure: 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
  description: Assessing whether the introduction of SMA specific treatment resulted in a change in the CHOP INTEND score over this 5 year period.
  measure: Change in Hammersmith Infant Neurological Examination (HINE) score between 1st July 2017 - 30th June 2022
  time frame: 5 years
  description: Assessing whether the introduction of SMA specific treatment resulted in a change in the HINE score over this 5 year period.
  measure: Ethnicity
  time frame: 5 years
  description: To evaluate whether the patient's ethnicity has an effect on the patient's physical and clinical outcomes.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 0 Years
  maximum age: 16 Years
  healthy volunteers: No
  last name: Professor Tracey Willis
  phone: 01691404047
  email: tracey.willis1@nhs.net
  last name: Chloe Perry
  phone: 01691404139
  email: chloe.perry2@nhs.net
  responsible party type: Sponsor
  mesh term: Muscular Atrophy
  mesh term: Muscular Atrophy, Spinal
  mesh term: Atrophy
  sharing ipd: No
  ipd 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.