<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/NCT04404764</url>
  </required_header>
  <id_info>
    <org_study_id>27245419.0.0000.5259</org_study_id>
    <nct_id>NCT04404764</nct_id>
  </id_info>
  <brief_title>Characterization of the Clinical-epidemiological Profile of Patients With SMA5q Types II and III: Observational Study</brief_title>
  <official_title>Characterization of the Clinical-epidemiological Profile of Patients With Spinal Muscular Atrophy (SMA) 5q Types II and III in Follow-up in the Brazilian Unified Public Health System: A Cross-sectional Observational Study (Registry)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital Israelita Albert Einstein</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, Brazil</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital Israelita Albert Einstein</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to characterize the clinical-epidemiological profile and baseline&#xD;
      characteristics of patients with spinal muscular atrophy (SMA) 5q types II and III in&#xD;
      follow-up at the Brazilian Unified Public Health System (SUS). The study data will be based&#xD;
      on patients´ medical records from several Brazilian public hospitals, which will be defined&#xD;
      by the Brazilian Ministry of Health (MS).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a retrospective cross-sectional observational study to characterize the clinical and&#xD;
      epidemiological profile of patients with spinal muscular atrophy (SMA) 5q types II and III,&#xD;
      in follow-up at the Brazilian Unified Public Health System (SUS). This study aims to provide&#xD;
      baseline data, which in the future may be used by the Brazilian Ministry of Health (MS) to&#xD;
      assess the effectiveness of nusinersen. The clinical and epidemiological data will be&#xD;
      collected from patients´ medical records, such as the score for the Hammersmith Functional&#xD;
      Motor Scale - Expanded (HFMSE) and the Revised Upper Limb Module (RULM) at baseline, the WHO&#xD;
      motor milestones at baseline, disease duration, age at the time of disease diagnosis, age at&#xD;
      the time of disease screening, SMN2 (gene copy number), history of hospitalizations, history&#xD;
      and characterization of previous surgical procedures, treatment dosage used, patient&#xD;
      caregiver´s profile (ie, a family member or companion, who is responsible for taking care of&#xD;
      the patient for most of the time). Other variables of interest that will also be collected&#xD;
      are patient´s age and gender, geographic distribution, attending physician expertise and care&#xD;
      structure where the patients were treated. The data acquisition will be performed using a&#xD;
      paper and eletronic CRF (Case report Form). Written informed consent will be obtained from&#xD;
      patients who meet the study elegibility criteria. The study will be performed in Brazilian&#xD;
      public hospitals (centers) that are able to provide the treatment with nusinersen under the&#xD;
      SUS scope. The total sample of patients and number of participating centers will be defined&#xD;
      by the MS - SCTIE (Secretariat of Science, Technology and Strategic Supplies)/ DECIT&#xD;
      (Department of Science and Technology). However, the initial estimation is a sample of 100&#xD;
      patients to be included in 10-15 centers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 27, 2020</start_date>
  <completion_date type="Actual">April 23, 2021</completion_date>
  <primary_completion_date type="Actual">April 23, 2021</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <target_duration>1 Day</target_duration>
  <primary_outcome>
    <measure>Expanded Hammersmith Functional Motor Scale</measure>
    <time_frame>Baseline</time_frame>
    <description>Hammersmith Functional Motor Scale-Expanded (HFMSE) scores range from 0 to 66, with higher scores indicating better motor function.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Revised Upper Limb Module</measure>
    <time_frame>In the inclusion of the study</time_frame>
    <description>Revised Upper Limb Module (RULM) scores range from 0 to 37, with higher scores indicating better function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>WHO motor milestones</measure>
    <time_frame>Unique evaluation at the time of inclusion</time_frame>
    <description>The six World Health Organization (WHO) motor milestones are sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone, and walking alone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease duration</measure>
    <time_frame>At the time of inclusion in the study</time_frame>
    <description>Time between diagnosis and age at inclusion in the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical features</measure>
    <time_frame>Unique evaluation</time_frame>
    <description>SMN2 (gene copy number);</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>History of hospitalizations</measure>
    <time_frame>Documented in the period prior to the inclusion of the study</time_frame>
    <description>Records of need for hospitalizations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>History and characterization of previous surgical procedures</measure>
    <time_frame>In the period prior to the inclusion of the study</time_frame>
    <description>History of comorbidities</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment with nusinersen</measure>
    <time_frame>Registration of the dose used at the time of inclusion in the study</time_frame>
    <description>To undergo intrathecal administration of nusinersen at a dose of 12 mg</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">155</enrollment>
  <condition>Spinal Muscular Atrophy</condition>
  <arm_group>
    <arm_group_label>Treated with nusinersen at SUS</arm_group_label>
    <description>Patients with Spinal Muscular Atrophy (SMA) 5q types II and III treated with nusinersen in the Brazilian Unified Public Health System</description>
  </arm_group>
  <arm_group>
    <arm_group_label>With indication to receive nusinersen at SUS</arm_group_label>
    <description>Patients with Spinal Muscular Atrophy (SMA) 5q types II and III with indication, but not yet receiving nusinersen treatment in the Brazilian Unified Public Health System</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nusinersen Injectable Product</intervention_name>
    <description>The patient´s treatment is provided by SUS. The following dosage scheme of nurinersen is the one approved by ANVISA (Brazilian National Health Surveillance Agency): Nusinersen, 12 mg (5 mL) on days 0 (zero), 14 and 28. A fourth dose will be on day 63 with a maintenance dose once every 4 (four) months. The study will NOT have direct influence on the care received by patients. Data on adherence, interventions, hospitalizations, mechanical ventilation, procedures and adverse events will be obtained from the patients´ medical records.</description>
    <arm_group_label>Treated with nusinersen at SUS</arm_group_label>
    <other_name>Spinraza</other_name>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with Spinal Muscular Atrophy (SMA) 5q types II and III in follow-up in the&#xD;
        Brazilian Unified Public Health System (SUS), undergoing treatment with nusinersen or not.&#xD;
        For each patient included, a first-degree family member or companion responsible for taking&#xD;
        care of the patient for most of the time will also be included, if they agree to&#xD;
        participate in the study.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Patient Eligibility Criteria:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants of both sexes, in any age group, who have a clinical diagnosis of SMA 5q&#xD;
             type II or type III, in follow-up at SUS, undergoing treatment with nusinersen or not&#xD;
&#xD;
          -  Clinical and molecular diagnosis of SMA 5q type II (disease started after 6 months of&#xD;
             age), or Clinical and molecular diagnosis of SMA 5q type III (disease started after 18&#xD;
             months of age)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Refusal to provide written informed consent (either the patient or a legal&#xD;
             representative)&#xD;
&#xD;
          -  Symptom onset after 19 years of age&#xD;
&#xD;
          -  Need for invasive ventilatory support for 16 hours or more per day for more than 21&#xD;
             consecutive days&#xD;
&#xD;
          -  Be participating or have participated in another clinical study aimed at specific&#xD;
             treatment of SMA 5q other than with the drug nusinersen&#xD;
&#xD;
          -  Having undergone treatment with gene therapy&#xD;
&#xD;
        Caretaker Eligibility Criteria:&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
        • First-degree family member or companion responsible for taking care of the patient with&#xD;
        clinical diagnosis of SMA 5q type II or type III&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Illiteracy&#xD;
&#xD;
          -  Refusal to participate in the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Months</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Otávio Berwanger, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Hospital Israelita Albert Einstein</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Vanessa Teich, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Hospital Israelita Albert Einstein</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Edmar Zanoteli, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Sao Paulo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Elice Batista, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital Israelita Albert Einstein</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universidade Federal de Minas Gerais - Hospital das Clínicas</name>
      <address>
        <city>Belo Horizonte</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clínicas da Universidade Estadual de Campinas - Unicamp</name>
      <address>
        <city>Campinas</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Associação Hospitalar de Prot Infancia Dr Raul Carneiro - Hospital Infantil Pequeno Príncipe</name>
      <address>
        <city>Curitiba</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infantil Dr. Albert Sabin</name>
      <address>
        <city>Fortaleza</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Clínicas de Porto Alegre</name>
      <address>
        <city>Porto Alegre</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Pedro Ernesto</name>
      <address>
        <city>Rio De Janeiro</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Puericultura e Pediatria Martagão Gesteira da Universidade Federal do rio de Janeiro - UFRJ</name>
      <address>
        <city>Rio De Janeiro</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clínicas da Faculdade de Medicina de São Paulo - HCFMUSP</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universidade Federal de São Paulo</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>April 23, 2021</last_update_submitted>
  <last_update_submitted_qc>April 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Hospital Israelita Albert Einstein</investigator_affiliation>
    <investigator_full_name>Otavio Berwanger</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>Spinal Muscular Atrophy</keyword>
  <keyword>Spinal Muscular Atrophy type II</keyword>
  <keyword>Spinal Muscular Atrophy type III</keyword>
  <keyword>Mutation in SMN1</keyword>
  <keyword>Nusinersen</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>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04404764
org study id: 27245419.0.0000.5259
nct id: NCT04404764
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study aims to characterize the clinical-epidemiological profile and baseline
      characteristics of patients with spinal muscular atrophy (SMA) 5q types II and III in
      follow-up at the Brazilian Unified Public Health System (SUS). The study data will be based
      on patients´ medical records from several Brazilian public hospitals, which will be defined
      by the Brazilian Ministry of Health (MS).
This is a retrospective cross-sectional observational study to characterize the clinical and
      epidemiological profile of patients with spinal muscular atrophy (SMA) 5q types II and III,
      in follow-up at the Brazilian Unified Public Health System (SUS). This study aims to provide
      baseline data, which in the future may be used by the Brazilian Ministry of Health (MS) to
      assess the effectiveness of nusinersen. The clinical and epidemiological data will be
      collected from patients´ medical records, such as the score for the Hammersmith Functional
      Motor Scale - Expanded (HFMSE) and the Revised Upper Limb Module (RULM) at baseline, the WHO
      motor milestones at baseline, disease duration, age at the time of disease diagnosis, age at
      the time of disease screening, SMN2 (gene copy number), history of hospitalizations, history
      and characterization of previous surgical procedures, treatment dosage used, patient
      caregiver´s profile (ie, a family member or companion, who is responsible for taking care of
      the patient for most of the time). Other variables of interest that will also be collected
      are patient´s age and gender, geographic distribution, attending physician expertise and care
      structure where the patients were treated. The data acquisition will be performed using a
      paper and eletronic CRF (Case report Form). Written informed consent will be obtained from
      patients who meet the study elegibility criteria. The study will be performed in Brazilian
      public hospitals (centers) that are able to provide the treatment with nusinersen under the
      SUS scope. The total sample of patients and number of participating centers will be defined
      by the MS - SCTIE (Secretariat of Science, Technology and Strategic Supplies)/ DECIT
      (Department of Science and Technology). However, the initial estimation is a sample of 100
      patients to be included in 10-15 centers.
observational model: Cohort
time perspective: Cross-Sectional
measure: Expanded Hammersmith Functional Motor Scale
time frame: Baseline
description: Hammersmith Functional Motor Scale-Expanded (HFMSE) scores range from 0 to 66, with higher scores indicating better motor function.
measure: Revised Upper Limb Module
time frame: In the inclusion of the study
description: Revised Upper Limb Module (RULM) scores range from 0 to 37, with higher scores indicating better function.
measure: WHO motor milestones
time frame: Unique evaluation at the time of inclusion
description: The six World Health Organization (WHO) motor milestones are sitting without support, standing with assistance, hands and knees crawling, walking with assistance, standing alone, and walking alone.
measure: Disease duration
time frame: At the time of inclusion in the study
description: Time between diagnosis and age at inclusion in the study
measure: Clinical features
time frame: Unique evaluation
description: SMN2 (gene copy number);
measure: History of hospitalizations
time frame: Documented in the period prior to the inclusion of the study
description: Records of need for hospitalizations
measure: History and characterization of previous surgical procedures
time frame: In the period prior to the inclusion of the study
description: History of comorbidities
measure: Treatment with nusinersen
time frame: Registration of the dose used at the time of inclusion in the study
description: To undergo intrathecal administration of nusinersen at a dose of 12 mg
arm group label: Treated with nusinersen at SUS
description: Patients with Spinal Muscular Atrophy (SMA) 5q types II and III treated with nusinersen in the Brazilian Unified Public Health System
arm group label: With indication to receive nusinersen at SUS
description: Patients with Spinal Muscular Atrophy (SMA) 5q types II and III with indication, but not yet receiving nusinersen treatment in the Brazilian Unified Public Health System
intervention type: Drug
intervention name: Nusinersen Injectable Product
description: The patient´s treatment is provided by SUS. The following dosage scheme of nurinersen is the one approved by ANVISA (Brazilian National Health Surveillance Agency): Nusinersen, 12 mg (5 mL) on days 0 (zero), 14 and 28. A fourth dose will be on day 63 with a maintenance dose once every 4 (four) months. The study will NOT have direct influence on the care received by patients. Data on adherence, interventions, hospitalizations, mechanical ventilation, procedures and adverse events will be obtained from the patients´ medical records.
arm group label: Treated with nusinersen at SUS
other name: Spinraza
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 6 Months
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Otávio Berwanger, PhD
role: Study Director
affiliation: Hospital Israelita Albert Einstein
last name: Vanessa Teich, PhD
role: Study Chair
affiliation: Hospital Israelita Albert Einstein
last name: Edmar Zanoteli, PhD
role: Study Chair
affiliation: University of Sao Paulo
last name: Elice Batista, PhD
role: Principal Investigator
affiliation: Hospital Israelita Albert Einstein
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Brazil
responsible party type: Principal Investigator
investigator affiliation: Hospital Israelita Albert Einstein
investigator full name: Otavio Berwanger
investigator title: Director
mesh term: Muscular Atrophy
mesh term: Muscular Atrophy, Spinal
mesh term: Atrophy
sharing ipd: No