Longitudinal Data Collection in Pediatric and Adult Patients With Spinal Muscular Atrophy in Latin America (RegistrAME)

Protocol-LATAM RegistrAME: Longitudinal Data Collection in Pediatric and Adult Patients With Spinal Muscular Atrophy in Latin America - a Regional Registry

The natural history of SMA patients has changed, due to the improvements in treatment and technological advances. The systematic collection of data from routine clinical practice in multiple Latin American countries, harmonized to an internationally aligned core data set, is important to advancing the understanding the natural history of disease in the region and the influence of different drug treatments on patient outcomes. These data are critical to improving the care of these patients. So far, clinical trials regarding therapeutic approaches for SMA patients only cover a subgroup of the broad spectrum of severity of SMA. Thus, there is a strong need to monitor the full range of treated and untreated SMA patients in a real-world context.The aim of this study is to set up a regional healthcare provider (HCP) entered registry. The planned SMA registry will provide an online platform to collect longitudinal data on SMA patients across Latin America to achieve a better understanding of the clinical characteristics of SMA patients, the natural history of the disease, the use of DMTs and patients' outcomes, as well as to support further research projects and regional data generation.

Study Overview

• Status: Active, not recruiting
• Conditions: Spinal Muscular Atrophy

Detailed Description

This is a retrospective and prospective, multicenter non-randomized registry in Latin America. The variables included in the RegistrAME registry are based on the core items defined by the TREAT-NMD for SMA registries and the RegistrAME steering committee consensus. Items such as demographic characteristics, date of genetic test result, clinical diagnosis, functional status and pulmonary function, among others, are included in RegistrAME. The RegistrAME registry will allow the inclusion of retrospective clinical data in those centers where natural history studies of for spinal muscular atrophy are currently being conducted. RegistrAME will also offer a standardized structure for prospective data collection in all centers. The current aim of this registry is to include centres in LATAM meeting the structural and personnel requirements for performing the planned regular registry-related investigations. These reference centers in LATAM (Latin America) will be selected from COEs which 1) have the potential to enroll and make the proper patient follow up, 2) have experience in treating SMA, and 3) have experience in conducting clinical trials. An electronic Case Report Form (e-CRF) will be created by the ARO (Academic Research Organization) from Hospital Albert Einstein, using REDCap (Research Electronic Data Capture). The electronic Case Report Form (e-CRF) created to meet international standards for data protection and quality management, and to harmonize the platform with those currently used by other countries. No interventions will be performed in this study, the RegistrAME is observational study non-randomized, international multicenter study (Registration of patients in Latin America). Data collection aims to gather as much information as possible regarding the clinical profile of patients, interventions performed in the routine of care and clinical evolution over time (Real World Evidence-RWE). After confirmation of eligibility and informed consent, patients will undergo medical evaluation, and then retrospective data collection (when possible and limited to 6 months before the patient inclusion in the study), baseline data and continuation of longitudinal data collection will be started. Data entry is planned to be performed every carried out at intervals of 4 to 6 months (according to the type of SMA), depending on the regular healthcare planning of each clinical site. The study will assess disease progression, both the natural history of the disease and the effectiveness of different SMA specific drug treatments on patient outcomes. Duration of disease, survival with or without ventilatory support, motor function, pulmonary function, developmental milestones achieved, growth parameters, orthopedic symptoms, functional assessments (CHOP-INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders), HINE-2 (Hammersmith Infant Neuromuscular Examination - session 2), HFMSE (Hammersmith Motor Functional Scale Expanded), RULM (Revised Upper Limb Module), and 6MWT (The six minute walking test)) will be analyzed depending on the functional capacity of the patients and 5q SMA type over time.

• Study Type: Observational
• Enrollment (Actual): 361

Contacts and Locations

Study Locations

• Argentina
  • Córdoba, Argentina
    • Clínica Universitaaria Reina Fabiola
  • Mendoza, Argentina
    • Hospital Pediátrico Humberto Notti
  • Caba
    • Buenos Aires, Caba, Argentina, Potosi 4135
      • Hospital Italiano de Buenos Aires
    • Buenos Aires, Caba, Argentina
      • Hospital de Pediatria J.P.Garrahan
  • Rivadavia 4951 PB 2 Caballito
    • Buenos Aires, Rivadavia 4951 PB 2 Caballito, Argentina, 1424
      • Private Office
• Brazil
  • BA
    • Salvador, BA, Brazil
      • HUPES - Escola Bahiana de Medicina e Saúde Pública
  • MG
    • Belo Horizonte, MG, Brazil
      • UFMG - Universidade Federal de Minas Gerais - Hospital das Clínicas
  • Paraná
    • Curitiba, Paraná, Brazil
      • Hospital Infantil Pequeno Príncipe
  • RJ
    • Rio De Janeiro, RJ, Brazil
      • Instituto de Puericultura e Pediatria Martagão Gesteira da UFRJ
  • RS
    • Porto Alegre, RS, Brazil
      • HCPA - Hospital de Clinicas de Porto Alegre
  • SP
    • Campinas, SP, Brazil
      • Unicamp - Hospital de Clínicas da Universidade Estadual de Campinas
    • São Paulo, SP, Brazil
      • Hospital Israelita Albert Einstein
    • São Paulo, SP, Brazil
      • Instituto da Criança do Hospital das Clínicas de São Paulo - FMUSP
• Chile
  • Santiago, Chile
    • Clinica MEDS La Dehesa
• Colombia
  • Bogotá, Colombia
    • Fundação Hospital da Misericórdia
  • Bogotá, Colombia
    • Instituto Roosevelt Pontifícia Universidade Javeriana
• Mexico
  • Monterrey, Mexico
    • Hospital Christus Muguerza Alta Especialidade
• Uruguay
  • Montevideo, Uruguay
    • Centro Hospitalario Pereira Rossell, Facultad de Medicina- Universidad de la Republica

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 weeks and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with SMA 5q Types 1, 2, 3 and 4 (with and without disease-modifying treatment) of all ages and both sexes.

Description

Inclusion Criteria:

• Genetically confirmed 5q SMA patients at all ages;
• Consent to participate in the study, expressed by the patient or responsible or legal guardian of the pediatric patient/ responsible or legal guardian of the patient with cognitive impairment of understanding the registration protocol.

Exclusion Criteria:

• Patients without a genetic diagnosis confirming SMA 5q;
• Other types of SMA (non 5q SMA);
• Patients who do not accept to participate in the observational study;
• Patients without the legal capacity who are unable to understand the nature, significance and consequences of participating in the registry, or, in such cases, without a legal or responsible guardian.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Type 1 SMA (with and without use of disease-modifying treatment (DMTs)); Participants of both sexes who presented signs and symptoms of Spinal Muscular Atrophy before six months of age and have a genetic report confirming 5q SMA.; No interventions will be performed in this study (RegistrAME is observational study (retrospective and prospective) non-randomized, international multicenter study- Registration of patients in Latin America).; Data collection aims to gather as much information as possible regarding the clinical profile of patients, interventions performed in the routine of care and clinical evolution over time (Real World Evidence-RWE).; The planned SMA registry will provide an online platform to collect longitudinal data on SMA patients across Latin America to achieve a better understanding of the clinical characteristics of SMA patients, the natural history of the disease and the use of DMTs (on participants who are using DMTs).
Type 2 SMA (with and without disease-modifying treatment (DMTs)); Participants of both sexes who presented signs and symptoms of Spinal Muscular Atrophy starting between six and eighteen months of age and have a genetic report confirming 5q SMA.; No interventions will be performed in this study (RegistrAME is observational study (retrospective and prospective) non-randomized, international multicenter study- Registration of patients in Latin America).; Data collection aims to gather as much information as possible regarding the clinical profile of patients, interventions performed in the routine of care and clinical evolution over time (Real World Evidence-RWE).; The planned SMA registry will provide an online platform to collect longitudinal data on SMA patients across Latin America to achieve a better understanding of the clinical characteristics of SMA patients, the natural history of the disease and the use of DMTs (on participants who are using DMTs).
Type 3 SMA (with and without disease-modifying treatment (DMTs)); Participants of both sexes who presented the first signs and symptoms of Spinal Muscular Atrophy starting after eighteen months of age and have a genetic report confirming 5q SMA.; No interventions will be performed in this study (RegistrAME is observational study (retrospective and prospective) non-randomized, international multicenter study- Registration of patients in Latin America).; Data collection aims to gather as much information as possible regarding the clinical profile of patients, interventions performed in the routine of care and clinical evolution over time (Real World Evidence-RWE).; The planned SMA registry will provide an online platform to collect longitudinal data on SMA patients across Latin America to achieve a better understanding of the clinical characteristics of SMA patients, the natural history of the disease and the use of DMTs (on participants who are using DMTs).
Type 4 SMA (with and without disease-modifying treatment (DMTs)); Participants of both sexes and that the first symptoms of Spinal Muscular Atrophy appeared from the second or third decade of life and have a genetic report confirming 5q SMA.; No interventions will be performed in this study (RegistrAME is observational study (retrospective and prospective) non-randomized, international multicenter study- Registration of patients in Latin America).; Data collection aims to gather as much information as possible regarding the clinical profile of patients, interventions performed in the routine of care and clinical evolution over time (Real World Evidence-RWE).; The planned SMA registry will provide an online platform to collect longitudinal data on SMA patients across Latin America to achieve a better understanding of the clinical characteristics of SMA patients, the natural history of the disease and the use of DMTs (on participants who are using DMTs).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the natural history of the disease (5q SMA in patients in Latin America) in a real-life context.	Characterization and description the evolution of the patient's condition over the time of data collection from the registry, to describe the natural history of the disease in a real-life context.	24 months (Study duration time)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease characteristics at first diagnosis.	Early signs and symptoms leading to clinical diagnosis of SMA	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of disease.	Time interval between the age of appearance of the first signs and symptoms to the current age	24 months (Study duration time)
Time from SMA symptom onset until genetic diagnosis.	To verify heterogeneity of access resources to genetic diagnosis.	Baseline
Motor milestones over time.	Motor functions (unable to sit, sitting without support, walking with support; standing without Support; walking independently) will be evaluated over time.	24 months
Expanded Hammersmith Functional Motor Scale	Hammersmith Functional Motor Scale-Expanded (HFMSE) scores range from 0 to 66,	24 months
Revised Upper Limb Module	Revised Upper Limb Module (RULM) scores range from 0 to 37, with higher scores indicating better function.	24 months
Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders Scale (CHOP-INTEND)	CHOP-INTEND (Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders) scores range from 0 to 64 with higher scores indicating better function.	24 months
Gain and loss of motor function	Analyze throughout the study "Shift up (gained motor function)", "No change" and "Shift down" (loss of motor function) over time, in the different types of 5qSMA with and without disease-modifying treatment.	24 months (Study duration time)
History of hospitalizations	Records of need for hospitalizations	24 months (Study duration time)
History and characterization of previous surgical procedures and need for surgery	History of comorbidities	24 months (Study duration time)
Utilization of DMTs - Disease Modifying Treatments	History of use or non-use of DMTs	24 months (Study duration time)
Use of Medications	Analysis of the history of drugs used in the clinical routine of patients	24 months (Study duration time)
Pulmonary Function	Frequency and length of time of ventilatory support use	24 months (Study duration time)

Collaborators and Investigators

• Sponsor: Hospital Israelita Albert Einstein
• Collaborators: Biogen
• Investigators: Study Director: Otávio Berwanger, PhD, Hospital Albert Einstein; Study Director: Henrique Fonseca, PhD, Hospital Albert Einstein

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Estimated): August 30, 2024
• Study Completion (Estimated): January 30, 2025

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: July 24, 2022
• First Posted (Actual): July 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Nusinersen; Spinal Muscular Atrophy 1; Spinal Muscular Atrophy 2; Spinal Muscular Atrophy 3; Spinal Muscular Atrophy 4; SMN1 gene; onasemnogene abeparvovec; Small molecule drug
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Spinal Cord Diseases; Motor Neuron Disease; Muscular Atrophy; Atrophy; Muscular Atrophy, Spinal
• Other Study ID Numbers: Protocol-LATAM RegistrAME

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No