Chinese Regional Spinal Muscular Atrophy Patient Registration Study

The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health

The primary objectives of this study are to obtain clinically meaningful data on the survival, outcomes, prognosis and treatment effect of all the patients with spinal muscular atrophy (SMA) 5q types 1 to 3 (according to international classification), being followed in the Children's Hospital, Zhejiang University School of Medicine since October 2019. The registry will collect retrospectively and prospectively the longitudinal data of the long-term follow-up for children patients, under real life conditions of current medical practice, in order to document the clinical evolution of patients (survival, motor, respiratory, orthopedic and nutritional and so on), the conditions of use of the treatments, the mortality rates of treated and untreated patients, the tolerance of the treatments, adverse events.

Study Overview

• Status: Withdrawn
• Conditions: Recruitment

Detailed Description

The detailed objectives of this study included but not be limited to the following aspects:

1. to collect and describe overall demographic, familial, clinical, biological, and genetic characteristics of patients with 5qSMA diagnosed and treated in regions of China, by the type of SMA (type 1,2, and 3);
2. to study the impact of proactive and symptomatic medical interventions (such as bracing) and medications (disease-modifying treatment, anti-infectious, digestive, nutritional supplements, ect.) in the evolution of patients;
3. to study the long-term evolution (survival, motor and respiratory functions, spinal shape, growth and nutritional function) of 5qSMA in treated and untreated populations, by new available therapies;
4. to study the incidence and mortality rate of 5qSMA in treated and untreated populations;
5. to identify and document the different therapeutic strategies by sub-populations and by discontinuation or follow-up of treatments;
6. to evaluate prognostic factors of responses to different drug therapies;
7. to study the tolerance of treatments by type of treatments, by type of SMA and overall tolerance (including adverse events);
8. to help popularize newborn screening for SMA and pre-symptom treatment among Chinese population;
9. to get knowledge of the probable costs of care for 5qSMA patients in different groups (disease types, ages);
10. to provide needful elements to evaluate the health care costs for the disease;
11. to study the autonomy and the quality of life of patients depending on different therapies and the impact on patients' caregivers;
12. to help facilitate development of basic research on SMA in the conduct of trials on new treatment.

• Study Type: Observational

Contacts and Locations

Study Locations

• China
  • Hangzhou, China, 310052
    • The Children's Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Genetically confirmed 5qSMA patients through 1 to 3 types younger than 18 years old followed in our hospital since October 2019 with or without disease-modifying treatment.

Description

Inclusion Criteria:

1. Genetically confirmed 5qSMA patients through 1 to 3 types younger than 18 years old followed in our hospital since October 2019;
2. For prospective study: inform consent form signed by patient;
3. Not combined with any other genetic and metabolic diseases;

Exclusion Criteria:

1. Other type of SMA (not 5q).
2. Under guardianship or curatorship.
3. Unable to understand or cooperate with the study.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
World Health Organization (WHO) motor milestone change	Treated and untreated patients with SMA Type 1-3: change of WHO motor milestone from baseline to 3 years to track the patients' motor functional development/status. World Health Organization motor milestone score ranges from 0 to 18. The higher the score is, the better the motor function is.	baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Hammersmith Infant Neurological Examination-2 (HINE-2) scale score change	Treated and untreated patients with SMA Type 1-3: change of HINE-2 scale score from baseline to 3 years to help track the patients' motor functional development/status. The HINE-2 scale score ranges from 0 to 26. The higher the score is, the better the motor function is.	baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Self-reporting/Caregivers' reporting collection	Treated and untreated patients with SMA Type 1-3: motor function change acquired from patients themselves and their caregivers. (Subjective reports were collected through interviews and no evaluation scale was used here.)	baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Motor function evalution-Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders(CHOP INTEND) scale	For children ≤ 2 years: change of CHOP INTEND scale score. The CHOP INTEND scale score ranges from 0 to 64. The higher the score is, the better the motor function is.	treated/untreated: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Motor function evalution-Hammersmith Functional Motor Scale-Expanded(HFMSE) scale	For children older than 2 years, ambulatory or not: Change of HFMSE scale score. The scale score ranges from 0 to 66. The higher the score is, the better the motor function is.	treated/untreated: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Motor function evalution-Revised Upper Limb Module(RULM) scale	For children children older than 6 years, ambulatory or not: Change of RULM (Revised Upper Limb Module) scale score. The scale score ranges from 0 to 37. The higher the score is, the better the motor function is.	treated/untreated: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Motor function evalution change-6 minutes walking test(6MWT)	For ambulatory individuals: added the change of 6MWT from baseline to 3 years to test exercise endurance. (The walking distance within 6 minutes is taken as the evaluation index, and there's no specific score range.)	treated/untreated: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Yearly changes of incidence and morbi-mortality-vital events	Events of newly diagnosis, hospitalizations, recurrent infections, fractures, complications and death.	every year for 3 years
Change from baseline respiratory function	Onset of respiratory support or change in the mode and time (including intubations).	baseline(before treatment), 1 year, 2 year, 3 year
Change from baseline digestive-nutritional function	Digestive events, onset of nutritional support or change in the mode and time and special intervention.	baseline(before treatment), 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Change from baseline spinal scoliosis Cobb angle	Onset of spinal deformity, or increment of over 5° in the Cobb angle (examination in supine position or in the upright position, with or without brace, with or without implant (surgery), and the change of the bone mineral density in lumbar.	baseline(before treatment), 1 year, 2 year, 3 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary function	Pulmonary Function Test （PFT）will be evaluated at least once per year for children > 5 years, by specifying the posture of realization of the test, lying vs sitting.	baseline(before treatment), 1 year, 2 year, 3 year
Cardiological function monitoring	Conventional echocardiography will be evaluated to monitor the patients' cardiac function.	baseline(before treatment), 1 year, 2 year, 3 year
Body composition measurement-Lean body mass	Lean body mass will be measured in patients older than three years by DXA or Inbody device at least once a year.	baseline(before treatment), 1 year, 2 year, 3 year
Body composition measurement-Fat mass	Fat mass will be measured in patients older than three years by DXA or Inbody device at least once a year.	baseline(before treatment), 1 year, 2 year, 3 year
Biomarkers	Change of biomarkers: such as Neurofilaments.	baseline(before treatment), 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year
Patients and caregivers' quality of life	Questionary as the "PedsQL Child report/PedsQL parent report concerning child" will be used to evaluate patient's quality of life. The Pediatric Quality of Life Inventory Measurement Models (PedsQLTM) is used for this evalution. The minimum score is 0 and no specific maximum score of this scale. The higher the score is, the higher the quality of life is.	baseline(before treatment), 1 year, 2 year, 3 year

Collaborators and Investigators

• Sponsor: The Children's Hospital of Zhejiang University School of Medicine
• Investigators: Principal Investigator: Shanshan Mao, MD, The Children's Hospital of Zhejiang University School of Medicine

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2022
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): December 1, 2026

Study Registration Dates

• First Submitted: October 23, 2022
• First Submitted That Met QC Criteria: November 20, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Estimate): February 23, 2023
• Last Update Submitted That Met QC Criteria: February 22, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: quality of life; long-term follow-up; Spinal Muscular Atrophy; clinical efficacy; disease-modifying treatment; disease prognosis; newborn screening
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Atrophy; Muscular Atrophy
• Other Study ID Numbers: CHZhejiang

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No