Chinese Regional Spinal Muscular Atrophy Patient Registration Study

• ClinicalTrials.gov Identifier: NCT05631418
• Recruitment Status: Recruiting
• First Posted: November 30, 2022
• Last Update Posted: November 30, 2022
• Sponsor: The Children's Hospital of Zhejiang University School of Medicine
• Information provided by (Responsible Party): Shanshan Mao, The Children's Hospital of Zhejiang University School of Medicine

Study Description

Brief Summary:

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.

Condition or disease
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 Design

• Study Type: Observational [Patient Registry]
• Estimated Enrollment: 300 participants
• Observational Model: Cohort
• Time Perspective: Other
• Target Follow-Up Duration: 3 Years
• Official Title: The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health
• Estimated Study Start Date: December 2022
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2026

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. World Health Organization (WHO) motor milestone change [ Time Frame: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
   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.
2. Hammersmith Infant Neurological Examination-2 (HINE-2) scale score change [ Time Frame: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
   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.
3. Self-reporting/Caregivers' reporting collection [ Time Frame: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
   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.)
4. Motor function evalution-Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders(CHOP INTEND) scale [ Time Frame: treated/untreated: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
   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.
5. Motor function evalution-Hammersmith Functional Motor Scale-Expanded(HFMSE) scale [ Time Frame: treated/untreated: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
   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.
6. Motor function evalution-Revised Upper Limb Module(RULM) scale [ Time Frame: treated/untreated: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
   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.
7. Motor function evalution change-6 minutes walking test(6MWT) [ Time Frame: treated/untreated: baseline, 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
   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.)
8. Yearly changes of incidence and morbi-mortality-vital events [ Time Frame: every year for 3 years ]
   Events of newly diagnosis, hospitalizations, recurrent infections, fractures, complications and death.
9. Change from baseline respiratory function [ Time Frame: baseline(before treatment), 1 year, 2 year, 3 year ]
   Onset of respiratory support or change in the mode and time (including intubations).
10. Change from baseline digestive-nutritional function [ Time Frame: baseline(before treatment), 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
    Digestive events, onset of nutritional support or change in the mode and time and special intervention.
11. Change from baseline spinal scoliosis Cobb angle [ Time Frame: baseline(before treatment), 1 year, 2 year, 3 year ]
    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.

Secondary Outcome Measures :

1. Pulmonary function [ Time Frame: baseline(before treatment), 1 year, 2 year, 3 year ]
   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.
2. Cardiological function monitoring [ Time Frame: baseline(before treatment), 1 year, 2 year, 3 year ]
   Conventional echocardiography will be evaluated to monitor the patients' cardiac function.
3. Body composition measurement-Lean body mass [ Time Frame: baseline(before treatment), 1 year, 2 year, 3 year ]
   Lean body mass will be measured in patients older than three years by DXA or Inbody device at least once a year.
4. Body composition measurement-Fat mass [ Time Frame: baseline(before treatment), 1 year, 2 year, 3 year ]
   Fat mass will be measured in patients older than three years by DXA or Inbody device at least once a year.
5. Biomarkers [ Time Frame: baseline(before treatment), 0.5 year, 1 year, 1.5 year, 2 year, 2.5 year, 3 year ]
   Change of biomarkers: such as Neurofilaments.
6. Patients and caregivers' quality of life [ Time Frame: baseline(before treatment), 1 year, 2 year, 3 year ]
   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.

Biospecimen Retention:   Samples With DNA

Genomic DNA may be extracted from the whole blood samples of the patients to carry out the genetic testing.

Eligibility Criteria

• Ages Eligible for Study: up to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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.

Contacts and Locations

Contacts

Contact: Shanshan Mao, MD; 19558233981; 6307003@zju.edu.cn

Locations

China

The Children's Hospital, Zhejiang University School of Medicine; Recruiting

Hangzhou, China, 310052

Contact: Shanshan Mao, MD 19558233981 6307003@zju.edu.cn

Sponsors and Collaborators

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

More Information

• Responsible Party: Shanshan Mao, Director, The Children's Hospital of Zhejiang University School of Medicine
• ClinicalTrials.gov Identifier: NCT05631418
• Other Study ID Numbers: CHZhejiang
• First Posted: November 30, 2022
• Last Update Posted: November 30, 2022
• Last Verified: November 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shanshan Mao, The Children's Hospital of Zhejiang University School of Medicine:

Spinal Muscular Atrophy; long-term follow-up; quality of life; disease-modifying treatment; clinical efficacy; disease prognosis; newborn screening

Additional relevant MeSH terms:

Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical